Laboratory of Bacterial Genetics

Prof. Valery N.Danilenko, Dr.Biol.Sci. (Head)

Tel:  (499) 135-41-94 (499) 135-30-56

e-mail: valerid(at)vigg.ru

 

Laboratory of genetics of microorganisms conducts research in the fields of human microbiome and tuberculosis.

Research topics

-Microbial population genetics of human ecosystems: our studies encompass probiotic commensal bacteria such as lactobacilli and bifidobacteria as well as latent tuberculosis infection;

-Interaction (communication) between the intestinal microbiota and the brain;

-The role of signal transduction systems mediated by serine-threonine protein kinases (STPK) as well as the stress responsive system of toxin-antitoxin (TA) in promoting the adaptation of bacteria to different ecological niches of the human body;

-Identification and characterization of genetic polymorphisms in STPK and TA genes of bacteria isolated from various ethno-regional human populations;

-The search for new genetic mechanisms of interaction between commensal/non-commensal bacteria and the host organism.

-Development of biological targets and test-systems for selecting new potential therapeutic candidate molecules.

Laboratory structure:

 



1. Group of genetics and comparative genomics of mycobacteria

2. Group of genetics and comparative genomics of lactobacilli

3. Group of genetics and comparative genomics of bifidobacteria

4. Group of microbial endocrinology and the regulatory networks underlying host-microbiota    interactions

5. Development of biological targets and test systems

6. Bioinformatics group

 


Brain – gut – microbiota communication in health and disease.

In the last few years, studying the human microbiome has become a global trend in biomedicine: discovering the bidirectional communication established between gut microbiota and the brain has led to a paradigm shift in understanding the functioning of nervous, endocrine and immune systems. Gut commensal bacteria can synthesize a wide variety of substances involved in neuromodulation including serotonin, dopamine, adrenaline, gamma-aminobutyric acid, short-chain fatty acids etc. In this regard, a new discipline known as microbial endocrinology has emerged.

For the last five years, the laboratory of genetics of microorganisms, Vavilov Institute of General Genetics, Russian Academy of Sciences, has been conducting human microbiome research using different approaches: molecular genetics, genomics and metagenomics. Our ultimate objective is to reveal the mechanisms of interaction between the probiotic bacteria (lactobacilli, bifidobacteria and others) and the host in the absence of stress and under extreme conditions. Our main focus is on direct as well as indirect interaction of bacteria with both the peripheral and central immune systems. One approach is to build gene catalogues containing genes involved in neuromodulation and their orthologues; the next step is to write a program for analyzing sequenced gut metagenomes and revealing signatures (gene compositions and bacterial species to which they belong) in the GIT of healthy people compared to those with depression and cognitive disorders. Sets of instruments for diagnosis and prevention of neurodegenrative disorders are being developed in our laboratory. We are also engaged in the selection of Lactobacillus and Bifidobacterium strains containing gene compositions involved in the synthesis and the production of neuroactive compounds such as gamma-aminobutyric acid, short-chain fatty acids etc. An essential part of our projects is based on creating and maintaining a collection of stool samples and probiotic strains.

Human microbiota biobank

The collection was created in 2009 as a part of two projects:

- Government contract № 02.522.12.2009 from 2008 to 2010, "development of universal starter culture techniques for the application in industrial biotechnology".

- The Russian Foundation for Basic Research № 09-04-13709 from 2009 to 2010, "development of diagnostic test-systems for selecting Bifidobacterium and Lactobacillus strains based on the presence of TA genes promoting adaptation to stress in their genomes".

In the years that followed, the collection was replenished as part of the following projects:

- Government contract, Ministry of Education and Science № 14N08.12.0021 from 2014 to 2015, "Preclinical studies of a probiotic consisting of Bifidobacterium, Lactobacillus and Enterococcus strains, for which genomic sequences are available, for treating nonspecific ulcerative colitis"

- Fundamental research program, Presidium of the Russian Academy of Sciences, from 2014 to 2016, "Fundamental research in the field of biomedical technology", "Development of experimental diagnostic test-systems for species identification and assessment of intra-species diversity of lactobacilli and bifidobacteria in the human intestine using multilocus sequencing". Today, our collection is qualified as a unique Russian collection and is restricted to the use inside our institute. It is considered as basic for creating an interindustrial collection under the aegis of the Federal Agency of Scientific Organizations as part of the consortium "Complex Scientific Research", Human microbiome project.

The human microbiota biobank contains:

-150 human stool samples.

-A collection of Lactobacillus strains belonging to 17 species; the majority of strains belong to 8 species: L. rhamnosus, L. plantarum, L. fermentum, L. casei, L. brevis, L. buchneri, L. helveticus, L. salivarius; 150 strains in total.

-A collection of Bifidobacterium strains belonging to 20 species; 165 strains in total. All bifidobacterial strains were isolated from the gut microbiota of healthy adults and children, living in the central region of Russia.

Lactobacillli and bifidobacteria were screened for the ability gamma-aminobutyric acid (GABA), serotonin, dopamine and other compounds. These properties were found to be species- or strain-specific. Strains with the highest productivity of neuroactive compounds were selected as potential psychobiotics. The genomic sequence of such strains was obtained and deposited in the NCBI database: B. adolescentis 150 (LBHQ00000000); B. angulatum GT 102 (LAHN00000000); L. plantarum 90sk (JXAX00000000); L. brevis 15f (JXCD00000000). Genes involved in production and transport of GABA as well as other neuroactive compounds were identified in the genomes of the sequenced strains.

In case if these collections are lost, they would be impossible to restore. This also applies to the stool samples since the diversity of species and strains and their composition in each sample is unique.

The collection is sustained with the following set of equipment:

-Controlled rate freezer Kryo 360.

-Cryogenic pump LNP4.

-Arpege vessel 170 L.

-Dewar flasks.

-Ultra-low temperature freezer.

-Vacuum freeze dryer.

-Refrigerators and freezers.

-Office appliances.

The biobank is run by a skilled staff that is responsible for freezing the samples and maintaining their long-term viability. Rooms with laminar flow cabinets are available to work with lactobacilli, bifidobacteria and human fecal samples; the rooms apply to safety requirements. Liquid nitrogen is supplied to the biobank every month. A reliable system of power and water supply, as well as ventilation ensure long-term storage of the biological samples.

http://www.microbiome-standards.org/fileadmin/Content/IHMS/_IHMS__Deliverable_Report_D2.2.pdf

The maintenance of the human microbiota biobank is carried out in accordance with certain rules. The following Standard Operation Procedures (SOP) are observed:

1) SOPs and methods of sustaining the viability of samples: monthly subcultivation of samples is used for this purpose.


2) SOPs and quality controlling methods: streaking the samples on agar plates in order to make sure no contamination of the samples have occurred by observing the morphology of the bacterial colonies. PCR of the 16S ribosomal RNA gene is carried out followed by amplicon sequencing for species identification.


3) SOPs and methods of restoring the purity of samples: streaking the samples on agar plates in order to select colonies with typical morphology and other known properties; to confirm the species of the selected colonies, PCR of the 16S ribosomal RNA gene is performed.

6)

7) Methods of replenishing the collection: isolation of microbiota samples (faeces, saliva etc.)

8)

9) Methods of characterizing the samples: species identification by using species specific primers or  amplification fo the 16S ribosomal RNA gene with subsequent sequencing of the yielded amplicon. Identification of probiotic properties of strains: production of neuroactive compounds, GABA, antioxidant molecules, neurotransmitters, bacteriocins, immunomodulatory components. Sequencing and metagenomic analysis of potential probiotics. To isolate fecal samples, standardized methods are used: International Human Microbiome Standards:

10) http://www.microbiome-standards.org/fileadmin/Content/IHMS/_IHMS__Deliverable_Report_D2.2.pdf

Tuberculosis – adequate responses to a new challenge.

For the last ten years, an extensive body of literature dedicated to the mechanisms of occurrence of Multiple Drug Resistance (MDR) and Broad Drug Resistance (BDR) in M. tuberculosis strains as well as to creating new antibiotics and preventive/therapeutic genetically engineered vaccines and their adjuvants against M. tuberculosis strains was published; this emphasizes the complicity of drug resistance in M. tuberculosis, a problem that we has not yet succeeded to solve.

In our laboratory, research aimed at developing new approaches of antibiotic therapy is being carried out; these approaches include the use of mucosal and DNA-vaccines and their adjuvants based on probiotics with immunomodulatory activity. Guidelines for the use of TB drugs, those existing or new, are being developed.

According to WHO’s estimates, approximately 10,4 tuberculosis cases were recorded in 2015 with almost 1,8 million deaths (WHO's Global tuberculosis report, 2016). Although today tuberculosis vaccination is widespread, the incidence remains extremely high due to questioned effectiveness of the BCG vaccine used for global immunization. It varies from 0% to 80% depending on numerous factors, such as age, immune status, etc (Liu J. et al, 2009; Hesseling et al., 2007, Mangtani et al, 2014). Another important problem associated with BCG usage is that it has a high reactogenicity. Besides, BCG can not be used on patients with immunodeficiency and, as shown in recent studies, it lacks effectiveness against pulmonary form of tuberculosis. Therefore, the problem of new TB vaccines development is among the highest priorities in phthisiology. Currently the subunit vaccines are the most promising outlooks (Kaufmann S.H. et al., Int J Infect Dis. 2017, doi: 10.1016/j.ijid.2016.10.018; Méndez-Samperio P., Scand J., Immunol. 2016, 84(4), Pp 204-10). A key challenge in the development of such vaccines is to find the optimal antigenes (Andersen P., Kaufmann S.H., Cold Spring Harb Perspect Med. 2014, 4(6). doi: 10.1101/cshperspect.a018523). The structural elements of M. tuberculosis pathogenicity demonstrate strong antigenicity. M. tuberculosis genome encodes more than 300 of such elements and today they are considered as a basis for the subunit vaccines development (Prozorov et al, 2014; Forrellad et al, 2013). Many of these genes have single nucleotide polymorphisms that accumulated during the evolution. A considerable part of such mutation leads to the amino acid replacement and can affect the structure of protein product and change its properties, including antigenic activity. Today intraspecific diversity of M. tuberculosis is not considered during design of genetically engineered vaccines. Only sequences of the target genes of laboratory strain H37Rv are used. It was found for vaccine M. bovis BCG strain that mutations, arisen during long-term cultivation as a result of microevolution, influence the vaccine’s effectiveness (Brosch R., Proc Natl Acad Sci USA. 2007, 104(13), Pp 5596-601). It is possible that the antigenic activity also varies among different M. tuberculosis strains.

Another promising direction is the development of tuberculosis candidate mucosal vaccine that firstly induces formation of local mucosal immunity. The importance of local anti-TB immunity induction was shown in several studies, in which the intranasal introduction of protective lgA or M. bovis BCG, or pre-treatment of virulent M. tuberculosis with protective lgA led to formation of an effective response to M. tuberculosis (Uranga S. et al., J Vis Exp. 2016, doi: 10.3791/54440; Zimmermann N. et al., EMBO Mol Med. 2016, 8(11), Pp 1325-39; Alvarez N. et al., Malays J Med Sci. 2014, 21(3), Pp 31-7; Alvarez N., BMC Immunol. 2013, Suppl.1-S3). The problems arising from BCG vaccination could be solved by the use of mucosal vaccines, both separate or with the subcutaneous form.

However, today none of the new TB vaccines is used in clinical practice. Often the weakness of such vaccines if the low immunogenicity that implies the use of immunoadjuvants in vaccine’s products. Intranasal probiotic administration also can render adjuvant and immunomodulatory effects, thus increasing the effectiveness of mucosal immune defense. Some probiotic strains, bifidobaceria in particular, can induce production of Th17- and Th1- cytokines (López P. et al., Int J Food Microbiol. 2010, 138(1-2), Pp 157-65), which play crucial role in the mucosal immune response during tuberculosis infection (Uranga S. et al., J Vis Exp. 2016, doi: 10.3791/54440). Hence, intranasal probiotics administration may have an adjuvant effect for the mucosal tuberculosis vaccine and form the protective immunity to virulent strains of M. tuberculosis.

Another serious problem that faces modern phthisiology is the prevalence of strains with multiple and extensive drug resistance. In 2015 there were more than 580 thousands of patients suffering from MDR and XDR tuberculosis. Mutations, affecting structure of a drug target or a drug activator, are crucial for emergence of drug resistance. These strains are so widespread due to the prolonged usage of the same drug set. Bedaquiline has recently became the first in more than 40 years TB drug used in clinics (Chahine E.B., et al., Ann Pharmacother. 2014, 48(1), Pp. 107–115).

In this regard, the development of new TB drugs in of high importance. They must meet certain requirements: a high antimycobacterial activity against both drug-sensitive and MDR M. tuberculosis strains, the presence of a new biotarget and a lack of toxicity.

Nevertheless, in addition to the acquired drug resistance, the intrinsic drug resistance exists that shows low level of antibiotics resistance comparing to the acquired one. When an antibiotic influence M. tuberculosis cell, it activates transcriptional factors that control expression of genes, whose products are able to modify antibiotics or their targets, to reverse transport antibiotics or their active derivatives from M. tuberculosis. In addition, M. tuberculosis cells are capable of constitutive nonspecific reverse transport of antibiotics out of cells due to numerous cellular transporters. The set of genes whose products are involved in the intrinsic drug resistance is defined as resistome.

It is believed that mutations leading to various drugs resistance arise independently, although in some cases the cross-resistance is observed. The cross-resistance arises when the emergence of resistance to one drug leads to the emergence of resistance to other drugs. This phenomenon is triggered by the resistome genes. As described previously, the “cell stress” transcription factors cause the expression of numerous resistome genes, which often results in increased drug resistance of M. tuberculosis cells to several antibiotics classes at once.

The combination of induced, intrinsic, cross-, and drug resistance increases the general level of the pathogen’s drug resistance. Usage of antibiotics in the treatment of concomitant tuberculosis infections or penetration of antibiotics into food can increase M. tuberculosis drug resistance.

The development of high level drug resistance, that combine intrinsic and induced drug resistance and is capable of cross-resistance induction, is one of the most important problems. Its solution will optimize and improve the course of TB treatment. Thus, a complex approach is needed to solve the TB problem. It should include new vaccines development to prevent the disease specifically, and the development of new treatment approaches including the search for new TB drugs.

From 2010 until the present day, the laboratory personnel are conducting research within the framework of contracts with the Ministry of Industry and Trade of Russia, the Ministry of Education and Science of Russia, the RFBR, the RNF, the Russian Academy of Sciences:

Russian Foundation for Basic Research grants

Structural and Functional Characterization of Actinobacterial Serine-Threonine Protein Kinases as Biotargets for Design of Novel Anti-Infective Drugs. (years 2009-2010)

Biotargeted screening of novel anti-infective drugs based on serine-threonine protein kinases of Mycobacterium tuberculosis. (years 2009-2010).

Development of a diagnostic test-system for strains of probiotic bacteria of Bifidobacterium and Lactobacillus genera, carrying toxin-antitoxin systems genes for adaptation to stress conditions. (years 2009-2010).

 

Development of a new test system for screening anti-tuberculosis drugs using Mycobacterium smegmatis as a working model. (years 2011-2012).

 

Study of the functions of aminoglycoside phosphotransferases of Streptomyces rimosus subsp. Rimosus ATCC10970, which accounts for its natural resistance to aminoglycoside antibiotics (years 2017-2019).

Ministry of education and science of Russian Federation

Development of technologies for universal fast-adaptable direct inoculation leavens for biotechnology industry. (years 2008-2010).

Development of new target-specific human and bacterial F0F1 ATP synthases inhibitors. (year 2009-2010)

Preparation of crystals and X-ray diffraction studies of aminoglycoside phosphotransferase type VIII (aphVIII), the key element of test-systems for serine/threonine protein kinases inhibitors screening. (years 2011-2012).

Preclinical studies of a drug based on a complex of bifidobacteria, lactobacilli and enterococci with known genome sequence for treatment of ulcerative colitis. (years 2013-2015).

 

"Preclinical studies of a probiotic consisting of a gluthatione-producing Lactobacillus brevis strain (sequenced genome) for treating drug-induced enteropathy"(years 2016-2018).

 

Preclinical studies of an antituberculous drug based on a synthetic glutamic acid derivative (years 2017-2019)

Ministry of industry and trade of Russian Federation

Preclinical studies of anti-tuberculosis drug, inhibitor of mycobacterial protein kinases. (years 2011-2013).

Preclinical studies of anti-tuberculosis drug, based on semi-synthetic derivatives of usnic acid. (years 2012-2014).

Preclinical studies of a drug based on a selective serine/threonine protein kinase inhibitor for cancer treatment. (years 2013-2015).

Preclinical studies of a drug based on IRAK-4 kinase inhibitor for treatment of autoimmune and chronic inflammatory diseases. (years 2013-2015).

 

Preclinical studies medicament - an inhibitor of glycogen synthase kinase 3 beta, based on N-substituted derivative amrinone for treating type 2 diabetes. (years 2014-2016)РНФ

Complete metagenomic analysis of enteric microbiota in children with autism spectrum disorder: searching for marker gene compositions (years 2017-2019).

Russian Academy of Sciences.

Program of basic research of RAS Presidium “Basic Sciences for Medicine”. Test-system development and inhibitors screening for Streptomyces serine/threonine protein kinase Pk17 – inducers of actinobacterial programmed cell death. (years 2010-2011).

 

Program of basic research of RAS Presidium “Basic research for the development of biomedical technologies”. Development of an experimental sample of diagnostics set for human gut microbiota(years 2014 -2016)

International

RFBR grant NIH (USA-Russia) "Toxins-antitoxins and RpsA in drug resistance and persistence of Mycobacterium tuberculosis" (years 2013-2014).

In the period from 2012 until 2017, the results of research were reported at the following events:

International Human Microbiome Congress, Paris, France, March 19-21, 2012 .

US-RU Workshop “TB in AIDS-Infected Individuals: New Paradigm, Diagnosis and Drug Development” Within US-RU Scientific Forum for Biomedical Research, Central Research Institute of Epidemiology, Moscow, June 28-29, 2012.

US-RU joint workshop “Human Microbiome: Metagenomics, New Biomarkers of Disease, Translational Research in Personalized Medicine” within US-RU Scientific Forum for Biomedical Research Vavilov Institute of General Genetics, Moscow, September 17-18, 2012.

Conference "Postgenomic methods of analysis in biology, laboratory and clinical medicine", Kazan (Privolzhsky) Federal University, Kazan, November 22 - 24, 2012.

Second International Scientific Conference “REGENERATIVE MEDICINE & HEALTHY AGING”, Astana, Kazakhstan, November 1-2, 2012.

International Conference “High-Throughpup Sequencing in Genomics” HSG, Russia, Novosibirsk, 21.07.2013.

«The 5th Congress of European Microbiologists»,Germany, Leipzig, 21.07.2013.

«38th FEBS Congress» Russia, St. Petersburg, 06.07.2013.

"19 Russian-American Symposium on Biotechnology in Industry, Agriculture and Healthcare", USA, Philadelphia, 11.03.2014.

Ural Scientific Forum "Contemporary Problems of Organic Chemistry", Russia, Ekaterinburg, 08.06.2014

International Conference “High-Throughpup Sequencing in Genomics”, Russia, Novosibirsk, 21.07.2013

 

The 5th Congress of European Microbiologists, Germany, Leipzig 21.07.2013

 

38th FEBS Congress, Saint Petersburg, Russia, July 6-11, 2013

International conference dedicated to the 75th anniversary of the Department of Biotechnology and the 20th anniversary of the Institute of Biology and Biotechnology "Contemporary issues of Biotechnology, Nanotechnology and Physico-Chemical Biology" Kazakhstan, Almaty, 11/21/2013

19 Russian-American Symposium on Biotechnology in industry, agriculture and health, Philadelphia, USA , March 11 - 16, 2014

 

Ecoforum, Saint Petersburg, Russia, September 21-24, 2014

 

International Forum "Pharmaceuticals and Medical Products" 2014, Tomsk, Russia, September 23-24, 2014

8th International Biotechnological Forum-Exhibition "RosBioTech 2014" Moscow, Russia, October 27-28, 2014

The 2015 TB SUMMIT European Scientific Conferences, United Kingdom, London, March 23-26, 2015

5th International Human Microbiome Congress - IHMC Congress (IHMC), Luxembourg, 31March – 2 April, 2015

International Military Technical Forum "ARMY-2015" round table "Medical support of the Armed Forces of the Russian Federation in the Arctic", June 16-19, CEC "Patriot", Moscow region, Kubinka

International Scientific Conference on Probiotics and Prebiotics – IPC2015, Budapest, 23rd – 25th June 2015

 

MedChem 2015, 2nd Russian Conference on Medicinal Chemistry, Novosibirsk, Russia, July 5-10, 2015

 

Microbios 2015, Tashkent, Uzbekistan, November 25-27, 2015

Workshop "Scientific cooperation of the Russian Foundation for Fundamental Research and National Institutes of Health of the USA, St. Petersburg, Russia, 04/13/2016

III International Scientific Conference "Genetics and biotechnology of the XXI century: problems, achievements, prospects", dedicated to the 115th anniversary of the birth of Academician A.R. Zhebrak and XI Congress of the Belarusian Society of Geneticists and Breeders, Minsk, 23-25 November 2016

International Congress: Biotechnology: State and Prospects for Development, Moscow, Gostiny Dvor, February 20-22, 2017

Second UK-Russia roundtable discussion “Antimicrobial resistance (AMR): action plans implementation”, Москва, 20-21 февраля 2017

Round table "Microbiota (microbiota) of man in norm and pathology" X International scientific conference "Microbial biotechnologies: fundamental and applied aspects" Minsk, June 7, 2017.

Laboratory achievements

Over the last years, we created a unique technology panel for screening drugs to treat socially significant diseases such as tuberculosis. Hundreds new substances belonging to different classes of drugs were screened (benzodiazepines, benzophtalazines, carboranes, Cyclopentenediones, indolylmaleimides, pyridazines, pyrazoles, quinoxalines, thiazoles, thiazole tetrazines) which allowed selecting candidate molecules for treating infectious diseases including M. tuberculosis as well as other immunological and oncological diseases. As STPK represent a target for many molecular species that are potential drugs, the laboratory personnel set up an efficacious testing panel to screen for serine-threonine protein kinase inhibitors. A collection of probiotic Lactobacillus and Bifidobacterium strains was created and characterized to be used for developing pharmaceuticals with immunomodulatory, antioxidant and anti-inflammatory properties as well as adjuvants and vaccines of different classes.

For the first time, type II toxin-antitoxin systems of lactobacilli and bifidobacteria were identified and characterized yielding enough knowledge to develop diagnosticums for strain identification in human gut metagenomes. The immunomodulatory activity exhibited by Lactobacillus and Bifidobacterium strains was shown to be strain-specific. The genomes of 20 Lactobacillus strains, 10 Bifidobacterium strains, 5 Streptomyces strains and 20 Tuberculosis strains were sequenced and annotated. A genotyping method based on polymorphisms in type II toxin-antitoxin and virulence genes of M. tuberculosis was developed. 3D crystal structure of the aminoglycoside transferase aph VIII (deposited in PDB under the number 4Н05) was determined.

The laboratory personnel has achieved promising results in the field of human microbiome. GABA-producing Lactobacillus and Bifidobatcerium strains were selected as potential psychobiotics. New concepts and techniques of creating pharmaceuticals for combined therapy and prevention of various diseases were developed.

International collaboration

The laboratory of genetics of microorganisms, Vavilov Institute of General Genetics, RAS is a member of the international consortium TBResist (http://projects.iq.harvard.edu/tbresist/home). The consortium was founded in the year 2011; today, it consists of 29 research groups from 9 countries (USA, South Africa, China, Russia, Sweden etc.). The main focus of the consortium is studying the genetic mechanisms of resistance in M. tuberculosis, in particular MDR and BDR strains. The consortium created a database of whole-genome sequences of 800 M. tuberculosis isolates, accompanied by a detailed characterization of the patients from which the strains were isolated and of the outcome of treatment. An agreement has been signed recently with Rouen University in France to pursue joint research in the field of "Human microbiome – Gut-Brain communication". A project has been prepared for the creation of a joint Russian-French laboratory.

Main publications 2012 - 2017:

1. Lysenkova L., Turchin K., Korolev A., Danilenko V., Bekker O.B., Trenin A.S., Shtil A.A., Preobrazhenskaya M. Synthesis and properties of a novel brominated oligomycin A derivative / Journal of Antibiotics. 2012. P.1-3 http://www.ncbi.nlm.nih.gov/pubmed/22318333

2. Bekker O.B., Mavletova D.A., Liubimova I.K., Mironcheva T.A., Shtil' A.A., Danilenko V.N. Eukaryotic serine-threonine protein kinase inhibitors programmable lysis induction of Streptomyces lividans/ Microbiology (Mikrobiologiya). 2012. V.81 (2), p 160-167.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84859873456&partnerID=40&md5=4660bfdb4a928cd4e08789c412cb2ff4\

3. Prozorov A.A., Zaichikova M.V., Danilenko V.N. Mycobacterium tuberculosis mutants with multidrug resistance: history of origin, genetic and molecular mechanisms of resistance, and emerging challenges/ Russian Journal of Genetics. 2012. 48(1) P. 1-14

http://www.scopus.com/inward/record.url?eid=2-s2.0-84855414702&partnerID=40&md5=50afe7e7550d2138c409987375afe789

4. Zakharevich N.V., Osolodkin D.I., Artamonova I.I., Palyulin V.A., Zefirov N.S., Danilenko V.N. Signatures of the ATP binding pocket as a basis for structural classification of the serine/threonine protein kinases of gram-positive bacteria. Proteins: Structure, Function, and Bioinformatics. 2012. V.80. (5) P.1363 – 1376. http://www.ncbi.nlm.nih.gov/pubmed/22275035

5. Elizarov S.M., Alekseeva M.G., Maslov D.A., Shtil A.A., Danilenko V.N., Chilov G.G., Novikov F.N. Identification of phosphorylation sites in aminoglycoside phosphotransferase VIII from streptomyces rimosus/ Biochemistry (Moscow). 2012. V. 77(11) P. 1258-1265.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84870937932&partnerID=40&md5=3d3a0f6afddfd40fa9f852976a50d6d0

6. Averina O.V., Zakharevich N.V., Danilenko V.N. Identification and Characterization of WhiB-Like Family Proteins of the Bifidobacterium Genus / Anaerobe. 2012. V.18. Р.421-429 http://www.ncbi.nlm.nih.gov/pubmed/22609519

7. Averina O.V., Nezametdinova V.Z., Alekseeva M.G., Danilenko V.N. Genetic instability of probiotic characteristics in the Bifidobacterium longum subsp. longum B379M strain during cultivation and maintenance/ Russian Journal of Genetics. 2012,V 48. P. 1103-1111.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84873728054&partnerID=40&md5=c86aac4571e36dffa14d4bf811ebbc07

8. Lysenkova L., Turchin K., Korolev A., Bykov E., Danilenko V., Bekker O., Trenin A., Elizarov S., Dezhenkova L., Shtil A., Preobrazhenskaya M., A novel acyclic oligomycin А derivative formed via retro-aldol rearrangement of oligomycin A / Journal of Antibiotics. 2012. V.65. P.405–411 http://www.ncbi.nlm.nih.gov/pubmed/22617550

9. Lapa G.B., Bekker O.B., Mirchink E.P., Danilenko V.N., Preobrazhenskaya M.N. Regioselective acylation of congeners of 3-amino-1Hpyrazolo[3,4-b]quinolines, their activity on bacterial serine/threonine protein kinases and in vitro antibacterial (including antimycobacterial) activity / Journal of Enzyme Inhibition and Medicinal Chemistry, 2012; Р.1-6 http://www.ncbi.nlm.nih.gov/pubmed/22957725

10. Prozorov A.A., Zaichikova M.V., Danilenko V.N. Systems of genes and proteins affecting mycobacteria virulence and their homologs participation in conjugation of mycobacterium smegmatis/ Russian Journal of Genetics. 2013. V.49(1) P.110-125.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84873170670&partnerID=40&md5=a82a7dfada1075d3534b5eff146fa947

11. Averina O.V., Alekseeva M.G., Abilev S.K., Il'in V.K., Danilenko V.N. Distribution of genes of toxin-antitoxin systems of mazEF and relBE families in bifidobacteria from human intestinal microbiota / Russian Journal of Genetics. 2013., V. 49(3). P. 275-285.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84875441791&partnerID=40&md5=1b3e1e3ac47618a15dea679335f539da

12. Lyudmila N. Lysenkova, Konstantin F. Turchin , Alexander M. Korolev , Lyubov G. Dezhenkova ,Olga B. Bekker, Alexander A. Shtil, Valery N.Danilenko, Maria N. Preobrazhenskaya. Synthesis and cytotoxicity of oligomycin A derivatives modified in the side chain. Bioorganic Medicinal Chemistry 2013. V 21. Р. 2918-2924 http://www.ncbi.nlm.nih.gov/pubmed/23623676

13. Klimina K.M., Kjasova D.Ch., Poluektova E.U., Leuschner Y., Krügel H., Saluz H.P., Danilenko V.N. Identification and characterization of Toxin-Antitoxin systems in strains of Lactobacillus rhamnosus, isolated from humans.Anaerobe. 2013. Р.1-8 http://www.ncbi.nlm.nih.gov/pubmed/23727113

14. Lysenkova L.N., Turchin K.F., Korolev A.M., Dezhenkova L.G., Preobrazhenskaya M.N., Danilenko V.N., Bekker O.B., Shtil A.A. Study on retroaldol degradation products of antibiotic oligomycin A. Journal of Antibiotics. 2014. V. 67(2) P. 153-158. 1,73 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/24084683

15. Nezametdinova V.Z., Zakharevich N.V., Alekseeva M.G., Averina O.V., Mavletova D.A., Danilenko V.N. Identification and characterization of the serine/threonine protein kinases in Bifidobacterium. Archives of Microbiology. 2014. V.70(3) P.819-34. 1.67 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/24395073

16. Fedorova I.A., Danilenko V.N. Immunogenic properties of a probiotic component of the human gastrointestinal tract microbiota. Biology Bulletin Reviews 2014, Volume 4, Issue 6, p 457-466. 0,71 Impact Factor

https://link.springer.com/article/10.1134/S2079086414060036

17. Prozorov A.A., Fedorova I.A., Bekker O.B., Danilenko V.N. The virulence factors of Mycobacterium tuberculosis: genetic control, new conceptions. Russian Journal of Genetics. 2014. V.50(8)., P.775-797. 0.45 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25731019

18. Bekker O.B., Klimina K. M., Vatlin A.A., Zakharevich N. V., Kasianov A. S., Danilenko V. N. Draft Genome Sequence of Streptomyces fradiae ATCC19609, a strain highly sensitive to antibiotics. Genome Annoncements 2014, V.2, № 6, e01247-14. http://www.ncbi.nlm.nih.gov/pubmed/25477406

19. Zakharevich N.V., Averina O.V., Klimina K.M., Kudryavtseva A.V., Kasianov A.S., Makeev V.J., Danilenko V.N. Complete Genome Sequence of Bifidobacterium longum GT15:Unique Genes for Russian Strains. Genome Announcements. 2014. V.2 (6) e01348-14. IF нет http://www.ncbi.nlm.nih.gov/pubmed/25523785

20. Alekseeva M. G., Mironcheva T. A., Mavletova D. A., Elizarov S. M., Zakharevich N. V., Danilenko V. N. FoF1 -ATP synthase of Streptomyces fradiae ATCC 19609: Structural, biochemical, and functional characterization. Biochemistry (Moscow), 2015, V.80 (3), p 296-309. 1,3 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25761684

21. Bekker O.B., Sokolov D. N., Luzina O. A., Komarova N. I., Gatilov Y. V., Andreevskaya S. N., Smirnova T.G., Maslov D. A., Chernousova L. N., Salakhutdinov N. F., Danilenko V.N. Synthesis and activity of (+)- and (-)-usnic acid derivatives containing 1,3-thiazole cycle against Mycobacterium tuberculosis. Medicinal Chemistry Research. V.24 (7), p 2926-2938. 1.4 Impact Factor

http://www.scopus.com/inward/record.url?eid=2-s2.0-84923844467&partnerID=40&md5=c182a7cf0cb02e9c760c9ece5f18da9e

22. Krügel H., Klimina K., Mrotzek G., Tretyakov A., Schöfl G., Saluz H.-P., Brantl S., Poluektova E., Danilenko V. Expression of the toxin –antitoxin genes yefMLrh, yoeBLrh in human Lactobacillus rhamnosus isolates. J.Basic Microbiology. 2015.V 54 (8). P 982-91. 1,82 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25832734

23. Shur K. V., Klimina K. M., Zakharevich N. V., Maslov D. A., Bekker O. B., Zaychikova M. V., Kamaev E. Y., Kravchenko M. A., Skornyakov S. N., Zhang Y., Danilenko V. N. Draft Genome Sequence of Mycobacterium tuberculosis Strain E186hv of Beijing B0/W Lineage with Reduced Virulence. Genome Announcements 2015, V.3 (3), e00403-15. 0,0 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25953188

24. Yunes RA, Klimina KM, Emelyanov KV, Zakharevich NV, Poluektova EU, Danilenko VN. Draft Genome Sequences of Lactobacillus plantarum Strain 90sk and Lactobacillus brevis Strain 15f: Focusing on Neurotransmitter Genes.Genome Announcements. 2015, V.3(2). e00261-15. 0,0 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25883284

25. Zakharevich N.V., Averina O.V., Klimina K.M., Kudryavtseva A.V., Kasianov A.S., Makeev V. J., Danilenko V.N. Complete Genome Sequence of Bifidobacterium longum GT15: Identification and Characterization of Unique and Global Regulatory Genes. Microbial Ecology, 2015, V.70(3), P.819-34. 3,12 Impact Factor http://www.scopus.com/inward/record.url?eid=2-s2.0-84928128319&partnerID=40&md5=ccff3a73537c842c251136e5d2d85ee8

26. Beliaeva EA, Chervinetz YV, Chervinetz VM, Troshin AV, Mironov AY, Nezametdinova VZ, Averina OV, Danilenko VN. The characteristics of probiotic properties of strains of genus of bifidobacterium separated from gastrointestinal tract of residents of the central region of Russia. Klinichescheskaya Laboratornaya Diagnostika. 2015 Feb;60(2), P. 53-8. 1.124 Impact Factor

http://www.scopus.com/inward/record.url?eid=2-s2.0-84936750109&partnerID=40&md5=1a77f55bb7f73ec305fa092cad41ada9

27. Maslov D.A., Shur K.V., Bekker O.B., Zakharevich N.V., Zaychikova M.V., Klimina K.M., Ustinova V.V, Zhang Y., Chernousova.L.A., Danilenko V.N. Draft genome sequence of a two PZA-resistant isolates of Mycobacterium tuberculosis 13-2459 and 13-4152. Genome Announcements 2015, V3 (4),e00758-15. 0,0 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/26139726

28. Maslov D.A., Zaĭchikova M.V., Chernousova L.N., Bekker O.B. , Smirnova T.G., Larionova E.E., Andreevskaya S.N., Zhang Y., Danilenko V.N. Resistance to pyrazinamide in Russian Mycobacterium tuberculosis isolates: pncA sequencing versus Bactec MGIT 960. Tuberculosis 2015, V.95 p. 608-612. 2,71 Impact Factor http://www.scopus.com/inward/record.url?eid=2-s2.0-84930608992&partnerID=40&md5=df9780d40ffa7c16ab7925afab9d8234

29. Averina O., Alekseeva M., Shkoporov A., Danilenko V.. Functional analysis of the type II toxin-antitoxin systems of the MazEF and RelBE families in Bifidobacterium longum subsp. infantis ATCC 15697. Anaerobe 2015, V.35, Part B, P.59–67. 2,48 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/26210151

30. Dyachkova M.S., Klimina K.M., Kovtun A.S., Zakharevich N.V., Nezametdinova V.Z., Averina O.V., Danilenko V.N. Draft Genome Sequences of Bifidobacterium angulatum GT 102 and Bifidobacterium adolescentis 150: focusing on the genes potentially involved in the gut-brain axis. Genome Announcements, 2015, 3(4), pii: e00709-15. 0,0 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/26139716

31. Luzina O.A.,Sokolov D.N., Pokrovskii M.A., Pokrovskii A.G., Bekker O.B., Danilenko V.N. Synthesis and biological acnivity of usnic acid enamine derivatives. Chemistry of Natural Compounds 2015, V.51(4) P. 646-647. 0.51 Impact Factor

http://www.scopus.com/inward/record.url?eid=2-s2.0-84938989741&partnerID=40&md5=7d1a72bdc97264f1845483c6d1863569

32. Danilenko V.N. Our second brain. Komsomolskaya Pravda No. 105-h (26433-h), the Union Veche 2015, No. 40 p.12. Http://www.souzveche.ru/articles/community/28071/

33. Alekseeva M. G., Mavletova D. A., Kolchina N. V., Nezametdinova V. Z., Danilenko V. N. Isolation and purification of recombinant serine/threonine protein kinases of the strain Bifidobacterium longum B379M and investigation of their activity. Biochemistry (Moscow) 2015; 80(10):1303-1311. 1,3 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/26567574

34. Vatlin A.A., Bekker O.B., Lysenkova L.N., Danilenko V.N. Draft Genome Sequence of Streptomyces fradiae olg1-1, a Strain Resistant to Nitrone-Oligomycin. Genome Announcements. 2015 Oct 22;3(5). pii: e01252-15. 0,0 Impact Factor

http://www.ncbi.nlm.nih.gov/pubmed/26494685

35. Averina O.V., Ermolenko E.I., Ratushniy A.Yu., Tarasova E.A., Borschev Yu.Yu., Leontieva G.F., Kramskaya T.A., Kotyleva M.P., Danilenko V.N., Suvorov A.N. Influence of probiotics on cytokine production in the in vitro and in vivo systems. Medical Immunology (Russia) 10/2015; 17(5):443. 0,48 Impact Factor

http://mimmun.ru/mimmun/article/view/932/821

36. Zaichikova M.V., Zakharevich N.V., Sagaydak M.O., Bogolyubova N.A., Smirnova T.G., Andreevskaya S.A., Chernousova L.N., Alekseeva M.G., Danilenko V.N. Mycobacterium tuberculosis type II toxin-antitoxin systems: a genetic polymorphism, functional properties and the possibility of using for genotyping. journal PLoS One., 2015., e0143682., P.1-15. Impact Factor: 3.23

http://www.ncbi.nlm.nih.gov/pubmed/26658274

37. Lysenkova L.N.; Godovikov I.A.; Korolev A.M.; Danilenko V. N.; Bekker O.B.; Mavletova D.A.; Vatlin, A.A. Synthesis and Anti-Actinomycotic Activity of the Oligomycin A Thiocyanato Derivative Modified at 2-Oxypropyl Side Chain. MACROHETEROCYCLES, 2015; 8(4):424-428. Impact Factor: 0.94 Doi: 10.6060/mhc151084s https://macroheterocycles.isuct.ru/ru/system/files/mhc151084s.pdf

38. Krasnov VP, Vigorov AY, Musiyak VV, Nizova IA, Gruzdev DA, Matveeva TV, Levit GL, Kravchenko MA, Skornyakov SN, Bekker OB, Danilenko VN, Charushin VN.Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides// Bioorg Med Chem Lett. 2016, 26(11), P: 2645-8.

http://www.ncbi.nlm.nih.gov/pubmed/27107949

39. Boyko KM, Gorbacheva MA, Korzhenevskiy DA, Alekseeva MG, Mavletova DA, Zakharevich NV, Elizarov SM, Rudakova NN, Danilenko VN, Popov VO. Structural characterization of the novel aminoglycoside phosphotransferase AphVIII from Streptomyces rimosus with enzymatic activity modulated by phosphorylation// Biochemical and Biophysical Research Communications (BBRC) 2016, 477(4):595-601 doi:10.1016/j.bbrc.2016.06.097 2.371 Impact Factor

http://www.ncbi.nlm.nih.gov/pubmed/27338640

40. Vatlin A.A., Bekker O.B., Danilenko V.N., Lysenkova L.N., Korolev A.M., Shchekotikhin A.E. Sequencing and analysis of the resistome of Streptomyces fradiae ATCC19609 in order to develop a test system for screening of new antimicrobial agents// Russian Journal of Genetics. 2016. V. 52(6) P. 630-635. 0.448 Impact Factor

http://elibrary.ru/item.asp?id=26301574

41. Shur KV, Zaychikova MV, Mikheecheva NE, Klimina.KM, Bekker OB, Zhdanova SN, Ogarkov OB, Danilenko VN. Draft Genome Sequence of Mycobacterium tuberculosis Strain B9741 of Beijing B0/W lineage from HIV positive patient from Siberia // Genom Data. 2016 ;10, P:61-62. eCollection 2016. DOI : 10.1016/j.gdata.2016.08.001 https://www.ncbi.nlm.nih.gov/pubmed/27761405

42. Yunes R.A., Poluektova E.U., Dyachkova M.S., Klimina K.M., Kovtun A.S.,Averina O.V., Orlova V.S., Danilenko V.N. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota// Anaerobes, 2016. - 42:1-8. DOI :10.1016/j.anaerobe.2016.10.011 1.67 Impact Factor

http://www.sciencedirect.com/science/article/pii/S1075996416301305

43. Yunes, RA, Poluektova E.U., Dyachkova MS, Kozlovsky Yu.E., Orlova VS, Danilenko V.N. Selection of gamma-aminobutyric acid producing Lactobacillus and Bifidobacterium symbionts strains as potential psychobiotics // Vestnik of the Peoples' Friendship University of Russia. Series: Ecology and safety. 2016. - No. 4 - P. 67-79.

44. Danilenko V.N. Microbial endocrinology and gut-brain axis - the gastrointestinal tract // ActaNaturae 2016, SPETSVYPUSK, V.1., P.92 1.79 Impact Factor

Https://cloud.mail.ru/public/5Y7h/1fo9GvZRb

45. ​​Klimina KM, Emelyanov KV, Zakharevich NV, Poluektova E.U., Kasyanov AS, Danilenko V.N. The use of type II toxin-antitoxin systems as functional biomarkers for studying strain diversity in human intestinal metagenomas // ActaNaturae 2016, SPETSVYPUSK, V.2., P.112 1.79 Impact Factor https://cloud.mail.ru/public/8hFX/tjPcRas7X

46. Zakharevich NV, Kovtun AS, Averina OV, Nezametdinova VZ, Danilenko VN Genomics of bifidobacteria, unique genes and genes of communication. // ActaNaturae 2016, SPECIALS, V.2., P.201 1.79 Impact Factor https://cloud.mail.ru/public/8hFX/tjPcRas7X

47. Bekker OB, Kravchenko MA, Maslov DA, Danilenko VN. Selection of candidates for potential anti-tuberculosis drugs among compounds of classes of aminopyrimidines and aminopyridines / In the book: Structure and dynamics of molecular systems, a collection of abstracts and reports at the XXIII All-Russian Conference "Structure and dynamics of molecular systems", 14th School of Young Scientists "Spectroscopy of molecular systems" and Symposium "Modern approaches to the treatment of tuberculosis." 2016. P. 14. Http://elibrary.ru/item.asp?id=26797886

48. Maslov DA, Bekker OB, Alekseeva MG, Danilenko VN. Classes of aminopyrimidines and aminopyridines inhibitors of mycobacterial serine-threonine protein kinases as potential new-generation antituberculosis drugs. In the book: Structure and dynamics of molecular systems, a collection of abstracts and reports at the XXIII All-Russian Conference "Structure and Dynamics of Molecular Systems", 14th School of Young Scientists "Spectroscopy Molecular systems "and the symposium" Modern approaches to the treatment of tuberculosis. " 2016. P. 87-88. Http://elibrary.ru/item.asp?id=26798051

49. Shtil A.A., Vatlin A.A., Maslov D.A., Danilenko V.N FOF1 ATP SYNTHASE, A THERAPEUTIC TARGET FOR AIDS ASSOCIATED LYMPHOMA: DESIGN OF NEW INHIBITORS. / HIV infection and immunosuppression, 2016. V. 8(2) P. 112-114. http://elibrary.ru/item.asp?id=26232338

50. Chervinets V.M., Chervinets Yu.V., Belyaeva E.A., Lebedev S.N., Charkova A.R., Troshin A.V., Danilenko V.N., Urdabaev Z.K., Zharasov M.Z., Zevalkina E.V. COMPARATIVE CHARACTERISTICS OF LACTOBACILLI ISOLATED FROM FECES OF HEALTHY PEOPLE LIVING IN THE RUSSIAN FEDERATION AND KAZAKHSTAN // Sovremennye problemy nauki i obrazovanija. – 2016. – № 6. 1.028 Impact Factor https://science-education.ru/ru/article/view?id=25904

51. Lysenkova L.N., Saveljev O.Y., Korolev A.M., Danilenko V.N., Bekker O.B., Mavletova D.A., Vatlin A.A., Omelchuk O.A., Shchekotihin A.E. Synthesis of 33-(R,S)-Bromo-33-deoxyoligomycin A / Macroheterocycles 2016 9(3): 307-313 0.80 Impact Factor https://macroheterocycles.isuct.ru/en/mhc160422s

52. Poluektova E.U., Yunes R.A., Epiphanova M.V., Orlova V.S., Danilenko V.N. The Lactobacillus rhamnosus and Lactobacillus fermentum strains from human biotopes characterized with MLST and toxin-antitoxin gene polymorphism / Archives of microbiology, 2017 Feb 17. 1.760 Impact Factor https://www.ncbi.nlm.nih.gov/pubmed/28213763

53. Averina O. V., Danilenko V. N. Human Intestinal Microbiota: Role in Development and Functioning of the Nervous System / Microbiology, 2017, Vol. 86, No. 1, p. 1–18, 0.796 Impact Factor http://elibrary.ru/item.asp?id=28172244

54. Maslov DA, Bekker OB, Alekseeva MG, Kniazeva LM, Mavletova DA, Afanasyev II, Vasilevich NI, Danilenko VN. AMINOPYRIDINE- AND AMINOPYRIMIDINE-BASED SERINE/THREONINE PROTEIN KINASE INHIBITORS ARE DRUG CANDIDATES FOR TREATING DRUG-RESISTANT TUBERCULOSIS / VESTNIK RGMU, 2017, 1:42-47, 0,106 Impact Factor http://vestnikrgmu.ru/archive/2017/1/4/abstract?lang=ru

55. Shur KV, Maslov DA, Bekker OB, Danilenko VN. MIRU-VNTR GENOTYPING OF MYCOBACTERIUM TUBERCULOSIS CLINICAL ISOLATES FROM MOSCOW REGION / VESTNIK RGMU, 2017, 1:48-51, 0,106 Impact Factor

http://vestnikrgmu.ru/files/issues/2017/1/2017-1-5_ru.pdf?lang=ru

56. Mikheecheva N.E., Zaychikova M.V., Melerzanov A.V., Danilenko V.N. A nonsynonymous SNP catalog of Mycobacterium tuberculosis virulence genes and its use for detecting new potentially virulent sublineages //Genome Biology and Evolution, 2017

4,0 Impact Factor https://doi.org/10.1093/gbe/evx053

57. Lysenkova LN, Saveljev OY, Grammatikova NE, Tsvetkov VB, Bekker OB, Danilenko VN, Dezhenkova LG, Bykov EE, Omelchuk OA, Korolev AM, Shchekotikhin AE Verification of oligomycin A structure: synthesis and biological evaluation of 33-dehydrooligomycin A/J Antibiot (Tokyo). 2017 Apr 19. doi: 10.1038/ja.2017.48. 2.173 Impact Factor https://www.ncbi.nlm.nih.gov/pubmed/28420869

58. Kovtun AS, Alekseeva MG, Averina OV, Danilenko VN. IDENTIFICATION OF AMINOGLYCOSIDE PHOSPHOTRANSFERASES OF CLINICAL BACTERIAL ISOLATES IN THE MICROBIOTA OF RUSSIANS / VESTNIK RGMU, 2017, 2:14-19. 0,106 Impact Factor

http://vestnikrgmu.ru/files/issues/2017/2/2017-2-2_en.pdf?lang=en

59. Zakharevich NV, Danilenko VN. SERINE/THREONINE PROTEIN KINASES OF BACTERIA ARE POTENTIAL TARGETS FOR REGULATION OF HUMAN MICROBIOTA COMPOSITION / VESTNIK RGMU, 2017, 2:20-29. 0,106 Impact Factor

http://vestnikrgmu.ru/files/issues/2017/2/2017-2-3_en.pdf?lang=en

 

 

Laboratory of genetics of microorganisms conducts research in the fields of human microbiome and tuberculosis.

Research topics

-Microbial population genetics of human ecosystems: our studies encompass probiotic commensal bacteria such as lactobacilli and bifidobacteria as well as latent tuberculosis infection;

-Interaction (communication) between the intestinal microbiota and the brain;

-The role of signal transduction systems mediated by serine-threonine protein kinases (STPK) as well as the stress responsive system of toxin-antitoxin (TA) in promoting the adaptation of bacteria to different ecological niches of the human body;

-Identification and characterization of genetic polymorphisms in STPK and TA genes of bacteria isolated from various ethno-regional human populations;

-The search for new genetic mechanisms of interaction between commensal/non-commensal bacteria and the host organism.

-Development of biological targets and test-systems for selecting new potential therapeutic candidate molecules.

Laboratory structure:

1. Group of genetics and comparative genomics of mycobacteria

2.

3. Group of genetics and comparative genomics of lactobacilli

4.

5. Group of genetics and comparative genomics of bifidobacteria

6.

7. Group of microbial endocrinology and the regulatory networks underlying host-microbiota interactions

8.

9. Development of biological targets and test systems

10.

11. Bioinformatics group

12.

Brain – gut – microbiota communication in health and disease.

In the last few years, studying the human microbiome has become a global trend in biomedicine: discovering the bidirectional communication established between gut microbiota and the brain has led to a paradigm shift in understanding the functioning of nervous, endocrine and immune systems. Gut commensal bacteria can synthesize a wide variety of substances involved in neuromodulation including serotonin, dopamine, adrenaline, gamma-aminobutyric acid, short-chain fatty acids etc. In this regard, a new discipline known as microbial endocrinology has emerged.

For the last five years, the laboratory of genetics of microorganisms, Vavilov Institute of General Genetics, Russian Academy of Sciences, has been conducting human microbiome research using different approaches: molecular genetics, genomics and metagenomics. Our ultimate objective is to reveal the mechanisms of interaction between the probiotic bacteria (lactobacilli, bifidobacteria and others) and the host in the absence of stress and under extreme conditions. Our main focus is on direct as well as indirect interaction of bacteria with both the peripheral and central immune systems. One approach is to build gene catalogues containing genes involved in neuromodulation and their orthologues; the next step is to write a program for analyzing sequenced gut metagenomes and revealing signatures (gene compositions and bacterial species to which they belong) in the GIT of healthy people compared to those with depression and cognitive disorders. Sets of instruments for diagnosis and prevention of neurodegenrative disorders are being developed in our laboratory. We are also engaged in the selection of Lactobacillus and Bifidobacterium strains containing gene compositions involved in the synthesis and the production of neuroactive compounds such as gamma-aminobutyric acid, short-chain fatty acids etc. An essential part of our projects is based on creating and maintaining a collection of stool samples and probiotic strains.

Human microbiota biobank

The collection was created in 2009 as a part of two projects:

- Government contract № 02.522.12.2009 from 2008 to 2010, "development of universal starter culture techniques for the application in industrial biotechnology".

- The Russian Foundation for Basic Research № 09-04-13709 from 2009 to 2010, "development of diagnostic test-systems for selecting Bifidobacterium and Lactobacillus strains based on the presence of TA genes promoting adaptation to stress in their genomes".

In the years that followed, the collection was replenished as part of the following projects:

- Government contract, Ministry of Education and Science № 14N08.12.0021 from 2014 to 2015, "Preclinical studies of a probiotic consisting of Bifidobacterium, Lactobacillus and Enterococcus strains, for which genomic sequences are available, for treating nonspecific ulcerative colitis"

- Fundamental research program, Presidium of the Russian Academy of Sciences, from 2014 to 2016, "Fundamental research in the field of biomedical technology", "Development of experimental diagnostic test-systems for species identification and assessment of intra-species diversity of lactobacilli and bifidobacteria in the human intestine using multilocus sequencing". Today, our collection is qualified as a unique Russian collection and is restricted to the use inside our institute. It is considered as basic for creating an interindustrial collection under the aegis of the Federal Agency of Scientific Organizations as part of the consortium "Complex Scientific Research", Human microbiome project.

The human microbiota biobank contains:

-150 human stool samples.

-A collection of Lactobacillus strains belonging to 17 species; the majority of strains belong to 8 species: L. rhamnosus, L. plantarum, L. fermentum, L. casei, L. brevis, L. buchneri, L. helveticus, L. salivarius; 150 strains in total.

-A collection of Bifidobacterium strains belonging to 20 species; 165 strains in total. All bifidobacterial strains were isolated from the gut microbiota of healthy adults and children, living in the central region of Russia.

Lactobacillli and bifidobacteria were screened for the ability gamma-aminobutyric acid (GABA), serotonin, dopamine and other compounds. These properties were found to be species- or strain-specific. Strains with the highest productivity of neuroactive compounds were selected as potential psychobiotics. The genomic sequence of such strains was obtained and deposited in the NCBI database: B. adolescentis 150 (LBHQ00000000); B. angulatum GT 102 (LAHN00000000); L. plantarum 90sk (JXAX00000000); L. brevis 15f (JXCD00000000). Genes involved in production and transport of GABA as well as other neuroactive compounds were identified in the genomes of the sequenced strains.

In case if these collections are lost, they would be impossible to restore. This also applies to the stool samples since the diversity of species and strains and their composition in each sample is unique.

The collection is sustained with the following set of equipment:

-Controlled rate freezer Kryo 360.

-Cryogenic pump LNP4.

-Arpege vessel 170 L.

-Dewar flasks.

-Ultra-low temperature freezer.

-Vacuum freeze dryer.

-Refrigerators and freezers.

-Office appliances.

The biobank is run by a skilled staff that is responsible for freezing the samples and maintaining their long-term viability. Rooms with laminar flow cabinets are available to work with lactobacilli, bifidobacteria and human fecal samples; the rooms apply to safety requirements. Liquid nitrogen is supplied to the biobank every month. A reliable system of power and water supply, as well as ventilation ensure long-term storage of the biological samples.

http://www.microbiome-standards.org/fileadmin/Content/IHMS/_IHMS__Deliverable_Report_D2.2.pdf

The maintenance of the human microbiota biobank is carried out in accordance with certain rules. The following Standard Operation Procedures (SOP) are observed:

1) SOPs and methods of sustaining the viability of samples: monthly subcultivation of samples is used for this purpose.

2)

3) SOPs and quality controlling methods: streaking the samples on agar plates in order to make sure no contamination of the samples have occurred by observing the morphology of the bacterial colonies. PCR of the 16S ribosomal RNA gene is carried out followed by amplicon sequencing for species identification.

4)

5) SOPs and methods of restoring the purity of samples: streaking the samples on agar plates in order to select colonies with typical morphology and other known properties; to confirm the species of the selected colonies, PCR of the 16S ribosomal RNA gene is performed.

6)

7) Methods of replenishing the collection: isolation of microbiota samples (faeces, saliva etc.)

8)

9) Methods of characterizing the samples: species identification by using species specific primers or amplification fo the 16S ribosomal RNA gene with subsequent sequencing of the yielded amplicon. Identification of probiotic properties of strains: production of neuroactive compounds, GABA, antioxidant molecules, neurotransmitters, bacteriocins, immunomodulatory components. Sequencing and metagenomic analysis of potential probiotics. To isolate fecal samples, standardized methods are used: International Human Microbiome Standards:

10)

http://www.microbiome-standards.org/fileadmin/Content/IHMS/_IHMS__Deliverable_Report_D2.2.pdf

Tuberculosis – adequate responses to a new challenge.

For the last ten years, an extensive body of literature dedicated to the mechanisms of occurrence of Multiple Drug Resistance (MDR) and Broad Drug Resistance (BDR) in M. tuberculosis strains as well as to creating new antibiotics and preventive/therapeutic genetically engineered vaccines and their adjuvants against M. tuberculosis strains was published; this emphasizes the complicity of drug resistance in M. tuberculosis, a problem that we has not yet succeeded to solve.

In our laboratory, research aimed at developing new approaches of antibiotic therapy is being carried out; these approaches include the use of mucosal and DNA-vaccines and their adjuvants based on probiotics with immunomodulatory activity. Guidelines for the use of TB drugs, those existing or new, are being developed.

According to WHO’s estimates, approximately 10,4 tuberculosis cases were recorded in 2015 with almost 1,8 million deaths (WHO's Global tuberculosis report, 2016). Although today tuberculosis vaccination is widespread, the incidence remains extremely high due to questioned effectiveness of the BCG vaccine used for global immunization. It varies from 0% to 80% depending on numerous factors, such as age, immune status, etc (Liu J. et al, 2009; Hesseling et al., 2007, Mangtani et al, 2014). Another important problem associated with BCG usage is that it has a high reactogenicity. Besides, BCG can not be used on patients with immunodeficiency and, as shown in recent studies, it lacks effectiveness against pulmonary form of tuberculosis. Therefore, the problem of new TB vaccines development is among the highest priorities in phthisiology. Currently the subunit vaccines are the most promising outlooks (Kaufmann S.H. et al., Int J Infect Dis. 2017, doi: 10.1016/j.ijid.2016.10.018; Méndez-Samperio P., Scand J., Immunol. 2016, 84(4), Pp 204-10). A key challenge in the development of such vaccines is to find the optimal antigenes (Andersen P., Kaufmann S.H., Cold Spring Harb Perspect Med. 2014, 4(6). doi: 10.1101/cshperspect.a018523). The structural elements of M. tuberculosis pathogenicity demonstrate strong antigenicity. M. tuberculosis genome encodes more than 300 of such elements and today they are considered as a basis for the subunit vaccines development (Prozorov et al, 2014; Forrellad et al, 2013). Many of these genes have single nucleotide polymorphisms that accumulated during the evolution. A considerable part of such mutation leads to the amino acid replacement and can affect the structure of protein product and change its properties, including antigenic activity. Today intraspecific diversity of M. tuberculosis is not considered during design of genetically engineered vaccines. Only sequences of the target genes of laboratory strain H37Rv are used. It was found for vaccine M. bovis BCG strain that mutations, arisen during long-term cultivation as a result of microevolution, influence the vaccine’s effectiveness (Brosch R., Proc Natl Acad Sci USA. 2007, 104(13), Pp 5596-601). It is possible that the antigenic activity also varies among different M. tuberculosis strains.

Another promising direction is the development of tuberculosis candidate mucosal vaccine that firstly induces formation of local mucosal immunity. The importance of local anti-TB immunity induction was shown in several studies, in which the intranasal introduction of protective lgA or M. bovis BCG, or pre-treatment of virulent M. tuberculosis with protective lgA led to formation of an effective response to M. tuberculosis (Uranga S. et al., J Vis Exp. 2016, doi: 10.3791/54440; Zimmermann N. et al., EMBO Mol Med. 2016, 8(11), Pp 1325-39; Alvarez N. et al., Malays J Med Sci. 2014, 21(3), Pp 31-7; Alvarez N., BMC Immunol. 2013, Suppl.1-S3). The problems arising from BCG vaccination could be solved by the use of mucosal vaccines, both separate or with the subcutaneous form.

However, today none of the new TB vaccines is used in clinical practice. Often the weakness of such vaccines if the low immunogenicity that implies the use of immunoadjuvants in vaccine’s products. Intranasal probiotic administration also can render adjuvant and immunomodulatory effects, thus increasing the effectiveness of mucosal immune defense. Some probiotic strains, bifidobaceria in particular, can induce production of Th17- and Th1- cytokines (López P. et al., Int J Food Microbiol. 2010, 138(1-2), Pp 157-65), which play crucial role in the mucosal immune response during tuberculosis infection (Uranga S. et al., J Vis Exp. 2016, doi: 10.3791/54440). Hence, intranasal probiotics administration may have an adjuvant effect for the mucosal tuberculosis vaccine and form the protective immunity to virulent strains of M. tuberculosis.

Another serious problem that faces modern phthisiology is the prevalence of strains with multiple and extensive drug resistance. In 2015 there were more than 580 thousands of patients suffering from MDR and XDR tuberculosis. Mutations, affecting structure of a drug target or a drug activator, are crucial for emergence of drug resistance. These strains are so widespread due to the prolonged usage of the same drug set. Bedaquiline has recently became the first in more than 40 years TB drug used in clinics (Chahine E.B., et al., Ann Pharmacother. 2014, 48(1), Pp. 107–115).

In this regard, the development of new TB drugs in of high importance. They must meet certain requirements: a high antimycobacterial activity against both drug-sensitive and MDR M. tuberculosis strains, the presence of a new biotarget and a lack of toxicity.

Nevertheless, in addition to the acquired drug resistance, the intrinsic drug resistance exists that shows low level of antibiotics resistance comparing to the acquired one. When an antibiotic influence M. tuberculosis cell, it activates transcriptional factors that control expression of genes, whose products are able to modify antibiotics or their targets, to reverse transport antibiotics or their active derivatives from M. tuberculosis. In addition, M. tuberculosis cells are capable of constitutive nonspecific reverse transport of antibiotics out of cells due to numerous cellular transporters. The set of genes whose products are involved in the intrinsic drug resistance is defined as resistome.

It is believed that mutations leading to various drugs resistance arise independently, although in some cases the cross-resistance is observed. The cross-resistance arises when the emergence of resistance to one drug leads to the emergence of resistance to other drugs. This phenomenon is triggered by the resistome genes. As described previously, the “cell stress” transcription factors cause the expression of numerous resistome genes, which often results in increased drug resistance of M. tuberculosis cells to several antibiotics classes at once.

The combination of induced, intrinsic, cross-, and drug resistance increases the general level of the pathogen’s drug resistance. Usage of antibiotics in the treatment of concomitant tuberculosis infections or penetration of antibiotics into food can increase M. tuberculosis drug resistance.

The development of high level drug resistance, that combine intrinsic and induced drug resistance and is capable of cross-resistance induction, is one of the most important problems. Its solution will optimize and improve the course of TB treatment. Thus, a complex approach is needed to solve the TB problem. It should include new vaccines development to prevent the disease specifically, and the development of new treatment approaches including the search for new TB drugs.

From 2010 until the present day, the laboratory personnel are conducting research within the framework of contracts with the Ministry of Industry and Trade of Russia, the Ministry of Education and Science of Russia, the RFBR, the RNF, the Russian Academy of Sciences:

Russian Foundation for Basic Research grants

Structural and Functional Characterization of Actinobacterial Serine-Threonine Protein Kinases as Biotargets for Design of Novel Anti-Infective Drugs. (years 2009-2010)

Biotargeted screening of novel anti-infective drugs based on serine-threonine protein kinases of Mycobacterium tuberculosis. (years 2009-2010).

Development of a diagnostic test-system for strains of probiotic bacteria of Bifidobacterium and Lactobacillus genera, carrying toxin-antitoxin systems genes for adaptation to stress conditions. (years 2009-2010).

 

Development of a new test system for screening anti-tuberculosis drugs using Mycobacterium smegmatis as a working model. (years 2011-2012).

 

Study of the functions of aminoglycoside phosphotransferases of Streptomyces rimosus subsp. Rimosus ATCC10970, which accounts for its natural resistance to aminoglycoside antibiotics (years 2017-2019).

Ministry of education and science of Russian Federation

Development of technologies for universal fast-adaptable direct inoculation leavens for biotechnology industry. (years 2008-2010).

Development of new target-specific human and bacterial F0F1 ATP synthases inhibitors. (year 2009-2010)

Preparation of crystals and X-ray diffraction studies of aminoglycoside phosphotransferase type VIII (aphVIII), the key element of test-systems for serine/threonine protein kinases inhibitors screening. (years 2011-2012).

Preclinical studies of a drug based on a complex of bifidobacteria, lactobacilli and enterococci with known genome sequence for treatment of ulcerative colitis. (years 2013-2015).

 

"Preclinical studies of a probiotic consisting of a gluthatione-producing Lactobacillus brevis strain (sequenced genome) for treating drug-induced enteropathy"(years 2016-2018).

 

Preclinical studies of an antituberculous drug based on a synthetic glutamic acid derivative (years 2017-2019)

Ministry of industry and trade of Russian Federation

Preclinical studies of anti-tuberculosis drug, inhibitor of mycobacterial protein kinases. (years 2011-2013).

Preclinical studies of anti-tuberculosis drug, based on semi-synthetic derivatives of usnic acid. (years 2012-2014).

Preclinical studies of a drug based on a selective serine/threonine protein kinase inhibitor for cancer treatment. (years 2013-2015).

Preclinical studies of a drug based on IRAK-4 kinase inhibitor for treatment of autoimmune and chronic inflammatory diseases. (years 2013-2015).

 

Preclinical studies medicament - an inhibitor of glycogen synthase kinase 3 beta, based on N-substituted derivative amrinone for treating type 2 diabetes. (years 2014-2016)РНФ

Complete metagenomic analysis of enteric microbiota in children with autism spectrum disorder: searching for marker gene compositions (years 2017-2019).

Russian Academy of Sciences.

Program of basic research of RAS Presidium “Basic Sciences for Medicine”. Test-system development and inhibitors screening for Streptomyces serine/threonine protein kinase Pk17 – inducers of actinobacterial programmed cell death. (years 2010-2011).

 

Program of basic research of RAS Presidium “Basic research for the development of biomedical technologies”. Development of an experimental sample of diagnostics set for human gut microbiota(years 2014 -2016)

International

RFBR grant NIH (USA-Russia) "Toxins-antitoxins and RpsA in drug resistance and persistence of Mycobacterium tuberculosis" (years 2013-2014).

In the period from 2012 until 2017, the results of research were reported at the following events:

International Human Microbiome Congress, Paris, France, March 19-21, 2012 .

US-RU Workshop “TB in AIDS-Infected Individuals: New Paradigm, Diagnosis and Drug Development” Within US-RU Scientific Forum for Biomedical Research, Central Research Institute of Epidemiology, Moscow, June 28-29, 2012.

US-RU joint workshop “Human Microbiome: Metagenomics, New Biomarkers of Disease, Translational Research in Personalized Medicine” within US-RU Scientific Forum for Biomedical Research Vavilov Institute of General Genetics, Moscow, September 17-18, 2012.

Conference "Postgenomic methods of analysis in biology, laboratory and clinical medicine", Kazan (Privolzhsky) Federal University, Kazan, November 22 - 24, 2012.

Second International Scientific Conference “REGENERATIVE MEDICINE & HEALTHY AGING”, Astana, Kazakhstan, November 1-2, 2012.

International Conference “High-Throughpup Sequencing in Genomics” HSG, Russia, Novosibirsk, 21.07.2013.

«The 5th Congress of European Microbiologists»,Germany, Leipzig, 21.07.2013.

«38th FEBS Congress» Russia, St. Petersburg, 06.07.2013.

"19 Russian-American Symposium on Biotechnology in Industry, Agriculture and Healthcare", USA, Philadelphia, 11.03.2014.

Ural Scientific Forum "Contemporary Problems of Organic Chemistry", Russia, Ekaterinburg, 08.06.2014

International Conference “High-Throughpup Sequencing in Genomics”, Russia, Novosibirsk, 21.07.2013

 

The 5th Congress of European Microbiologists, Germany, Leipzig 21.07.2013

 

38th FEBS Congress, Saint Petersburg, Russia, July 6-11, 2013

International conference dedicated to the 75th anniversary of the Department of Biotechnology and the 20th anniversary of the Institute of Biology and Biotechnology "Contemporary issues of Biotechnology, Nanotechnology and Physico-Chemical Biology" Kazakhstan, Almaty, 11/21/2013

19 Russian-American Symposium on Biotechnology in industry, agriculture and health, Philadelphia, USA , March 11 - 16, 2014

 

Ecoforum, Saint Petersburg, Russia, September 21-24, 2014

 

International Forum "Pharmaceuticals and Medical Products" 2014, Tomsk, Russia, September 23-24, 2014

8th International Biotechnological Forum-Exhibition "RosBioTech 2014" Moscow, Russia, October 27-28, 2014

The 2015 TB SUMMIT European Scientific Conferences, United Kingdom, London, March 23-26, 2015

5th International Human Microbiome Congress - IHMC Congress (IHMC), Luxembourg, 31March – 2 April, 2015

International Military Technical Forum "ARMY-2015" round table "Medical support of the Armed Forces of the Russian Federation in the Arctic", June 16-19, CEC "Patriot", Moscow region, Kubinka

International Scientific Conference on Probiotics and Prebiotics – IPC2015, Budapest, 23rd – 25th June 2015

 

MedChem 2015, 2nd Russian Conference on Medicinal Chemistry, Novosibirsk, Russia, July 5-10, 2015

 

Microbios 2015, Tashkent, Uzbekistan, November 25-27, 2015

Workshop "Scientific cooperation of the Russian Foundation for Fundamental Research and National Institutes of Health of the USA, St. Petersburg, Russia, 04/13/2016

III International Scientific Conference "Genetics and biotechnology of the XXI century: problems, achievements, prospects", dedicated to the 115th anniversary of the birth of Academician A.R. Zhebrak and XI Congress of the Belarusian Society of Geneticists and Breeders, Minsk, 23-25 November 2016

International Congress: Biotechnology: State and Prospects for Development, Moscow, Gostiny Dvor, February 20-22, 2017

Second UK-Russia roundtable discussion “Antimicrobial resistance (AMR): action plans implementation”, Москва, 20-21 февраля 2017

Round table "Microbiota (microbiota) of man in norm and pathology" X International scientific conference "Microbial biotechnologies: fundamental and applied aspects" Minsk, June 7, 2017.

Laboratory achievements

Over the last years, we created a unique technology panel for screening drugs to treat socially significant diseases such as tuberculosis. Hundreds new substances belonging to different classes of drugs were screened (benzodiazepines, benzophtalazines, carboranes, Cyclopentenediones, indolylmaleimides, pyridazines, pyrazoles, quinoxalines, thiazoles, thiazole tetrazines) which allowed selecting candidate molecules for treating infectious diseases including M. tuberculosis as well as other immunological and oncological diseases. As STPK represent a target for many molecular species that are potential drugs, the laboratory personnel set up an efficacious testing panel to screen for serine-threonine protein kinase inhibitors. A collection of probiotic Lactobacillus and Bifidobacterium strains was created and characterized to be used for developing pharmaceuticals with immunomodulatory, antioxidant and anti-inflammatory properties as well as adjuvants and vaccines of different classes.

For the first time, type II toxin-antitoxin systems of lactobacilli and bifidobacteria were identified and characterized yielding enough knowledge to develop diagnosticums for strain identification in human gut metagenomes. The immunomodulatory activity exhibited by Lactobacillus and Bifidobacterium strains was shown to be strain-specific. The genomes of 20 Lactobacillus strains, 10 Bifidobacterium strains, 5 Streptomyces strains and 20 Tuberculosis strains were sequenced and annotated. A genotyping method based on polymorphisms in type II toxin-antitoxin and virulence genes of M. tuberculosis was developed. 3D crystal structure of the aminoglycoside transferase aph VIII (deposited in PDB under the number 4Н05) was determined.

The laboratory personnel has achieved promising results in the field of human microbiome. GABA-producing Lactobacillus and Bifidobatcerium strains were selected as potential psychobiotics. New concepts and techniques of creating pharmaceuticals for combined therapy and prevention of various diseases were developed.

International collaboration

The laboratory of genetics of microorganisms, Vavilov Institute of General Genetics, RAS is a member of the international consortium TBResist (http://projects.iq.harvard.edu/tbresist/home). The consortium was founded in the year 2011; today, it consists of 29 research groups from 9 countries (USA, South Africa, China, Russia, Sweden etc.). The main focus of the consortium is studying the genetic mechanisms of resistance in M. tuberculosis, in particular MDR and BDR strains. The consortium created a database of whole-genome sequences of 800 M. tuberculosis isolates, accompanied by a detailed characterization of the patients from which the strains were isolated and of the outcome of treatment. An agreement has been signed recently with Rouen University in France to pursue joint research in the field of "Human microbiome – Gut-Brain communication". A project has been prepared for the creation of a joint Russian-French laboratory.

Main publications 2012 - 2017:

1. Lysenkova L., Turchin K., Korolev A., Danilenko V., Bekker O.B., Trenin A.S., Shtil A.A., Preobrazhenskaya M. Synthesis and properties of a novel brominated oligomycin A derivative / Journal of Antibiotics. 2012. P.1-3 http://www.ncbi.nlm.nih.gov/pubmed/22318333

2.

3. Bekker O.B., Mavletova D.A., Liubimova I.K., Mironcheva T.A., Shtil' A.A., Danilenko V.N. Eukaryotic serine-threonine protein kinase inhibitors programmable lysis induction of Streptomyces lividans/ Microbiology (Mikrobiologiya). 2012. V.81 (2), p 160-167.

4.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84859873456&partnerID=40&md5=4660bfdb4a928cd4e08789c412cb2ff4\

5. Prozorov A.A., Zaichikova M.V., Danilenko V.N. Mycobacterium tuberculosis mutants with multidrug resistance: history of origin, genetic and molecular mechanisms of resistance, and emerging challenges/ Russian Journal of Genetics. 2012. 48(1) P. 1-14

6.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84855414702&partnerID=40&md5=50afe7e7550d2138c409987375afe789

7. Zakharevich N.V., Osolodkin D.I., Artamonova I.I., Palyulin V.A., Zefirov N.S., Danilenko V.N. Signatures of the ATP binding pocket as a basis for structural classification of the serine/threonine protein kinases of gram-positive bacteria. Proteins: Structure, Function, and Bioinformatics. 2012. V.80. (5) P.1363 – 1376. http://www.ncbi.nlm.nih.gov/pubmed/22275035

8.

9. Elizarov S.M., Alekseeva M.G., Maslov D.A., Shtil A.A., Danilenko V.N., Chilov G.G., Novikov F.N. Identification of phosphorylation sites in aminoglycoside phosphotransferase VIII from streptomyces rimosus/ Biochemistry (Moscow). 2012. V. 77(11) P. 1258-1265.

10.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84870937932&partnerID=40&md5=3d3a0f6afddfd40fa9f852976a50d6d0

11. Averina O.V., Zakharevich N.V., Danilenko V.N. Identification and Characterization of WhiB-Like Family Proteins of the Bifidobacterium Genus / Anaerobe. 2012. V.18. Р.421-429 http://www.ncbi.nlm.nih.gov/pubmed/22609519

12.

13. Averina O.V., Nezametdinova V.Z., Alekseeva M.G., Danilenko V.N. Genetic instability of probiotic characteristics in the Bifidobacterium longum subsp. longum B379M strain during cultivation and maintenance/ Russian Journal of Genetics. 2012,V 48. P. 1103-1111.

14.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84873728054&partnerID=40&md5=c86aac4571e36dffa14d4bf811ebbc07

15. Lysenkova L., Turchin K., Korolev A., Bykov E., Danilenko V., Bekker O., Trenin A., Elizarov S., Dezhenkova L., Shtil A., Preobrazhenskaya M., A novel acyclic oligomycin А derivative formed via retro-aldol rearrangement of oligomycin A / Journal of Antibiotics. 2012. V.65. P.405–411 http://www.ncbi.nlm.nih.gov/pubmed/22617550

16.

17. Lapa G.B., Bekker O.B., Mirchink E.P., Danilenko V.N., Preobrazhenskaya M.N. Regioselective acylation of congeners of 3-amino-1Hpyrazolo[3,4-b]quinolines, their activity on bacterial serine/threonine protein kinases and in vitro antibacterial (including antimycobacterial) activity / Journal of Enzyme Inhibition and Medicinal Chemistry, 2012; Р.1-6 http://www.ncbi.nlm.nih.gov/pubmed/22957725

18.

19. Prozorov A.A., Zaichikova M.V., Danilenko V.N. Systems of genes and proteins affecting mycobacteria virulence and their homologs participation in conjugation of mycobacterium smegmatis/ Russian Journal of Genetics. 2013. V.49(1) P.110-125.

20.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84873170670&partnerID=40&md5=a82a7dfada1075d3534b5eff146fa947

21. Averina O.V., Alekseeva M.G., Abilev S.K., Il'in V.K., Danilenko V.N. Distribution of genes of toxin-antitoxin systems of mazEF and relBE families in bifidobacteria from human intestinal microbiota / Russian Journal of Genetics. 2013., V. 49(3). P. 275-285.

22.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84875441791&partnerID=40&md5=1b3e1e3ac47618a15dea679335f539da

23. Lyudmila N. Lysenkova, Konstantin F. Turchin , Alexander M. Korolev , Lyubov G. Dezhenkova ,Olga B. Bekker, Alexander A. Shtil, Valery N.Danilenko, Maria N. Preobrazhenskaya. Synthesis and cytotoxicity of oligomycin A derivatives modified in the side chain. Bioorganic Medicinal Chemistry 2013. V 21. Р. 2918-2924 http://www.ncbi.nlm.nih.gov/pubmed/23623676

24.

25. Klimina K.M., Kjasova D.Ch., Poluektova E.U., Leuschner Y., Krügel H., Saluz H.P., Danilenko V.N. Identification and characterization of Toxin-Antitoxin systems in strains of Lactobacillus rhamnosus, isolated from humans.Anaerobe. 2013. Р.1-8 http://www.ncbi.nlm.nih.gov/pubmed/23727113

26.

27. Lysenkova L.N., Turchin K.F., Korolev A.M., Dezhenkova L.G., Preobrazhenskaya M.N., Danilenko V.N., Bekker O.B., Shtil A.A. Study on retroaldol degradation products of antibiotic oligomycin A. Journal of Antibiotics. 2014. V. 67(2) P. 153-158. 1,73 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/24084683

28.

29. Nezametdinova V.Z., Zakharevich N.V., Alekseeva M.G., Averina O.V., Mavletova D.A., Danilenko V.N. Identification and characterization of the serine/threonine protein kinases in Bifidobacterium. Archives of Microbiology. 2014. V.70(3) P.819-34. 1.67 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/24395073

30.

31. Fedorova I.A., Danilenko V.N. Immunogenic properties of a probiotic component of the human gastrointestinal tract microbiota. Biology Bulletin Reviews 2014, Volume 4, Issue 6, p 457-466. 0,71 Impact Factor

32.

https://link.springer.com/article/10.1134/S2079086414060036

33. Prozorov A.A., Fedorova I.A., Bekker O.B., Danilenko V.N. The virulence factors of Mycobacterium tuberculosis: genetic control, new conceptions. Russian Journal of Genetics. 2014. V.50(8)., P.775-797. 0.45 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25731019

34.

35. Bekker O.B., Klimina K. M., Vatlin A.A., Zakharevich N. V., Kasianov A. S., Danilenko V. N. Draft Genome Sequence of Streptomyces fradiae ATCC19609, a strain highly sensitive to antibiotics. Genome Annoncements 2014, V.2, № 6, e01247-14. http://www.ncbi.nlm.nih.gov/pubmed/25477406

36.

37. Zakharevich N.V., Averina O.V., Klimina K.M., Kudryavtseva A.V., Kasianov A.S., Makeev V.J., Danilenko V.N. Complete Genome Sequence of Bifidobacterium longum GT15:Unique Genes for Russian Strains. Genome Announcements. 2014. V.2 (6) e01348-14. IF нет http://www.ncbi.nlm.nih.gov/pubmed/25523785

38.

39. Alekseeva M. G., Mironcheva T. A., Mavletova D. A., Elizarov S. M., Zakharevich N. V., Danilenko V. N. FoF1 -ATP synthase of Streptomyces fradiae ATCC 19609: Structural, biochemical, and functional characterization. Biochemistry (Moscow), 2015, V.80 (3), p 296-309. 1,3 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25761684

40.

41. Bekker O.B., Sokolov D. N., Luzina O. A., Komarova N. I., Gatilov Y. V., Andreevskaya S. N., Smirnova T.G., Maslov D. A., Chernousova L. N., Salakhutdinov N. F., Danilenko V.N. Synthesis and activity of (+)- and (-)-usnic acid derivatives containing 1,3-thiazole cycle against Mycobacterium tuberculosis. Medicinal Chemistry Research. V.24 (7), p 2926-2938. 1.4 Impact Factor

42.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84923844467&partnerID=40&md5=c182a7cf0cb02e9c760c9ece5f18da9e

43. Krügel H., Klimina K., Mrotzek G., Tretyakov A., Schöfl G., Saluz H.-P., Brantl S., Poluektova E., Danilenko V. Expression of the toxin –antitoxin genes yefMLrh, yoeBLrh in human Lactobacillus rhamnosus isolates. J.Basic Microbiology. 2015.V 54 (8). P 982-91. 1,82 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25832734

44.

45. Shur K. V., Klimina K. M., Zakharevich N. V., Maslov D. A., Bekker O. B., Zaychikova M. V., Kamaev E. Y., Kravchenko M. A., Skornyakov S. N., Zhang Y., Danilenko V. N. Draft Genome Sequence of Mycobacterium tuberculosis Strain E186hv of Beijing B0/W Lineage with Reduced Virulence. Genome Announcements 2015, V.3 (3), e00403-15. 0,0 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25953188

46.

47. Yunes RA, Klimina KM, Emelyanov KV, Zakharevich NV, Poluektova EU, Danilenko VN. Draft Genome Sequences of Lactobacillus plantarum Strain 90sk and Lactobacillus brevis Strain 15f: Focusing on Neurotransmitter Genes.Genome Announcements. 2015, V.3(2). e00261-15. 0,0 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/25883284

48.

49. Zakharevich N.V., Averina O.V., Klimina K.M., Kudryavtseva A.V., Kasianov A.S., Makeev V. J., Danilenko V.N. Complete Genome Sequence of Bifidobacterium longum GT15: Identification and Characterization of Unique and Global Regulatory Genes. Microbial Ecology, 2015, V.70(3), P.819-34. 3,12 Impact Factor http://www.scopus.com/inward/record.url?eid=2-s2.0-84928128319&partnerID=40&md5=ccff3a73537c842c251136e5d2d85ee8

50.

51. Beliaeva EA, Chervinetz YV, Chervinetz VM, Troshin AV, Mironov AY, Nezametdinova VZ, Averina OV, Danilenko VN. The characteristics of probiotic properties of strains of genus of bifidobacterium separated from gastrointestinal tract of residents of the central region of Russia. Klinichescheskaya Laboratornaya Diagnostika. 2015 Feb;60(2), P. 53-8. 1.124 Impact Factor

52.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84936750109&partnerID=40&md5=1a77f55bb7f73ec305fa092cad41ada9

53. Maslov D.A., Shur K.V., Bekker O.B., Zakharevich N.V., Zaychikova M.V., Klimina K.M., Ustinova V.V, Zhang Y., Chernousova.L.A., Danilenko V.N. Draft genome sequence of a two PZA-resistant isolates of Mycobacterium tuberculosis 13-2459 and 13-4152. Genome Announcements 2015, V3 (4),e00758-15. 0,0 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/26139726

54.

55. Maslov D.A., Zaĭchikova M.V., Chernousova L.N., Bekker O.B. , Smirnova T.G., Larionova E.E., Andreevskaya S.N., Zhang Y., Danilenko V.N. Resistance to pyrazinamide in Russian Mycobacterium tuberculosis isolates: pncA sequencing versus Bactec MGIT 960. Tuberculosis 2015, V.95 p. 608-612. 2,71 Impact Factor http://www.scopus.com/inward/record.url?eid=2-s2.0-84930608992&partnerID=40&md5=df9780d40ffa7c16ab7925afab9d8234

56.

57. Averina O., Alekseeva M., Shkoporov A., Danilenko V.. Functional analysis of the type II toxin-antitoxin systems of the MazEF and RelBE families in Bifidobacterium longum subsp. infantis ATCC 15697. Anaerobe 2015, V.35, Part B, P.59–67. 2,48 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/26210151

58.

59. Dyachkova M.S., Klimina K.M., Kovtun A.S., Zakharevich N.V., Nezametdinova V.Z., Averina O.V., Danilenko V.N. Draft Genome Sequences of Bifidobacterium angulatum GT 102 and Bifidobacterium adolescentis 150: focusing on the genes potentially involved in the gut-brain axis. Genome Announcements, 2015, 3(4), pii: e00709-15. 0,0 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/26139716

60.

61. Luzina O.A.,Sokolov D.N., Pokrovskii M.A., Pokrovskii A.G., Bekker O.B., Danilenko V.N. Synthesis and biological acnivity of usnic acid enamine derivatives. Chemistry of Natural Compounds 2015, V.51(4) P. 646-647. 0.51 Impact Factor

62.

http://www.scopus.com/inward/record.url?eid=2-s2.0-84938989741&partnerID=40&md5=7d1a72bdc97264f1845483c6d1863569

63. Danilenko V.N. Our second brain. Komsomolskaya Pravda No. 105-h (26433-h), the Union Veche 2015, No. 40 p.12. Http://www.souzveche.ru/articles/community/28071/

64.

65. Alekseeva M. G., Mavletova D. A., Kolchina N. V., Nezametdinova V. Z., Danilenko V. N. Isolation and purification of recombinant serine/threonine protein kinases of the strain Bifidobacterium longum B379M and investigation of their activity. Biochemistry (Moscow) 2015; 80(10):1303-1311. 1,3 Impact Factor http://www.ncbi.nlm.nih.gov/pubmed/26567574

66.

67. Vatlin A.A., Bekker O.B., Lysenkova L.N., Danilenko V.N. Draft Genome Sequence of Streptomyces fradiae olg1-1, a Strain Resistant to Nitrone-Oligomycin. Genome Announcements. 2015 Oct 22;3(5). pii: e01252-15. 0,0 Impact Factor

68.

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69. Averina O.V., Ermolenko E.I., Ratushniy A.Yu., Tarasova E.A., Borschev Yu.Yu., Leontieva G.F., Kramskaya T.A., Kotyleva M.P., Danilenko V.N., Suvorov A.N. Influence of probiotics on cytokine production in the in vitro and in vivo systems. Medical Immunology (Russia) 10/2015; 17(5):443. 0,48 Impact Factor

70.

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71. Zaichikova M.V., Zakharevich N.V., Sagaydak M.O., Bogolyubova N.A., Smirnova T.G., Andreevskaya S.A., Chernousova L.N., Alekseeva M.G., Danilenko V.N. Mycobacterium tuberculosis type II toxin-antitoxin systems: a genetic polymorphism, functional properties and the possibility of using for genotyping. journal PLoS One., 2015., e0143682., P.1-15. Impact Factor: 3.23

72.

http://www.ncbi.nlm.nih.gov/pubmed/26658274

73. Lysenkova L.N.; Godovikov I.A.; Korolev A.M.; Danilenko V. N.; Bekker O.B.; Mavletova D.A.; Vatlin, A.A. Synthesis and Anti-Actinomycotic Activity of the Oligomycin A Thiocyanato Derivative Modified at 2-Oxypropyl Side Chain. MACROHETEROCYCLES, 2015; 8(4):424-428. Impact Factor: 0.94 Doi: 10.6060/mhc151084s https://macroheterocycles.isuct.ru/ru/system/files/mhc151084s.pdf

74.

75. Krasnov VP, Vigorov AY, Musiyak VV, Nizova IA, Gruzdev DA, Matveeva TV, Levit GL, Kravchenko MA, Skornyakov SN, Bekker OB, Danilenko VN, Charushin VN.Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides// Bioorg Med Chem Lett. 2016, 26(11), P: 2645-8.

76.

http://www.ncbi.nlm.nih.gov/pubmed/27107949

77. Boyko KM, Gorbacheva MA, Korzhenevskiy DA, Alekseeva MG, Mavletova DA, Zakharevich NV, Elizarov SM, Rudakova NN, Danilenko VN, Popov VO. Structural characterization of the novel aminoglycoside phosphotransferase AphVIII from Streptomyces rimosus with enzymatic activity modulated by phosphorylation// Biochemical and Biophysical Research Communications (BBRC) 2016, 477(4):595-601 doi:10.1016/j.bbrc.2016.06.097 2.371 Impact Factor

78.

http://www.ncbi.nlm.nih.gov/pubmed/27338640

79. Vatlin A.A., Bekker O.B., Danilenko V.N., Lysenkova L.N., Korolev A.M., Shchekotikhin A.E. Sequencing and analysis of the resistome of Streptomyces fradiae ATCC19609 in order to develop a test system for screening of new antimicrobial agents// Russian Journal of Genetics. 2016. V. 52(6) P. 630-635. 0.448 Impact Factor

80.

http://elibrary.ru/item.asp?id=26301574

81. Shur KV, Zaychikova MV, Mikheecheva NE, Klimina.KM, Bekker OB, Zhdanova SN, Ogarkov OB, Danilenko VN. Draft Genome Sequence of Mycobacterium tuberculosis Strain B9741 of Beijing B0/W lineage from HIV positive patient from Siberia // Genom Data. 2016 ;10, P:61-62. eCollection 2016. DOI : 10.1016/j.gdata.2016.08.001 https://www.ncbi.nlm.nih.gov/pubmed/27761405

82.

83. Yunes R.A., Poluektova E.U., Dyachkova M.S., Klimina K.M., Kovtun A.S.,Averina O.V., Orlova V.S., Danilenko V.N. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota// Anaerobes, 2016. - 42:1-8. DOI :10.1016/j.anaerobe.2016.10.011 1.67 Impact Factor

84.

http://www.sciencedirect.com/science/article/pii/S1075996416301305

85. Yunes, RA, Poluektova E.U., Dyachkova MS, Kozlovsky Yu.E., Orlova VS, Danilenko V.N. Selection of gamma-aminobutyric acid producing Lactobacillus and Bifidobacterium symbionts strains as potential psychobiotics // Vestnik of the Peoples' Friendship University of Russia. Series: Ecology and safety. 2016. - No. 4 - P. 67-79.

86.

87. Danilenko V.N. Microbial endocrinology and gut-brain axis - the gastrointestinal tract // ActaNaturae 2016, SPETSVYPUSK, V.1., P.92 1.79 Impact Factor

88.

Https://cloud.mail.ru/public/5Y7h/1fo9GvZRb

89. ​​Klimina KM, Emelyanov KV, Zakharevich NV, Poluektova E.U., Kasyanov AS, Danilenko V.N. The use of type II toxin-antitoxin systems as functional biomarkers for studying strain diversity in human intestinal metagenomas // ActaNaturae 2016, SPETSVYPUSK, V.2., P.112 1.79 Impact Factor https://cloud.mail.ru/public/8hFX/tjPcRas7X

90.

91. Zakharevich NV, Kovtun AS, Averina OV, Nezametdinova VZ, Danilenko VN Genomics of bifidobacteria, unique genes and genes of communication. // ActaNaturae 2016, SPECIALS, V.2., P.201 1.79 Impact Factor https://cloud.mail.ru/public/8hFX/tjPcRas7X

92.

93. Bekker OB, Kravchenko MA, Maslov DA, Danilenko VN. Selection of candidates for potential anti-tuberculosis drugs among compounds of classes of aminopyrimidines and aminopyridines / In the book: Structure and dynamics of molecular systems, a collection of abstracts and reports at the XXIII All-Russian Conference "Structure and dynamics of molecular systems", 14th School of Young Scientists "Spectroscopy of molecular systems" and Symposium "Modern approaches to the treatment of tuberculosis." 2016. P. 14. Http://elibrary.ru/item.asp?id=26797886

94.

95. Maslov DA, Bekker OB, Alekseeva MG, Danilenko VN. Classes of aminopyrimidines and aminopyridines inhibitors of mycobacterial serine-threonine protein kinases as potential new-generation antituberculosis drugs. In the book: Structure and dynamics of molecular systems, a collection of abstracts and reports at the XXIII All-Russian Conference "Structure and Dynamics of Molecular Systems", 14th School of Young Scientists "Spectroscopy Molecular systems "and the symposium" Modern approaches to the treatment of tuberculosis. " 2016. P. 87-88. Http://elibrary.ru/item.asp?id=26798051

96.

97. Shtil A.A., Vatlin A.A., Maslov D.A., Danilenko V.N FOF1 ATP SYNTHASE, A THERAPEUTIC TARGET FOR AIDS ASSOCIATED LYMPHOMA: DESIGN OF NEW INHIBITORS. / HIV infection and immunosuppression, 2016. V. 8(2) P. 112-114. http://elibrary.ru/item.asp?id=26232338

98.

99. Chervinets V.M., Chervinets Yu.V., Belyaeva E.A., Lebedev S.N., Charkova A.R., Troshin A.V., Danilenko V.N., Urdabaev Z.K., Zharasov M.Z., Zevalkina E.V. COMPARATIVE CHARACTERISTICS OF LACTOBACILLI ISOLATED FROM FECES OF HEALTHY PEOPLE LIVING IN THE RUSSIAN FEDERATION AND KAZAKHSTAN // Sovremennye problemy nauki i obrazovanija. – 2016. – № 6. 1.028 Impact Factor https://science-education.ru/ru/article/view?id=25904

100.

101. Lysenkova L.N., Saveljev O.Y., Korolev A.M., Danilenko V.N., Bekker O.B., Mavletova D.A., Vatlin A.A., Omelchuk O.A., Shchekotihin A.E. Synthesis of 33-(R,S)-Bromo-33-deoxyoligomycin A / Macroheterocycles 2016 9(3): 307-313 0.80 Impact Factor https://macroheterocycles.isuct.ru/en/mhc160422s

102.

103. Poluektova E.U., Yunes R.A., Epiphanova M.V., Orlova V.S., Danilenko V.N. The Lactobacillus rhamnosus and Lactobacillus fermentum strains from human biotopes characterized with MLST and toxin-antitoxin gene polymorphism / Archives of microbiology, 2017 Feb 17. 1.760 Impact Factor https://www.ncbi.nlm.nih.gov/pubmed/28213763

104.

105. Averina O. V., Danilenko V. N. Human Intestinal Microbiota: Role in Development and Functioning of the Nervous System / Microbiology, 2017, Vol. 86, No. 1, p. 1–18, 0.796 Impact Factor http://elibrary.ru/item.asp?id=28172244

106.

107. Maslov DA, Bekker OB, Alekseeva MG, Kniazeva LM, Mavletova DA, Afanasyev II, Vasilevich NI, Danilenko VN. AMINOPYRIDINE- AND AMINOPYRIMIDINE-BASED SERINE/THREONINE PROTEIN KINASE INHIBITORS ARE DRUG CANDIDATES FOR TREATING DRUG-RESISTANT TUBERCULOSIS / VESTNIK RGMU, 2017, 1:42-47, 0,106 Impact Factor http://vestnikrgmu.ru/archive/2017/1/4/abstract?lang=ru

108.

109. Shur KV, Maslov DA, Bekker OB, Danilenko VN. MIRU-VNTR GENOTYPING OF MYCOBACTERIUM TUBERCULOSIS CLINICAL ISOLATES FROM MOSCOW REGION / VESTNIK RGMU, 2017, 1:48-51, 0,106 Impact Factor

110.

http://vestnikrgmu.ru/files/issues/2017/1/2017-1-5_ru.pdf?lang=ru

111. Mikheecheva N.E., Zaychikova M.V., Melerzanov A.V., Danilenko V.N. A nonsynonymous SNP catalog of Mycobacterium tuberculosis virulence genes and its use for detecting new potentially virulent sublineages //Genome Biology and Evolution, 2017

112.

4,0 Impact Factor https://doi.org/10.1093/gbe/evx053

113. Lysenkova LN, Saveljev OY, Grammatikova NE, Tsvetkov VB, Bekker OB, Danilenko VN, Dezhenkova LG, Bykov EE, Omelchuk OA, Korolev AM, Shchekotikhin AE Verification of oligomycin A structure: synthesis and biological evaluation of 33-dehydrooligomycin A/J Antibiot (Tokyo). 2017 Apr 19. doi: 10.1038/ja.2017.48. 2.173 Impact Factor https://www.ncbi.nlm.nih.gov/pubmed/28420869

114.

115. Kovtun AS, Alekseeva MG, Averina OV, Danilenko VN. IDENTIFICATION OF AMINOGLYCOSIDE PHOSPHOTRANSFERASES OF CLINICAL BACTERIAL ISOLATES IN THE MICROBIOTA OF RUSSIANS / VESTNIK RGMU, 2017, 2:14-19. 0,106 Impact Factor

116.

http://vestnikrgmu.ru/files/issues/2017/2/2017-2-2_en.pdf?lang=en

117. Zakharevich NV, Danilenko VN. SERINE/THREONINE PROTEIN KINASES OF BACTERIA ARE POTENTIAL TARGETS FOR REGULATION OF HUMAN MICROBIOTA COMPOSITION / VESTNIK RGMU, 2017, 2:20-29. 0,106 Impact Factor

118.

http://vestnikrgmu.ru/files/issues/2017/2/2017-2-3_en.pdf?lang=en