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

CV

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: the discovery of the bidirectional communication between the 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 bacterial genetics at the 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 gut of healthy people compared to those with depression and cognitive disorders. Sets of instruments for diagnosis and prevention of neurodegenerative 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 (2008 – 2010), "Development of universal starter culture techniques for the application in industrial biotechnology".

- The Russian Foundation for Basic Research № 09-04-13709 (2009 – 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:

- Ministry of Education and Science government contract, № 14N08.12.0021 (2014 – 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 of the Presidium of the Russian Academy of Sciences "Fundamental research in the field of biomedical technology" (2014 – 2016),  "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 one in Russia 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 to produce 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 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 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.

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 has 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. 4) Methods of replenishing the collection: isolation of microbiota samples (faeces, saliva etc.) 5) Methods of characterizing the samples: species identification by using species-specific primers or amplification of the 16S ribosomal RNA gene with subsequent sequencing of the yielded amplicon. Identification the strains’ probiotic properties: production of neuroactive compounds, GABA, antioxidant molecules, neurotransmitters, bacteriocins, immunomodulatory components. Sequencing and metagenomic analysis of potential probiotics. Standardized methods are used for the fecal samples’ isolation: International Human Microbiome Standards

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

Tuberculosis – adequate responses to new challenges

In the last ten years, an extensive body of literature dedicated to the mechanisms of Multidrug and Extensively Drug-Resistant (MDR and XDR) M. tuberculosis strains emergence 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 have not yet succeeded to solve.

In our laboratory, research is aimed at developing new approaches of antibiotic therapy; 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, both existing and new, are being developed.

According to WHO’s estimates, approximately 10.4 new tuberculosis cases occured in 2015 with almost 1.8 million deaths (WHO 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 the 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 ones (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). The choice of the optimal antigens is the key challenge in the development of such vaccines (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 may affect the structure of the protein product and change its properties, including antigenic activity. Today intraspecific diversity of M. tuberculosis is not being considered during the design of genetically engineered vaccines. Only sequences of the target genes of the laboratory H37Rv strain are used. It was found on the vaccine strain M. bovis BCG that mutations, that arise 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 the development of a 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 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 is 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, in particular bifidobaceria, 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 MDR and XDR. 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 drugs set. Bedaquiline has recently become the first in more than 40 years new anti-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 is of high importance. They must meet certain requirements: a high anti-mycobacterial activity against both drug-sensitive and MDR M. tuberculosis strains, a new biotarget and a lack of toxicity.

Nevertheless, in addition to the acquired drug resistance, the intrinsic drug resistance exists that shows a low level of antibiotics resistance comparing to the acquired one. When an antibiotic influences the M. tuberculosis cell, it activates transcriptional factors that control expression of genes, whose products are able to modify antibiotics or their targets, to provide efflux of antibiotics or their active derivatives from the bacterial cell. In addition, M. tuberculosis cells have numerous cellular transporters that provide efflux of the antibiotics. 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. The resistome genes as well trigger this phenomenon. 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 acquired drug resistance increases the general level of the pathogen’s drug resistance. Usage of antibiotics in the treatment of tuberculosis co-infections or penetration of antibiotics into food can increase M. tuberculosis drug resistance.

The development of high-level drug resistance, that combines 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.

Since 2010 until the present day, the laboratory personnel are conducting research within the framework of the following grants and contracts:

Russian Foundation for Basic Research

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. (years 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).

The role of  SNPs in specific genes in the formation of drug resistance in Mycobacterium tuberculosis (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 Science Foundation

Whole metagenomic analysis of the enteric microbiota in children with autism spectrum disorder: the search for marker genes compositions (years 2017-2019)

Search for biotargets of azolo[1,2,4,5]tetrazine-based antituberculosis drug-candidates (years 2017-2020)

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-NIH joint programme  (USA-Russia) grant " Toxin-antitoxins and RpsA in TB drug resistance and persistence" (years 2013-2014).

The role of region-specific SNPs in virulence genes in Mycobacterium tuberculosis drug resistance (Ministry of Science and Education state contract, BRICS STI Framework Programme, 2017-2019)

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, February 20-21, 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.

- Seminar “CRISPR-Cas systems in bacteria: evolution, new functions, search for analogues, use for genomic editing” February 08, 2018

- Russian-Italian Workshop April 15, 2018

- NGS 2018 May 17, 2018

- International Forum "Biotechnology: State and Development Prospects" May 23, 2018

- Conference "Pathophysiology, Clinic and the Consequences of Microbiota Disorders" May 26, 2018

- All-Russian scientific-practical conference with international participation "Contemporary issues of TB care in the Russian Federation: consolidation of efforts in the fight against tuberculosis" May 31, 2018 - June 01, 2018

- International Symposium "Astana Biotech 2018" June 12-13, 2018

- 7th International Human Microbiome Consortium (IHMC 2018) June 26-28 2018

- The 43rd FEBS Congress 7-12 july 2018

- International Forum “National Security Week” Conference “Breakthrough Developments and Technologies in the Field of Medical and Food Support for Military Personnel” Army-2018 “August 24”, 2018

- XI International Congress "Neurorehabilitation 2019", Moscow, March 15, 2019.

- I National Congress with international participation “Laboratory technologies in reproductive medicine and neonatology: science to practice”, Moscow, Russia, April 23, 2019

- Conference "Pathophysiology, clinical picture and consequences of microbiota disorders." Symposium I “Microbiota and intestinal permeability - the main pathogenetic factors in the formation of functional and organic diseases of the gastrointestinal tract”, May 25, 2019, Moscow, Russia

- Forum “Russia in the 21st Century Global Challenges, Risks and Decisions” Section “Scientific and technological solutions in countering technological, biogenic, sociocultural threats, terrorism and ideological extremism, cyber threats and other sources of danger for society, the economy and the state”, Moscow, 5 June 6th, 2019

- International Scientific and Practical Forum Russia in the 21st Century: Global Challenges, Risks, and Solutions, Section “Directional Search for Drugs for the Treatment and Prevention of Tuberculosis and Other Socially Significant Infectious Diseases: Fundamental and Practical Aspects”, June 11, 2019, Ekaterinburg, Russia

- All-Russian multiconference with international participation "Biotechnology - the medicine of the future." Section “Human Microbiome: Composition, Key Biomarkers, and Correction Pathologies for Pathology”, Novosibirsk July 1, 2019. From 100.

- The 44th FEBS Congress. Krakow, Poland, July 6-11, 2019

- MNS, 25th july 2019, Marrakesh, Morocco

- II Eurasian Creative Forum Modern Eurasia: Synthesis of Science and Art “The Caspian-the Cradle of Eurasian Civilization” Almaty, Kazakhstan October 15, 2019

-6th International Forum on Clinical Microbiology and Infectious Diseases & 3th Prevention and Control of MDR Summit, Shanghai, China, October 18, 2019.

-II National Congress with international participation “Laboratory technologies in reproductive medicine and neonatology: from science and practice”, Moscow, March 13, 2020.

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 tuberculosis as well as other immunological and oncological disorders. The laboratory personnel set up an efficacious testing panel to screen for serine-threonine protein kinase inhibitors, which became the basis for target-specific screening of new promising drug-candidates. 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 diagnostics 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 M. 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 phosphotransferase Aph VIII (deposited in PDB under the number 4Н05) was determined.

The laboratory staff 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.

As part of the laboratory of genetics of microorganisms, we created a museum containing more than one hundred strains of lactobacilli. 16 strains belonging to the species Lactobacillus rhamnosus, L.fermentum, L.plantarum and L.brevis were sequenced and deposited in GenBank. We study interesting properties of lactobacilli such as antioxidant activity, immunostimulating actvity, GABA production and others. We also develop genotyping of lactobacilli based on toxin-antioxin systems. The main tool for studying lactobacilli. Bifidobacteria, streptomycetes and mycobacteria is bioinformatics analysis. We cloned a number of genes (aminoglycoside phosphatransferase Aph VIII Streptomyces rimosus, subunits of FoF1 ATP synthase Streptomyces fradiae, serine-threonine protein kinases Bifidobacterium longum and toxin-antitoxin B. longum system genes) into E. coli cells. We optimized the conditions for the expression of the cloned genes. We developed methods for isolating recombinant proteins by metal affinity chromatography. We succeeded in isolating proteins in preparative amounts hcih allowed us to study their enzymatic activity. We analyzed CRISPR-Cas systems in Lactobacillus, Bifidobacterium, Mycobacterium. The results were reported at the interinstitutional seminar at the Institute of IOGEN RAS “CRISPR-Cas systems in bacteria: evolution, new functions, searches for analogues, use for genomic editing” ”(http://vigg.ru/news/ news-single / article / press-reliz -pervogo-mezhinstitutskogo-seminara-crispr-cas / and vigg.ru/news/news-single/article/press-reliz-vtorogo-mezhinstitutskogo-seminara-crispr-cas/).

International collaboration

The laboratory of the bacterial genetics is a member of the international consortium TBResist (http://projects.iq.harvard.edu/tbresist/home). The consortium was founded in 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 XDR strains. The consortium has a database of over 800 M. tuberculosis isolates’ whole-genome sequences, accompanied by a detailed case-history and treatment outcomes. An agreement has been signed recently with Rouen University in France to pursue joint research in the field of "Human microbiome – Gut-Brain communication" 2017-2022. A project has been prepared for the creation of a joint Russian-French laboratory.

Main publications 2015 - 2020:

1. Алексеева М.Г., Мирончева Т.А., Мавлетова Д.А., Елизаров С.М., Захаревич Н.В., Даниленко В. Н..Биохимическая и структурная характеристика F0F1-АТФ-синтазы Streptomyces fradiae АТСС 19609/ Биохимия, 2015, № 3, С. 358-373

2. 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. 2015, V.24 (7), P. 2926-2938.

3. 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.

4. 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.

5. 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.

6. 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

7. Беляева Е.А., Червинец Ю.В., Червинец В.М., Трошин А.В., Миронов А.Ю., Незаметдинова В.З., Аверина О.В., Даниленко В.Н. Характеристика пробиотических свойств штаммов рода bifidobacterium, Выделенных из желудочно-кишечного тракта жителей центрального региона России / Клиническая лабораторная диагностика. 2015. Т. 60. № 2. С. 53-58.

8. 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.

9. 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.

10. 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

11. 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

12. 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

13. Алексеева М.Г., Мавлетова Д.А., Колчина Н.В., Незаметдинова В.З., Даниленко В.Н.  Выделение и очистка рекомбинантных белков серин-треониновых протеинкиназ штамма Bifidobacterium longum B379M и изучение их активности. / БИОХИМИЯ, 2015, том 80(10), с. 1579 – 1588

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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

20. Ватлин А.А., Беккер О.Б., Лысенкова А.М.,Королев А.М., Щекотихин А.Е., Даниленко В.Н. Секвенирование и анализ резистома Streptomyces fradiae ATCC19609 с целью разработки тест-системы для скрининга новых антибактериальных веществ// Генетика, 2016, Т.52, № 6, С. 723-727

21. 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.

22. 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. C. 1-8.

23. Юнес, Р.А., Полуэктова Е.У., Дьячкова М.С., Козловский Ю.Е., Орлова В.С., Даниленко В.Н. Отбор бактерий-симбионтов рода Lactobacillus и Bifidobacterium по их способности синтезировать гамма-аминомасляную кислоту – один из подходов в получении психобиотиков // Вестник Российского университета дружбы народов. Серия: Экология и безопасность жизнедеятельности. 2016. - № 4 – С. 67-79.

24. Червинец В.М., Червинец Ю.В., Беляева Е.А., Лебедев С.Н., Чаркова А.Р., Трошин А.В., Даниленко В.Н., Урдабаев Ж.К., Жарасов М.Ж., Зевалкина Е.В. Сравнительная характеристика лактобацилл, выделенных из фекалий здоровых людей, проживающих в Российской Федерации и Казахстане // Современные проблемы науки и образования. – 2016. – № 6.

25. 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

26. 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.

27. Аверина О.В., Даниленко В.Н. (Обзор) Микробиота кишечника человека: роль в становлении и функционировании нервной системы/ Микробиология, 2017, 86(1): 5-24

28. Маслов Д.А., Беккер О.Б., Алексеева М.Г., Князева Л.М., Мавлетова Д.А., Афанасьев И.И., Василевич Н.И., Даниленко В.Н. Ингибиторы серин-треониновых протеинкиназ классов аминопиридинов и аминопиримидинов - кандидаты в препараты для лечения лекарственно-устойчивых форм туберкулеза/ ВЕСНИК РГМУ, 2017, 1:42-47

29. Шур К.В., Маслов Д.А., Беккер О.Б., Даниленко В.Н. Генотипирование клинических изолятов Mycobacterium tuberculosis, выделенных в московском регионе, методом MIRU-VNTR / ВЕСНИК РГМУ, 2017, 1:48-51

30. 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

31. Ковтун А.С., Алексеева М.Г., Аверина О.В., Даниленко В.Н. Идентификация аминогликозидфосфотрансфераз клинических штаммов бактерий в микробиоте жителей России/ ВЕСНИК РГМУ, 2017, 2:14-19

32. Захаревич Н.В., Даниленко В.Н. Серин-треориновые протеинкиназы бактерий- потенциальная мишень для регуляции состава микробиоты человека/ ВЕСНИК РГМУ, 2017, 2:20-29

33. 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, 9 (4): 887-899.

34. 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.

35. Нежинская Г.И., Ермоленко Е.И., Евдокимова Н.Р., Шабанов П.Г., Даниленко В.Н., Суворов А.Н. Влияние количественного содержания бактерий на иммунотоксичность пробиотических препаратов / Медицинская иммунология. 2017. Т. 19. № S. С. 70.

36. Klimina, K.M., Poluektova, E.U., Danilenko, V.N. Bacterial toxin–antitoxin systems: Properties, functional significance, and possibility of use (Review) / Applied Biochemistry and Microbiology, 2017, Vol. 53, No. 5, pp. 494–505.

37. Shur K. V., Maslov D. A., Mikheecheva N. E., Akimova N. I., Bekker O. B., Danilenko V. N. The Intrinsic Antibiotic Resistance to β-Lactams, Macrolides, and Fluoroquinolones of Mycobacteria Is Mediated by the whiB7 and tap Genes / Russian Journal of Genetics, 2017, Vol. 53, No. 9, p. 1006–1015.

38. Bekker O.B., Vatlin A.A., Lysenkova L.N., Shchekotikhin A.E., Danilenko V.N. Draft genome sequencing and analysis of mutations of Streptomyces fradiae strain ATCC19609-Olg4R, resistant to (33S)-33-deoxy-33-thiocyanatooligomycin А / Russian Journal of Genetics, 2017, Vol. 53, No. 9, pp. 1105–1108.

39. Chervinets Y, Chervinets V, Shenderov B, Belyaeva E, Troshin A, Lebedev S, Danilenko V. Adaptation and Probiotic Potential of Lactobacilli, Isolated from the Oral Cavity and Intestines of Healthy People / Probiotics Antimicrob Proteins. 2018, Volume 10, Issue 1, pp 22–33, DOI: 10.1007/s12602-017-9348-9, IF: 1,6

40. Marsova M.V., Abilev S.K., Poluektova E.U., Danilenko V. N. A bioluminescent test system reveals valuable antioxidant properties of lactobacillus strains from human microbiota/ World Journal of Microbiology and Biotechnology, 2018, 34(2):27, doi: 10.1007/s11274-018-2410-2, Q 2; SJR 0,743; IF 2.8

41. Nezametdinova V.Z. Mavletova D.A., Alekseeva M.G., Chekalina M.S., Zakharevich N.V., Danilenko V.N. Species-specific serine-threonine protein kinase Pkb2 of Bifidobacterium longum subsp. longum: Genetic environment and substrate specificity //Anaerobe, 2018, Volume 51, Pages 26-35, doi: 10.1016/j.anaerobe.2018.03.003, Q 2; SJR 1.08; IF 2.84

42. Vatlin AA, Bekker OB, Lysenkova LN, Shchekotikhin AE, Danilenko VN. A functional study of the global transcriptional regulator PadR from a strain Streptomyces fradiae-nitR+bld, resistant to nitrone-oligomycin. / Journal of Basic Microbiology, 2018, Volume 58, Issue 9, Pages 739-746, doi: 10.1002/jobm.201800095, Q 2; SJR 0.529; IF 1.79

43. Zaychikova M., Mikheecheva N., Belay Y., Alekseeva M., Melerzanov A. Single nucleotide polymorphisms of Beijing lineage Mycobacterium tuberculosis toxin-antitoxin system genes: their role in the changes of protein activity and evolution / Tuberculosis, 2018, 112:11-19, doi: 10.1016/j.tube.2018.06.011, Q 2; SJR 1.277; IF 2.72

44. Omelchuk O.A., Lysenkova L.N., Belov N.M., Korolev A.M., Dezhenkova L.G., Grammatikova N.E., Bekker O.B., Danilenko V.N., Shchekotikhin A.E. Synthesis and biological activity of 7(7,11)-hydroderivatives of oligomycin A // Macroheterocycles, 2018, Volume 11, Issue 3, Pages 322-328, doi: 10.6060/mhc180795o, Q 3; SJR 0.304; I F 1.01

45. Omelchuk OA., Belov NM., Tsvetkov VB., Korolev AM., Dezhenkova LG., Grammatikova NE., Lysenkova LN., Bekker OB., Danilenko VN., Shchekotikhin AE. Synthesis and Biological Activity of 16,33-O, O-Diformyl- 16,17-dihydro-16(S),17(R)-dihydroxyoligomycin Aand 33-O-Formyloligomycin A // Macroheterocycles, 2018, 11(2): 181-192, doi: 10.6060/mhc170834o, Q 3; SJR 0.304; I F 1.01

46. Chervinets, Y., Chervinets, V., Shenderov, B., Belyaeva, E., Troshin, A.,Lebedev, S.,Danilenko, V. Adaptation and Probiotic Potential of Lactobacilli, Isolated from the Oral Cavity and Intestines of Healthy People/ Probiotics and Antimicrobial Proteins, 2018,  Volume 10, Issue 1,  Pages 22-33, doi: 10.1007/s12602-017-9348-9, Q3, SJR 0.559; I F 3.05

47. Алексеева М.Г., Рудакова Н.Н., Захаревич Н.В., Мавлетова Д.А., Бойко К.М., Николаева А.Ю., Корженевский Д.А., Даниленко В.Н. Новый ген аминогликозидфосфотрансферазы aph(3'')-Id из Streptomyces rimosus АТСС10970, кодирующий устойчивость к стрептомицину / Генетика, 2018, 54(10):1228-1232, doi: 10.1134/S1022795418100034, Q4; SJR 0,224; I F: 0.51

48. Vatlin A.A, Bekker O.B., Lysenkova L.N., Shchekotikhin A.E., Danilenko V.N. Analysis of Mutations of the Strains of Streptomyces fradiae ATCC 19609-Olg2R Resistant to (33S)-Azido-33-Deoxyoligomycin A/ Russian Journal of Genetics, 2018, Volume 54, Issue 11, 1 Pages 1375-1377, doi: 10.1134/S1022795418110169, Q4; SJR 0.224; I F 0.51

49. Danilenko V.N., Zaychikova M.V., Dyakov I.N., Shur K.V.,Maslov D.A. Mycobacterium tuberculosis: Drug resistance, virulence and possible solutions // Bulletin of Russian State Medical University, 2018, Volume 7, Issue 3, Pages 5-12, doi: 10.24075/brsmu.2018.038, Q 4; SJR 0.11; I F 0.15

50. Zaychikova M.V.,  Zakharevich N.V.,  Chekalina M.S.,  Danilenko V.N CRISPR-as systems of Mycobacterium tuberculosis: The structure, transformation in different lineages in the process of evolution and a possible role in the formation of virulence and drug resistance // Bulletin of Russian State Medical University, 2018, Volume 7, Issue 2, Pages 5-13, doi: 10.24075/brsmu.2018.016, Q 4; SJR 0.11; I F:  0.15

51. Kovtun A.S., Averina O.V., Zakharevich N.V., Kasianov A.S., Danilenko V.N. In silico Identification of Metagenomic Signature Describing Neurometabolic Potential of Normal Human Gut Microbiota// Russian Journal of Genetics, 2018 Volume 54, Issue 9, Pages 1101-1110, doi: 10.1134/S0016675818090084, Q 4; SJR 0.224; I F: 0.51

52. Maslov D.A.,  Bekker O.B.,  Shur K.V.,  Vatlin A.A.,  Korotina A.V.,  Danilenko V.N. Whole-genome sequencing and comparative genomic analysis of mycobacterium smegmatis mutants resistant to imidazo[1,2-b][1,2,4,5]tetrazines, antituberculosis drug candidates // Bulletin of Russian State Medical University, 2018,Volume 7, Issue 3, Pages 19-22, doi: 10.24075/brsmu.2018.039, Q 4; SJR 0.11; I F 0.15

53. Shur K.V., Umpeleva T.V., Bekker O.B., Maslov D.A., Zaychikova M.V., Vakhrusheva D.V., Danilenko V.N. Compilation of the mycobacterium tuberculosis Beijing-b0 lineage sample and identifying predictors of immune dysfunction in source patients// Bulletin of Russian State Medical University, 2018, Volume 7, Issue 3, Pages 23-27, doi: 10.24075/brsmu.2018.040, Q 4; SJR 0.11; I F 0.15

54. Shur K.V., Bekker O.B., Zaichikova M.V., Maslov D.A., Akimova N.I., Zakharevich N.V., Chekalina M.S., Danilenko V.N. Genetic Aspects of Drug Resistance and Virulence in Mycobacterium tuberculosis/ Russian Journal of Genetics 2018, Volume 54, Issue 12, Pages 1385-1396, doi: 10.1134/S1022795418120141, Q4; SJR 0,224; I F 0.51

55. Алексеева М.Г., Мавлетова Д.А., Даниленко В.Н. Тест-система Escherichia coli/aphVIII/gsk3β для селективного скрининга ингибиторов серин-треониновой протеинкиназы GSK3β.//Генетика, 2018, Т.54, приложение с.S14-S17, doi: 10.1134/S0016675818130039, Q4; SJR 0.224; I F: 0.51

56. Klimina, K.; Poluektova E.; Kudryavtseva A.; Kasianov A.; Danilenko V. Type II toxin-antitoxin systems for metagenomic studies/ BIOCHEMISTRY & MOLECULAR BIOLOGY, FEBS OPEN BIO, 2018, Том: 8 Стр.: 451-451, doi:10.1002/2211-5463.12453, WOS:000437674105132, Q4; SJR; I F: 2,36

57. Maslov D. A.; Shur, K. V.; Vatlin, A. A.; Bekker, O. B.; Korotina, A. V.; Rusinov G. L.; Charushin, V. N.; Danilenko, V. N. Search for azolo[1,2,4,5]tetrazines biotargets in mycobacteria/ FEBS OPEN BIO Том: 8  Стр.: 263-263, Q4; SJR; I F: 2,36

58. Chekalina, M.; Danilenko, V. Study of the PFNA cluster in bifidobacteria: structure, evolution and possible functions/ BIOCHEMISTRY & MOLECULAR BIOLOGY, FEBS OPEN BIO, 2018, Том: 8 Стр.: 381-382, Q4, WOS:000437674104224, Q4; SJR; I F: 2,36

59. Omelchuk O.; Mavletova D.; Koshenko T.; Lysenkova L.; Bekker O.; Vatlin A.; Danilenko V.; Shchekotikhin A. ATP-synthase inhibition by semi-synthetic oligomycin A derivatives/ BIOCHEMISTRY & MOLECULAR BIOLOGY, FEBS OPEN BIO, 2018, Том: 8 Стр.: 487-487 WOS:000437674105246, Q4; SJR; I F: 2,36

60. Klimina K., Batotsyrenova E.G., Odorskaya M., Yunes R., Kasyanov A., Danilenko V. Analysis of gut microbiota diversity and physiological parameters in different light/dark cycles / Translating microbiome science IHMC 2018 Book of Abstracts. 2018. С. 193. / 7TH INTERNATIONAL HUMAN MICROBIOME CONSORTIUM MEETING, Killarney, Ireland, 26-28 июня 2018 г.

61. Dyachkova MS, Chekalin EV, Danilenko VN. Positive Selection in Bifidobacterium Genes Drives Species-Specific Host-Bacteria Communication // Frontiers in Microbiology 2019 Oct 15; 10:2374., doi: 10.3389/fmicb.2019.02374. eCollection 2019., Q1; SJR 1.63; IF 4.019

62. Liu J., Shi W., Zhang S., Hao X., Maslov D.A., Shur K.V., Bekker O.B., Danilenko V.N., Zhang Y. Mutations in efflux pump Rv1258c (Tap) cause resistance to pyrazinamide, isoniazid and streptomycin in M. tuberculosis// Frontiers in Microbiology, 2019, V.10., P.1., doi.org/10.3389/fmicb.2019.00216, Q 1, SJR 1.21; I F 4.259

63. Maslov DA, Korotina AV, Shur KV, AA. Vatlin, Bekker OB, Tolshchina SG, Ishmetova RI, Ignatenko NK, Rusinov GL, Charushin VN, Danilenko VN. Synthesis and antimycobacterial activity of imidazo[1,2-b][1,2,4,5]tetrazines. // European Journal of Medicinal Chemistry, 2019, 2019 May 31;178:39-47. doi: 10.1016/j.ejmech.2019.05.081, Q1; SJR 1.21; IF 4.833

64. Fetissov S.O., Averina O.V., Danilenko V.N. Neuropeptides in the microbiota-brain axis and feeding behavior in autism spectrum disorder// Nutrition, 2019, V. 61., P. 43-48, https://doi.org/10.1016/j.nut.2018.10.030, Q2, SJR 2.18; I F 3.568

65. Klimina KM, Kasianov AS, Poluektova EU, Emelyanov KV, Voroshilova VN, Zakharevich NV, Kudryavtseva AV, Makeev VJ, Danilenko VN. Employing toxin-antitoxin genome markers for identification of Bifidobacterium and Lactobacillus strains in human metagenomes. // PeerJ, 2019., 7: e6554, doi: 10.7717/peerj.6554, Q2; SJR1.04; IF 2.118

66. Alekseeva M.G., Boyko K.M., Nikolaeva A.Yu, Mavletova D.A., Rudakova N.N., Zakharevich N.V., Korzhenevskiy D.A., Ziganshin R.H., Popov V.O., Danilenko V.N. Identification, functional and structural characterization of novel aminoglycoside phosphotransferase APH(3'')-Id from Streptomyces rimosus subsp. rimosus ATCC 10970. // Archives of Biochemistry and Biophysics, 2019, 671, P. 111-122., doi: 10.1016/j.abb.2019.06.008, Q2, SJR 1.15; IF 3.118

67. Klimina KM, Batotsyrenova EG, Yunes RA, Gilyaeva EH, Poluektova EU, Kostrova TA, Kudryavtseva AV, Odorskaya MV, Kashuro VA, Kasianov AS, Ivanov MB, Danilenko VN. The effects of desynchronosis on the gut microbiota composition and physiological parameters of rats. // BMC Microbiology 2019 Jul 12;19(1):160. doi: 10.1186/s12866-019-1535-2. Q 2; SJR 1.27; IF 3.287

68. Yunes R.A., Poluektova E.U., Vasileva E.V., Odorskaya M.V., Marsova M.V., Kovalev G.I., Danilenko V.N. A Multi-strain Potential Probiotic Formulation of GABA-Producing Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 with Antidepressant Effects. //Probiotics Antimicrob Proteins. 2019 Nov 1. doi: 10.1007/s12602-019-09601-1. Q 2, SJR 0.56; IF 2.962

69. Lysenkova LN, Saveljev OY, Omelchuk OA, Zatonsky GV, Korolev AM, Grammatikova NE, Bekker OB, Danilenko VN, Dezhenkova LG, Mavletova DA, Scherbakov AM, Shchekotikhin AE. Synthesis, antimicrobial and antiproliferative properties of epi-oligomycin A, the (33S)-diastereomer of oligomycin A.// Natural Product Research, 2019 May 10:1-9. doi: 10.1080/14786419.2019.1608540, Q 2; SJR 0.602; IF 1.999

70. Danilenko V.N. Developing a Technological Platform to Create Innovative TB Drugs Active against Multidrug-Resistant Strains// Herald of the Russian Academy of Sciences, 2019, Vol. 89, No. 2, pp. 144–150. doi: 10.1134/S1019331619020035, Q3; SJR 0.277; IF 0.492

71. Maslov D.A., Shur K.V., Vatlin A.A., Danilenko V.N. MmpS5/MmpL5 efflux pump provides imidazo[1,2-b] [1,2,4,5] tetrazine resistance to Mycobacterium smegmatis. // FEBS Open Bio 2019; 9 (Suppl. 1) Pp. 118. doi: 10.1002/2211-5463.12675, Q 4; SJR 0.75; IF 2.126

72. Zakharevich N.V., Nezametdinova V.Z., Averina O.V., Chekalina M.S., Alekseeva M.G., Danilenko V.N. Complete Genome Sequence of Bifidobacterium angulatum GT102: Potential Genes and Systems of Communication with Host // Russian Journal of Genetics, 2019, Volume 55, Issue 7, 1 July 2019, Pages 847-864, doi: 10.1134/S1022795419070160, Q4, SJR 0.224; IF 0.982

73. Захаревич Н. В., Аверина О. В., Незаметдинова В. З., Даниленко В. Н. ПОЛНЫЙ ГЕНОМ Bifidobacterium angulatum GT102. I. ПОТЕНЦИАЛЬНЫЕ ГЕНЫ И ГЕННЫЕ КЛАСТЕРЫ, УЧАСТВУЮЩИЕ ВО ВЗАИМОСВЯЗИ С КЛЕТКАМИ ХОЗЯИНА. // Генетика, 2019, том 55, № 8, с. 876–886. doi: 1134/S0016675819070166, Q 4; SJR 0.224; IF 0.982

74. Незаметдинова В.З., Захаревич Н.В., Аверина О.В., Чекалина М.С., Алексеева М.Г., Даниленко В.Н. Полный геном Bifidobacterium angulatum GT102. II. Системы сигнальной трансдукции и адаптивные гены. // Генетика, 2019, том 55, № 9, с. 1021-1030, doi: 10.1134/S0016675819090108, Q 4; SJR 0.224; IF 0.982

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