AP19679239 Proteogenomic analysis of enterotoxigenic strains of Bacteroides fragilis

Relevance

The gram-negative bacillus Bacteroides fragilis, one of numerous microorganisms inhabiting the human gastrointestinal tract, is the most common cause of anaerobic infections. Currently, it is customary to distinguish two of its molecular subtypes: nontoxigenic B. fragilis (NTBF) and enterotoxigenic B. fragilis (ETBF). The ETBF variant is also often associated with inflammatory diseases of the human intestine.

Antimicrobials are still an important medical resource for the effective treatment of various diseases, although bacterial resistance has increased significantly in recent years. According to the researchers, a significant contribution to the increase in resistance is made by sub-inhibitory concentrations of antimicrobial agents. Most studies in the world concern interactions between antibiotics and microorganisms in vitro, whereas there is very little information about antibiotic-bacterial interaction in vivo.

Also, in recent years, the attention of researchers has been attracted by (OMV) of bacteria due to the latter’s participation in giving resistance to antimicrobials by removing harmful agents from the cell. In this connection, the study of the effect of sub-inhibitory concentrations of carbapenem antibiotics on the production of outer membrane vesicles in B. fragilis in an animal model is relevant.

Purpose

To study the effect of carbapenem antibiotics on the bacterial overproduction of outer membrane vesicles in Bacteroides fragilis.

Expected results

The presented project will solve a fundamental problem, as new data will be obtained on bacterial-drug interactions in vivo in response to the effects of sub-inhibitory concentrations of carbapenem antibiotics. All this will allow us to better understand the role of outer membrane vesicles in the emergence of resistance in Bacteroides fragilis to antimicrobial drugs.

  • scope and target consumers of each expected result:

This project has a fundamental direction. The target consumers are researchers and students with biological and medical profiles.

  • influence of expected results on the development of the main scientific direction and related fields of science and technology:

The results obtained during the implementation of the project will allow us to better understand the role of outer membrane vesicles in the emergence of resistance in Bacteroides fragilis to antimicrobial drugs of the carbapenem series.

  • applicability and (or) the possibility of commercialization of the obtained scientific results:

The research is fundamental.

  • social, economic, environmental, scientific and technical, multiplicative, and (or) other effects of the project results with justification:

The new knowledge gained during the project will allow us to better understand bacterial-drug interactions in vivo in response to taking sub-inhibitory concentrations of carbapenem.

Head of research

Kozhakhmetova Saniya Sattybayevna, Candidate of Biological Sciences, Senior Researcher of the National Scientific Shared Laboratory of Biotechnology of LLС “National Center of Biotechnology” of the Ministry of Health of the Republic of Kazakhstan. Hirsch index (h-index) in the Scopus database – 3. Scholarship holder of the State Scientific Scholarship for Talented Scientists (2010-2011 y). She mastered molecular genetic methods in the scientific centers of neighboring countries. Specialist in microbiology. The responsible executor of the project AP05130984 “Study and evaluation of antibiotic sensitivity to a wide range of antibiotics of the bacterial group Bacteroides fragilis in patients with intraabdominal infections”,  2018-2020 y, and also the responsible executor of the AP09258813 project “A multi-genomic approach to the study of the cellular response of Bacteroides fragilis to carbapenems”, 2021-2023 yy. The presented project is a continuation of the above projects and will be aimed at investigating the role of the outer membrane vesicles of Bacteroides fragilis in the development of a pathological infectious process in an animal model, as a result of exposure to sub-inhibitory concentrations of carbapenem antibiotics.

In the project, Kozhakhmetova Saniya Sattybayevna will lead the project, control all work related to the implementation of the project, and also carry out microbiological work, including cultivation, obtaining carbapenem-resistant mutants, and determining the concentration of cytokines in the blood. In addition, she will prepare reports and publish the main results of the study.

Research team members

Researcher 1 – Zholdybaeva Elena Vitalievna.Candidate of Biological Sciences, Associate Professor, Head of the National Scientific Shared Laboratory of Biotechnology. Hirsch index (h-index) in the Scopus database – 9 (https://www.scopus.com/authid/detail.uri?authorId=55640278400 ). A specialist in the field of genomic research and population genetics. Author of more than 80 scientific papers, including 19 with non-zero impact factor, on the Web of Science and Scopus databases. Responsible executor of the project AP05130984 “Study and evaluation of antibiotic sensitivity to a wide range of antibiotics of the bacterial group Bacteroides fragilis in patients with intraabdominal infections”,  2018-2020 y., head of the research of the AP09258813 project “A multi-genomic approach to the study of the cellular response of Bacteroides fragilis to carbapenems”, 2021-2023 y. In the presented project, she will conduct molecular genetic research.

Researcher 2 – Bekbayeva Ayazhan, Master of the Natural Sciences, junior researcher of LLP “National Center of Biotechnology” of the Ministry of Health of the Republic of Kazakhstan. Hirsch index (h-index) in the Scopus database –1. A. Bekbaeva will participate in the preparation of samples for genetic analysis.

Researcher 3 – Tarlykov Pavel Viktorovich, PhD, Associate Professor, Head of the Laboratory of Proteomics and Mass Spectrometry of the LLP “National Center of Biotechnology” of the Ministry of Health of the Republic of Kazakhstan. Hirsch index (h-index) in the Scopus database – 9. A specialist in the fields of biomedicine, proteomics, genomics, and molecular biology. Author of more than 140 scientific publications, including more than 20 with an impact factor. He will perform proteomics studies for the project.

Researcher 4 – Auganova Dana, Master of Natural Sciences, junior researcher of, LLP “National Center of Biotechnology” of the Ministry of Health of the Republic of Kazakhstan. Hirsch index (h-index) in the Scopus database –1. Dana is proficient in proteomic research methods. She will be involved sample preparation for proteomics studies in the project.

Researcher 5 – Krivoruchko Tatyana Nikolaevna, Researcher at the Toxicology and Pharmacology Laboratory of the NCB. Tatyana has experience working with laboratory animals (mice, guinea pigs, rabbits), owns biochemical, hemostasiological, physiological research methods. She is responsible for working with laboratory animals, manipulating laboratory animals, modeling infections, and taking biomaterial for research in this project.

Researcher 6 – Dashevskaya Natalia Viktorovna, accredited veterinarian, she is proficient in biochemical, hemostasiological, physiological research methods. She is responsible for the proper maintenance of laboratory animals in the vivarium, organization of work with laboratory animals, control of manipulations with laboratory animals, euthanasia of laboratory animals for the project.

Researcher 7 – Surgeon at the state-owned public enterprise with the rights of economic management « City Hospital No. 1» of the Astana city. He will collect samples to form a collection of bacteroids.

Researcher 8 – histologist. In the project, he will conduct histological studies.

Publications of the project supervisor and members of the research group related to the project topic

  1. Kozhakhmetova S., Zholdybayeva E., Tarlykov P., Atavliyeva S., Syzdykov T., Daniyarov A., Mukhtarova K., Ramankulov Y. Determinants of resistance in Bacteroides fragilis strain BFR_KZ01 isolated from a patient with peritonitis in Kazakhstan // Journal of Global Antimicrobial Resistance, 2021, 25, page 1–4 pp. doi.org/10.1016/j.jgar.2021.02.022. Индекс цитирования – 2. Scopus: CiteScore – 5.6, пpoцeнтиль -55.
  2. Zholdybayeva E., Kozhakhmetova, S., Atavliyeva, S.,Tarlykov, P.,Ramankulov, Y. Draft Genome Sequence of a Bacteroides fragilis Strain Isolated from Peritoneal Fluid of a Patient from Kazakhstan// Microbiol Resour Announc., 2020, 25;9(26):e00377-20. doi: 10.1128/MRA.00377-20. Индекс цитирования – 0. Scopus: CiteScore – 1.5, пpoцeнтиль -40.
  3. Kozhakhmetov S., Babenko D., Kozhakhmetova S., Tuyakova A., Nurgaziyev M., Nurgozhina A., Muhanbetganov N., Chulenbayeva L., Sergazy Sh., Gulyayev A., Aljofan M., Kushugulova A.  Therapeutic Potential of Metabolites from Lactobacillus rhamnosus and Mare’s Milk in the Treatment of Dysbiosis // BioMed Research International, 2022, page 1-8 pp. doi.org/10.1155/2022/3851478. Индекс цитирования – 1. Scopus: CiteScore – 4.7, пpoцeнтиль -67.
  4. Kozhakhmetova S.S., Kassymbek K.T., Zholdybayeva E.V. Multi-omics approach to the study of microorganisms // Experimental Biology, 2021, 4(89),  page 21-31 pp. doi.org/10.26577/eb.2021.v89.i4.03.
  5. Kozhakhmetova S.S., Zholdybayeva E.V., Mukhtarova K.E., Ramankulov Ye.M. Pathogenicity factors and antibiotic resistance of the Bacteroides fragilis// Eurasian Journal of Applied Biotechnology, 2020, 1,  page: 3-13 pp. doi: 10.11134/btp.1.2020.1
  6. Кoжaхмeтoвa C.C., Жoлдыбaeвa E.В., Тapлыкoв П.В., Aтaвлиeвa C.Ш., Cыздкoв Т.A., Хaceнoв P.E., Мухтapoвa К.E., Paмaнкулoв E.М.  Пpoфили чувcтвитeльнocти и гeны уcтoйчивocти к aнтибиoтикaм шиpoкoгo cпeктpa дeйcтвия у Bacteroides fragilis, изoлиpoвaнных из бoльниц г.Нуp-Cултaн  //Acтaнa Мeдицинaлық жуpнaлы 2020, №1, cтp.29-32.

Achieved results

2023 y.

At this stage of the project, clinical material is being collected from Kazakhstan patients with intra-abdominal diseases, as well as the formation of a collection of Bacteroides fragilis isolates.