АНТИБИОТИКОРЕЗИСТЕНТНОСТЬ БАКТЕРИАЛЬНЫХ ПАТОГЕНОВ ПРИ ИНФЕКЦИЯХ НИЖНИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ

В этой статье представлен обзор научных статей по проблеме устойчивости микроорганизмов к антибиотикам Обобщены современные представления об антибиотикорезистентности, разделения микроорганизмов на чувствительные и устойчивые к действию антибиотиков, раскрыто понятие минимальной ингибирующей концентрации с современных позиций. Раскрыты основные механизмы развития антибиотикорезистентности, устойчивости, векторы и гены, отвечающие за передачу резистентности. Резистентность микроорганизмов к антибактериальным средствам может быть врождённой и приобретенной. Описаны бактериальные возбудителями ИНДП Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis и другие грамположительные и грамотрицательные бактерии. Показаны механизмы ненаследственной устойчивости, которые включают изменение метаболической активности, фенотипическую пластичность, образование пленок. Факторы в приобретении и передаче антибиотикорезистентности. Эволюцию антибиотикорезистентности, которая проходит несколько ключевых этапов. Одним из векторов в изучении эволюции антибиотикорезистентности должен стать анализ не изолированных бактериальных штаммов, бактериальных сообществ, формирующих биоплёнки, поскольку, находясь в биоплёнках микроорганизмы проявляют низкую чувствительность к различным антибиотикам за счёт механизмов фенотипической устойчивости.
Методы борьбы с АР включающая несколько направлений: рациональное использование антибиотиков, разработка новых антибиотиков, вакцинация

1. Lynch J.P. 3rd, Clark N.M., Zhanel G.G. Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum beta-lactamases and carbapenemases). Expert Opin. Pharmacother. 2013;14(2):199–210.

2. Andersson D.I., Hughes D. Microbiological effects of sublethal levels of antibiotics. Nat. Rev. Microbiol. 2014;12(7):465–78.

3. Blair J.M., Webber M.A., Baylay A.J., Ogbolu D.O., Piddock L.J. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 2015;13(1):42–51.

4. Viswanathan VK. Off-label abuse of antibiotics by bacteria. Gut Microbes. 2014;5(1):3–4. doi: 10.4161/gmic.

5. Morrissey I., Oggioni M.R., Knight D., Curiao T., Coque T., Kalkanci A., Martinez J.L. Evaluation of Epidemiological Cut-Off Values Indicates that Biocide Resistant Subpopulations Are Uncommon in Natural Isolates of Clinically-Relevant Microorganisms. (2014). Public Library of Science ONE 9(1): e86669.

6. Logre E., Denamur E., Mammeri H. Contribution to Carbapenem Resistance and Fitness Cost of DcuS/DcuR, RcsC/RcsB, and YehU/YehT Two-Component Systems in CTX-M-15-Producing Escherichia coli. Microb. Drug Resist. 2019 Oct 9. doi: 10.1089/mdr.2019.0027

7. Martinez J.L. General principles of antibiotic resistance in bacteria. Drug Discovery Today: Technologies. 2014;1: 33-9.

8. Boto L., Martinez J.L. Ecological and temporal constraints in the evolution of bacterial genomes. Genes. 2011;2:804–28.

9. Hiltunen T., Virta M., Laine A.L. Antibiotic resistance in the wild: an eco-evolutionary perspective. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2017 Jan 19;372(1712). pii: 20160039. Review. PubMed. PMID: 27920384; PubMed Central PMCID: PMC5182435.

10. Vinogradova K.A., Bulgakova V.G., Pauline A.N., Kozhevin P.A. The resistance ofmicroorganisms to antibiotics: resistoma, its volume, diversity and development. Antibiotiki I khimioterapiya. 2013; 58 (5-6): 38-48. (in Russian)

11. Canton R., Gonzalez-Alba J.M., Galan J.C. CTX-M Enzymes: Origin and Diffusion. Frontiers in Microbiology. 2012;3:110.

12. Zemlyanko O.M., Rogoza T.M., Zhuravleva G.A. Mechanisms of multiple resistance of bacteria to antibiotics. Ekologicheskaya genetika. 2018 (3): 4-10. (in Russian)

13. Dubiley S.A., Ignatov A.N., Shemyakin I.G. Molecular genetic methods for the identification of drug resistance of Mycobacterium tuberculosis. Molekulyarnaya genetika, mikrobiologiya I virusologiya. 2005 (1): 3-4. (in Russian)

14. Olicares J., Bernardini A., Garcia-Leon G., Corona F., Sanchez M.B., Martinez J.L. The intrinsic resistome of bacterial pathogens. Frontiers in Microbiology. 2013 Apr 30;4:103.

15. Hernando-Amado S., Sanz-Garcia F., Martinez J.L. Antibiotic Resistance Evolution Is Contingent on the Quorum-Sensing Response in Pseudomonas aeruginosa. Molecular biology and evolution. 2019 Oct 1;36(10):2238-51. doi: 10.1093/molbev/msz144. PubMed PMID:31228244.

16. Balaban N.Q., Merrin J., Chait R., Kowalik L., Leibler S. Bacterial persistence as a phenotypic switch. Science. 2004;305(5690):1622–5.

17. Allison K.R., Brynildsen M.P., Collins J.J. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature. 2011;473(7346):216–20.

18. Grant S.S., Kaufmann B.B., Chand N.S., Haseley N., Hung D.T. Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(30):12147–52.

19. Martinez J.L. Bottlenecks in the transferability of antibiotic resistance from natural ecosystems to human bacterial pathogens. Frontiers in microbiology. 2011;2:265.

20. Cabello F.C., Godfrey H.P., Tomova A., Ivanova L., Dolz H., Millanao A., Buschmann A.H. Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health. Environmental microbiology. 2013;15(7):1917–42.

21. Olivares J., Alvarez-Ortega C., Linares J.F., Rojo F., Kohler T., Martinez J.L. Overproduction of the multidrug efflux pump MexEF-OprN does not impair Pseudomonas aeruginosa fitness in competition tests, but produces specific changes in bacterial regulatory networks. Environmental microbiology. 2012;14(8):1968–81.

22. Gullberg E., Cao S., Berg O.G., Ilback C., Sandegren L., Hughes D., Andersson D.I. Selection of resistant bacteria at very low antibiotic concentrations. Public Library of Sciences. 2011;7(7):e1002158.

23. Martinez J.L. Natural antibiotic resistance and contamination by antibiotic resistance determinants: the two ages in the evolution of resistance to antimicrobials. Frontiers in microbiology. 2012;3:1

24. Martinez J.L. The role of natural environments in the evolution of resistance traits in pathogenic bacteria. Proceedings. Biological sciences. 2009;276(1667):2521– 30.

25. Martinez J.L., Sanchez M.B., Martinez-Solano L., Hernandez A., Garmendia L., Fajardo A. Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. Federation of European Microbiological Societies. 2009;33(2):430–49.

26. Poole K. Efflux-mediated antimicrobial resistance. J. Antimicrob. Chemother. 2015. 56:20-51.

27. Baltz R.H. Marcel Faber Roundtable: is our antibiotic pipeline unproductive because of starvation, constipation or lack of inspiration? J. Ind. Microbiol. Biotechnol. 2016; 33:507-13.

28. Projan S. J. Why is big pharma getting out of antibacterial drug discovery? Curr. Opin. Microbiol. 2013. 6:427-30.

29. Martinez J.L. Bottlenecks in the transferability of antibiotic resistance from natural ecosystems to human bacterial pathogens. Frontiers in microbiology. 2011;2:265.

30. Cabello F.C., Godfrey H.P., Tomova A., Ivanova L., Dolz H., Millanao A., Buschmann A.H. Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health. Environmental microbiology. 2013;15(7):1917–42

31. Olivares J., Alvarez-Ortega C., Linares J.F., Rojo F., Kohler T.,Martinez J.L. Overproduction of the multidrug efflux pump MexEF-OprN does not impair Pseudomonas aeruginosa fitness in competition tests, but produces specific changes in bacterial regulatory networks. Environmental microbiology. 2012;14(8):1968–81.

32. Gullberg E., Cao S., Berg O.G., Ilback C., Sandegren L., Hughes D., Andersson D.I. Selection of resistant bacteria at very low antibiotic concentrations. Public Library of Sciences. 2011;7(7):e1002158.

33. Martinez J.L. Natural antibiotic resistance and contamination by antibiotic resistance determinants: the two ages in the evolution of resistance to antimicrobials. Frontiers in microbiology. 2012;3:1

34. Martinez J.L. The role of natural environments in the evolution of resistance traits in pathogenic bacteria. Proceedings. Biological sciences. 2009;276(1667):2521–30.

35. Martinez J.L., Sanchez M.B., Martinez-Solano L., Hernandez A.,Garmendia L., Fajardo A. Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. Federation of European Microbiological Societies. 2009;33(2):430–49.

36. Bush K. Proliferation and significance of clinically relevant betalactamases. New York Academy of Sciences 2013;1277:84–90.

37. Poole K. Efflux-mediated antimicrobial resistance. J. Antimicrob. Chemother. 2015. 56:20-51.