The Mechanisms of Antibiotic Resistance in Bacteria of The Genus Campylobacter

Antibiotic resistance of bacteria that contaminate raw food products is currently one of the most acute public health problems. The widespread use of antibiotics for therapeutic or prophylactic purposes in veterinary medicine and as growth promoters for farm animals and poultry creates the conditions for selective pressure on bacterial populations, leading to their adaptation and dissemination of antibiotic- resistant strains of emergent foodborne pathogens, including bacteria of the genus Campylobacter. According to the WHO, campylobacteriosis gastroenteritis retains its leading position among the acute foodborne infections. The article analyzes the features of genetic transformation and formation of resistance of Campylobacter bacteria to several classes of antimicrobial drugs, most commonly used in medicine and veterinary. It is shown that Campylobacter spp. have multiple ways to enhance resistance, which include horizontal DNA transfer (through the mechanism of natural transformation), plasmid transfer of resistance genes and chromosomal mutations. The article presents the data on specific mechanisms of Campylobacter jejuni antibiotic resistance to fluoroquinolones, tetracyclines, aminoglycosides, and macrolides. It is shown that the expression of resistance in Campylobacter spp. is the most pronounced in relation to tetracyclines, which in recent years has led to a rapid increase to 61—87% of the proportion of tetracycline-resistant strains among the populations of campylobacters, contaminating food products. The analysis of data confirming the transfer of resistance genes and total resistance of Ñ.jejuni to fluoroquinolones, which was formed as a result of prolonged exposure to sublethal doses of these drugs, was carried out. The tendency of Ñ.jejuni to form resistance to macrolides, primarily to erythromycin, caused not only by chromosomal mutations, but also by the presence of transmissive plasmid resistance, is now considered as a serious threat to public health. The search for new informative antibiotic resistance markers of Campylobacter spp. will allow making prognostic assessment of the risk of formation of resistance of campylobacteriosis pathogens to the most frequently used antimicrobial agents.

1. World Health Organization. The global view of campylobacteriosis: report of an expert consultation, Utrecht, Netherlands, 9—11 July 2012.//TSBN 978 92 4 156460 1. www.who.int

2. Campylobacter Ecology and Evolution./ 2014, Caister Academic Press, Norfolk, UK, edited by S.K. Sheppard. 359, ISBN: 978-1-908230-2.

3. Nachamkin I., Guerry P. Campylobacter infections. Foodborne Pathogens: Microbiology and Molecular Biology. Wymondham, 2005; 285-293.

4. Wieczorek K., Osek J. Antimicrobial Resistance Mechanisms among Campylobacter. BioMed Research International 2013; 2013: 1—12.

5. John E., Moore N, Barton M.D. The epidemiology of antibiotic resistance in Campylobacter. Microb Infect 2006; 8:1955—1966.

6. European Food Safety Authority and European Centre for Disease Prevention and Control. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2014. EFSA J 2016; 14: 2: 4380. www.efsa.europa.eu/efsajournal.

7. MavriA., Ribic V., Mozjna S.S. The Biocide and Antibiotic Resistance in Campylobacter jejuni and Campylobacter coli. Emerging and Traditional Technologies for Safe, Healthy and Quality Food 2015; 269—283.

8. Виноградова К.А., Булгакова В.Т., Полин А.Н., Кожевин ПА. Устойчивость микроорганизмов к антибиотикам: резистома, её объем, разнообразие и развитие. Антибиотики и химиотер. — 2013. — Т. 58. - № 5-6, С. 38-48. / Vinogradova К.А., Bulgakova V.G., Polin AN., Kozhevin P.A. Ustoychivost' mikrootganizmov k antibiotikam: rezistoma, ее ob"em, raznoobrazie i razvitie. Antibiotiki i khimioter 2013; 58: 5-6: 38-48. [in Russian]

9. Aminov R.I. and Mackie R.I. Evolution and ecology of antibiotic resistance genes. FEMS Microbiol Lett 2007; 271: 2: 147—161.

10. Monier J.-M., Demanèche S, Delmont T.O. et al. Metagenomic exploration of antibiotic resistance in soil. Curr Opin Microbiol 2011; 4: 3: 236—243.

11. Bae J., Oh E., Jeon B. Enhanced transmission of antibiotic resistance in Campylobacter jejuni biofilms by natural transformation. Antimicrob Agents Chemother 2014; 58: 12: 7573—7575.

12. Gangaiah D., Kassem I.I., Liu Z., Rajashekara G. Importance of polyphosphate kinase 1 for Campylobacter jejuni viable-but-nonculturable cell formation, natural transformation, and antimicrobial resistance. Applied Environ Microbiol 2009. — vol.75. — No 24. —p.7838—7849.

13. Alfredson D.A., Korolik V. Antibiotic resistance and resistance mechanisms in Campylobacter jejuni and Campylobacter coli./ FEMS Microbiol Lett 2007; 277: 123—132.

14. Wang Y., Dong Y., Deng F., Liu D.,Yao H., Zhang Q.et al. Species shift and multidrug resistance of Campylobacter from chicken and swine, China, 2008-14. J Antimicrob Chemother 2016; 71: 666—669.

15. Iovine N.M. Resistance mechanisms in Campylobacter jejuni. Virulence 2013; 4: 3: 230—240.

16. Acheson D., Allos B. M. Campylobacter jejuni infections: update on emerging issues and trends. Clin Infect Dis 2001; 32: 8: 1201—1206.

17. Man S.M. The clinical importance of emerging Campylobacter species. Natur Rev Gastroenterol Hepatol 2011; 8: 12: 669—685.

18. Ефимочкина H.P., Короткевич Ю.В., Стеценко В.В., Пичугина Т.В., Быкова КБ., Минаева Л.П., Шевелева С.А. Антибиотикорезистентность штаммов Campylobacter jejuni, выделенных из пищевых продуктов. Вопросы питания. — 2017. — № 1. — С.18—28. /EfimochkinaN.R., KorotkevichYu.V., StetsenkoV.V., Pichugina T.V., BykovaLB., Minaeva L.P., SHeveleva S.A. Antibiotikorezistentnost' shtammov Campylobacter jejuni, vydelennykh iz pishchevykh produktov. Voprosy pitaniya 2017; 1: 18—28. [in Russian]

19. McDermott P.E., Bodeis S.M., English L.L., White D.G., Wagne D.D. High-level ciprofloxacin MICs develop rapidly in Campylobacter jejuni following treatment of chickens with sarafloxacin. In: American Society for Microbiology, 101st Annual Meeting, Orlando, Florida, ASM Press, Washington, D.C. (2001), p. 742 Abstract Z-20.

20. Unicomb L. E., Ferguson J., Stafford R. J.et al. Low-level fluoroquinolone resistance among Campylobacter jejuni isolates in Australia. Clin Infect Dis 2006; 42: 10: 1368—1374.

21. Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. 2012; ISSN 1600-2032: 80—83.

22. Payot S., Bolla J. M., Corcoran D. et al. Mechanisms of fluoroquinolone and macrolide resistance in Campylobacter spp. Microb Infect 2006; 8: 7: 1967—1971.

23. Olkkola S. Antimicrobial Resistance and Its Mechanisms among Campylobacter coli and Campylobacter upsaliensis with a special focus on streptomycin. Dissertationes Schola Doctoralis Scientiae Circumiectalis, Alimentariae, Biologicae. 2016.

24. Hannula M. Mechanisms and development of antimicrobial resistance in campylobacter with special reference to ciprofloxacin university of Helsinki. Faculty of Veterinary Medicine. 2010; 73: 1—73.

25. Qin S., Wang Y., Zhang Q., Deng F., Shen Z., Wu C. et al. Report of ribosomal RNA methylase gene erm(B) in multidrug resistant Campylobacter coli. Antimicrob Chemother 2014; 69: 964—968. http://dx.doi.org/10.1093/jac/dkt492/

26. Wang Y., Zhang M., Deng F., Shen Z., Wu C., Zhang J. et al. Emergence of Multidrug-Resistant Campylobacter Species Isolates with a Horizontally Acquired rRNA Methylase. Antimicrob Agents Chemother 2014; 58: 5405—5412.

27. Vacher S., Menard A., Bernard E., Santos A., Megraud F. Detection of mutations associated with macrolide resistance in thermophilic Campylobacter spp. by real-time PCR. Microb Drug Resist 2005; 11: 40—47.

28. Ефимочкина H.P., Стеценко В.В., Быкова КБ., Маркова Ю.М., Коля- нина А. С, Алешкина А.К., Шевелева С.А. Исследование фенотипической и генотипической экспрессии антибиотикорезистентности Campylobacter jejuni под влиянием стрессовых воздействий. Бюллетень экспериментальной биологии и медицины. — 2017. — Т. 164. — № 10. — С. 464—472. / Efimochkina N.R., Korotkevich YU. V, Stetsenko V.V., Pichugina T.V., Bykova L.B., Minaeva L.P., SHeveleva S.A. Antibiotikorezistentnost' shtammov Campylobacter jejuni, vydelennykh iz pishchevykh produktov. Voprosy pitaniya 2017; 1:18—28. [in Russian]

29. Laprade N., Cloutier M., Lapen D. R. et al. Detection of virulence, antibiotic resistance and toxin (VAT) genes in Campylobacter species using newly developed multiplex PCR assays. J Microbiol Methods 2016; 124: 41—47.

30. Sahin O., Shen Z., Zhang Q. Methods to study antimicrobial resistance in Campylobacter jejuni. Campylobacter jejuni. Humana Press, New York, NY. 2017; 29—42.

31. Gibreel A., Tracz D.M., Nonaka L., Ngo T.M., Connell S.R., Taylor D.E. Incidence of Antibiotic Resistance in Campylobacter jejuni Isolated in Alberta, Canada, from 1999 to 2002, with Special Reference to tet(O)- Mediated Tetracycline Resistance. Antimicrob Agents Chemother 2004; 48: 9: 3442—3450.

32. Zhang Q., Plummer P.J. Mechanisms of antibiotic resistance in Campylobacter. Campylobacter, Third Edition. Amer Soc Microbiol 2008; 263—276.