Antimicrobial Resistance: A Risk Factor for the Biosafety System

Scientific relevance. In recent years, antimicrobial resistance in pathogenic microorganisms has become a global problem that threatens the health of humans and animals and poses a risk to the biosafety of Russia.

Aim. The study aimed to analyse the prevalence of antimicrobial resistance, consider the risks and medical consequences of this biological phenomenon, and suggest ways to optimise the use of existing antimicrobial agents and search for new ones.

Discussion. The emergence of antibiotic resistance in bacteria is a natural biological process; the selection of resistant microorganisms occurs constantly with the use of the entire spectrum of antimicrobial agents in healthcare, agriculture, and other fields. The World Health Organisation (WHO) monitors these processes using the Global Antimicrobial Resistance Surveillance System (GLASS). Russia has adopted the Strategy to prevent the spread of antimicrobial resistance in the Russian Federation to 2030. The country has established a regulatory framework that supports the operation of the national antimicrobial resistance prevention system. The strategy to prevent the spread of antimicrobial resistance is being implemented through making organisational arrangements and developing novel medicines with mechanisms of action based on an understanding of the molecular mechanisms of infection and resistance. This review considers the main approaches to designing exploratory studies and evaluating the antimicrobial activity of the innovative molecules obtained. The rapid development of synthetic biology increases the likelihood of creating synthetic biological pathogens with high virulence and resistance to antimicrobial agents, which might pose risks of artificial epidemics.

Conclusions. The antimicrobial resistance prevention system in Russia should be considered a strategically essential medical technology ensuring the biosafety of the country and the people.

1. Supotnitskiy MV. COVID-19: a difficult exam for humanity. Moscow: Russkaya panorama; 2021 (In Russ.).

2. Kolbin AS, Gomon YuM, Balykina YuE, Belousov DYu, Strizheletskiy VV, Ivanov IG. Socioeconomic and global burden of COVID-19. Good Clinical Practice. 2021;(1):24–34 (In Russ.). https://doi.org/10.37489/2588-0519-2021-1-24-34

3. Orekhov SN, Yavorsky AN. The coronavirus pandemic: biosafety risks at the therapeutic and laboratory levels. In: Sinyukov VN, Mokhov AA, eds. Law and countering the pandemic: opportunities and prospects: monograph. Moscow: Prospect; 2021. P. 416–33 (In Russ.).

4. Zaniboni D, Ceretti E, Gelatti U, Pezzotti M, Covolo L. Antibiotic resistance: is knowledge the only driver for awareness and appropriate use of antibiotics? Ann Ig. 2021;33(1):21–30. https://doi.org/10.7416/ai.2021.2405

5. Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, Laxminarayan R. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742–50. https://doi.org/10.1016/S1473-3099(14)70780-7

6. Kozlov RS, Golub AV. To stop the progress of antimicrobial resistance today means to give a chance of mankind surviving tomorrow. Clinical Microbiology and Antimicrobial Chemotherapy. 2019;21(4):310–15 (In Russ.). https://doi.org/10.36488/cmac.2019.4.310-315

7. Hanberger H, Diekema D, Fluit A, Jones R, Struelens M, Spencer R, Wolff M. Surveillance of antibiotic resistance in European ICUs. J Hosp Infect. 2001;48(3):161–76. https://doi.org/10.1053/jhin.2001.0987

8. Dolecek C, Shakoor S, Basnyat B, Okwor T, Sartorius B. Drug-resistant bacterial infections: We need urgent action and investment that focus on the weakest link. PLoS Biol. 2022;20(11):e3001903. https://doi.org/10.1371/journal.pbio.3001903

9. Pariente N; PLOS Biology Staff Editors. The antimicrobial resistance crisis needs action now. PLoS Biol. 2022;20(11):e3001918. https://doi.org/10.1371/journal.pbio.3001918

10. Aslam B, Wang W, Arshad MI, Khurshid M, Muzammil S, Rasool MH, et al. Antibiotic resistance: a rundown of a global crisis. Infect Drug Resist. 2018;11:1645–58. https://doi.org/10.2147/IDR.S173867

11. Davydov DS. The national strategy of the Russian Federation for preventing the spread of antimicrobial resistance: challenges and prospects of controlling one of the global biological threats of the 21st century. Biological Products. Prevention, Diagnosis, Treatment. 2018;18(1):50–6 (In Russ.). https://doi.org/10.30895/2221-996X-2018-18-1-50-56

12. Kisil OV, Gabrielyan NI, Maleev VV. Antibiotic resistance — what can be done? A review. Therapeutic Archive. 2023;95(1):90–5 (In Russ.). https://doi.org/10.26442/00403660.2023.01.202040

13. Kuzmenkov AYu, Vinogradova AG, Trushin IV, Edelstein MV, Avramenko AA, Dekhnich AV, Kozlov RS. AMRmap — antibiotic resistance surveillance system in Russia. Clinical Microbiology and Antimicrobial Chemotherapy. 2021;23(2):198– 204. https://doi.org/10.36488/cmac.2021.2.198-204

14. Mokhov AA. Antibacterial therapy in medicine and biological safety. In: Mokhov AA, Sushkova OV, eds. Legal basics of bioeconomics and biosafety: monograph. Moscow: Prospect; 2020. P. 171–7 (In Russ.).

15. Efimenko TA, Terekhova LP, Efremenkova OV. Current state the problem of antibiotic resistance of pathogens. Antibiotics and Chemotherapy. 2019;64(5–6):64–8 (In Russ.). EDN: GJTLZH

16. Hollis A., Ahmed Z. Preserving antibiotics, rationally. N Engl J Med. 2013:369(26):2474–6. https://doi.org/10.1056/nejmp1311479

17. Khare A. Achilles’ heel of antibiotic resistance. Nat Microbiol. 2021;6(11):1339–40. https://doi.org/10.1038/s41564-021-00985-x

18. Spivak ES, Cosgrove SE, Srinivasan A. Measuring appropriate antimicrobial use: attempts at opening the black box. Clin Infect Dis. 2016;63(12):1639–44. https://doi.org/10.1093/cid/ciw658

19. Munita JM, Arias CA. Mechanisms of antibiotic resistance. Microbiol Spectr. 2016;4(2):10.1128/microbiolspec.VMBF0016-2015. https://doi.org/10.1128/microbiolspec.VMBF-0016-2015

20. Reygaert WC. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol. 2018;4(3):482-501. https://doi.org/10.3934/microbiol.2018.3.482

21. Perry JA, Wright GD. The antibiotic resistance “mobilome”: searching for the link between environment and clinic. Front Microbiol. 2013;4:138. https://doi.org/10.3389/fmicb.2013.00138

22. Bennett P.M. Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria. Br J Pharmacol. 2009:153(Suppl. 1): S347–S357. https://doi.org/10.1038%2Fsj.bjp.0707607

23. Chen J, Quiles-Puchalt N, Chiang YN, Bacigalupe R, Fillol-Salom A, Juan Chee MS, et al. Genome hypermobility by lateral transduction. Science. 2018:362(6411):207–12. https://doi.org/10.1126/science.aat5867

24. Ringel PD, Hu D, Basler M. The role of type VI secretion system effectors in target cell lysis and subsequent horizontal gene transfer. Cell Rep. 2017:21(13):3927–40. https://doi.org/10.1016/j.celrep.2017.12.020

25. Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, Robinson TP, et al. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci USA. 2015;112(18):5649–54. https://doi.org/10.1073/pnas.1503141112

26. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. PT. 2015;40(4):277–83. PMID: 25859123

27. Zakharova OI, Liskova EA, Mikhaleva TV, Blokhin AA. Antibiotic resistance: evolutionary prerequisites, mechanisms, consequences. Agricultural Science Euro-North-East. 2018;64(3):13–21 (In Russ.). https://doi.org/10.30766/2072-9081.2018.64.3.13-21

28. Kovalchuk SN, Fedorova LS, Ilina EN. Molecular mechanisms of microbial resistance to disinfectants. Antibiotics and Chemotherapy. 2023;68(1–2):45–56 (In Russ.). https://doi.org/10.37489/0235-2990-2023-68-1-2-45-56

29. Mokhov AA. Strategically significant medical technologies: legal aspect. State and Law. 2020;(11):106–14 (In Russ.). https://doi.org/10.31857/S102694520012528-1

30. Supotnitskiy MV. Biological warfare. Introduction to the epidemiology of artificial epidemic processes and biological lesions: monograph. Moscow: Russkaya panorama; 2013 (In Russ.).

31. Jansen HJ, Breeveld FJ, Stijnis C, Grobusch MP. Biological warfare, bioterrorism, and biocrime. Clin Microbiol Infect. 2014;20(6):488–96. https://doi.org/10.1111/1469-0691.12699

32. Kirillov IA. The world has entered the era of synthetic biological weapons. Journal of NBC Protection Corps. 2022;6(4):303 (In Russ.). EDN: WBRXBK

33. Miethke M, Pieroni M, Weber T, Broenstrup M, Hammann P, Halby L, et al. Towards the sustainable discovery and development of new antibiotics. Nat Rev Chem. 2021;5(10):726–49. https://doi.org/10.1038/s41570-021-00313-1

34. Supotnitskiy МV. Mechanisms of antibiotics resistance in bacteria. Biological Products. Prevention, Diagnosis, Treatment. 2011;(2):4–13 (In Russ.). EDN: RDTUFZ

35. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, et al. A new antibiotic kills pathogens without detectable resistance. Nature. 2015;517(7535):455–9. https://doi.org/10.1038/nature14098

36. Mitcheltree MJ, Pisipati A, Syroegin EA, Silvestre KJ, Klepacki D, Mason JD, et al. A synthetic antibiotic class overcoming bacterial multidrug resistance. Nature. 2021;599(7885):507–12. https://doi.org/10.1038/s41586-021-04045-6

37. Wang Z, Koirala B, Hernandez Y, Zimmerman M, Brady SF, et al. Bioinformatic prospecting and synthesis of a bifunctional lipopeptide antibiotic that evades resistance. Science. 2022;376(6596):991–6. https://doi.org/10.1126/science.abn4213

38. Ottonello A, Wyllie JA, Yahiaoui O, Sun S, Koelln RA, Homer JA, et al. Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria. Proc Natl Acad Sci USA. 2023;120(15):e2208737120. https://doi.org/10.1073/pnas.2208737120

39. Tsarenko SV, Zigangirova NA, Soloveva AV, Bondareva NE, Koroleva EA, Sheremet AB, et al. A novel antivirulent compound fluorothiazinone inhibits Klebsiella pneumoniae biofilm in vitro and suppresses model pneumonia. J Antibiot (Tokyo). 2023;76:397–405. https://doi.org/10.1038/s41429-023-00621-2

40. Sadykova VS, Gavryushina IA, Kuvarina AE, Markelova NN, Sedykh NG, Georgieva ML, et al. Antimicrobic activity of the lipopeptide emericellipsin A isolated from Emericellopsis alkalina against biofilm-forming bacteria. Appl Biochem Microbiol. 2020;56:292–7. https://doi.org/10.1134/S0003683820030102

41. Tyurin AP, Alferova VA, Paramonov AS, Shuvalov MV, Kudryakova GK, Rogozhin EA, et al. Gausemycins A,B: cyclic lipoglycopeptides from Streptomyces sp. Angew Chem Int Ed Engl. 2021;60(34):18694–703. https://doi.org/10.1002/anie.202104528