THE EFFECT OF SUBINHIBITORY CONCENTRATIONS OF ETHYLMETHYLHYDROXYPYRIDINE SUCCINATE ON BIOFILMS OF MICROORGANISMS

Vazhnichaya E. M., Baliuk O. Ye., Bobrova N. A., Boiko I. O.

MICROBIOLOGY

Scentific article

Biofilm microorganisms cause about 80% of chronic infections, leading to increased morbidity, increased hospital stays and enhanced health care costs. Biofilms can also grow on abiotic surfaces, including orthopedic prostheses, stents, and catheters. Antibiotics are not effective enough to treat biofilm infections, and antibiofilm agents are being sought among other classes of compounds, in particular antioxidants, including the well-known drug ethylmethylhydroxypyridine succinate (mexidol). The aim of the research was to study the effect of mexidol on the formation of biofilms by test strains of microorganisms. Clinical strains of bacteria (E. coli 311, P. aeruginosa 449, S. aureus 222) and fungi (C. albicans 1486) were used. The antimicrobial activity of mexidol was determined by serial dilutions in liquid media in the concentration range of 1.5-200 μg/ml. Determination of the microorganisms ability to form biofilm was performed according to the known O’Toole method. A degree of the biofilm formation intensity was determined as described by Stepanovic S. et al. The potential antibiofilm activity of mexidol was studied at concentrations of 5–200 μg/ml. Statistical processing of the results was performed using Newman-Keuls criterion by the software StatSoft Statistica 6.0. It was shown that for planktonic forms of E. coli, P. aeruginosa, S. aureus, and C. albicans, the minimum inhibitory concentration of mexidol is more 200 μg/ml. E. coli 311 and P. aeruginosa 449 show a strong ability to form biofilms, S. aureus 222 – the medium ability. C. albicans 1486 does not adhere to the abiotic surface and was no longer used. Mexidol enhances the biofilm production by E. coli 311, increasing the biomass of biofilms by 12–15%. The drug increases the biomass of P. aeruginosa biofilms by 33–110% against control, and this is most pronounced at the minimum concentration of the drug. Mexidol also stimulates the formation of S. aureus 222 biofilms by 2.1-2.7 times compared to the control. Therefore, under the action of the drug at subinhibitory concentrations, stimulation of the biofilm formation by gram-negative (E. coli 311, P. aeruginosa 449) and gram-positive bacteria (S. aureus 222) is observed. The identifiedability of mexidol to stimulate biofilm formation requires further research to assess the feasibility of its use in the complex therapy of purulent-inflammatory diseases.

ethylmethylhydroxypyridine succinate, mexidol, microorganisms, clinical strains, biofilm.

1. Kostakioti M, Hadjifrangiskou M, Hultgren SJ. Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med. 2013 Apr;3(4):a010306. DOI: 10.1101/cshperspect.a010306.
2. Kaplan JB. Antibiotic-induced biofilm formation. Int J Artif Organs. 2011 Sep;34(9):737-51. DOI: 10.5301/ijao.5000027.
3. Chimileski S, Franklin MJ, Papke RT. Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. BMC Biology. 2014 Aug;12:65. DOI: 10.1186/s12915-014-0065-5.
4. Magana M, Sereti C, Ioannidis A, Mitchell CA, Ball AR, Magiorkinis E, et al. Options and limitations in clinical investigation of bacterial biofilms. Clin Microbiol Rev. 2018 Jul;31(3):e00084-16. DOI: 10.1128/CMR.00084-16.
5. Yan J, Bassler BL. Surviving as a community: antibiotic tolerance and persistence in bacterial biofilms. Cell Host Microbe. 2019 Jul;26(1):15- 21. DOI: 10.1016/j.chom.2019.06.002.
6. Sharma D, Misba L, Khan AU. Antibiotics versus biofilm: an emerging battleground in microbial communities. Antimicrob Resist Infect Control . 2019 May 16;8:76. DOI: 10.1186/s13756-019-0533-3.
7. Roy R, Tiwari M, Donelli G, Virulence VT. Strategies for combating bacterial biofilms: a focus on anti-biofilm agents and their mechanisms of action. Virulence. 2018 Jan;9(1):522-54. DOI: 10.1080/21505594.2017. 1313372.
8. Hrynchuk NI, Vrynchanu NO, Bukhtiarova TA, Dudikova DM, Korotkyi YuV, Bondarenko LB. Antybioplivkova diia pokhidnoho adamantana shchodo Staphylococcus aureus. Mikrobiol. Z. 2021;83(1):58-67. DOI: 10.15407/microbiolj83.01.058. [in Ukrainian].
9. Francolini I, Piozzi A. Role of antioxidant molecules and polymers in prevention of bacterial growth and biofilm formation. Curr Med Chem. 2020;27(29):4882-904. DOI: 10.2174/0929867326666190409120409.
10. Dinicola S, De Grazia S, Carlomagno G, Pintucci JP. N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur Rev Med Pharmacol Sci. 2014 Oct;18(19):2942-8.
11. Memariani H, Memariani M, Ghasemian A. An overview on anti-biofilm properties of quercetin against bacterial pathogens. World J Microbiol Biotechnol. 2019 Sep;35(9):143. DOI: 10.1007/s11274-019-2719-5.
12. Voronina TA, Ivanova EA. Kombinirovannoe primenenie meksidola s izvestnyimi lekarstvennyimi sredstvami. Zhurnal nevrologii i psihiatrii. 2019;4:115-124. DOI: 10.17116/jnevro2019119041115. [in Russian].
13. Schulkin AV. Meksidol: sovremennyie aspektyi farmakokinetiki i farmakodinamiki. Farmateka. 2016;4(16):65-71. Dostupno: article/33771. [in Russian].
14. Semina SA, Sidorenko SV, Rezvan SP, Grudinina SA, Strachunskiy LS, Stetsyuk OU, et al. Opredelenie chuvstvitelnosti mikroorganizmov k antibakterialnyim preparatam (Metodicheskie ukazaniya MUK 4.2.1890-04). Klin mikrobiol antimikrob himioter. 2004;6(4):306-59. [in Russian].
15. Nekrasova LS, Svyta VM, Hlushkevych TH, Tomchuk VV, Zherebko NM, Pokas OV. Vyznachennia chutlyvosti mikroorhanizmiv do antybakterialnykh preparativ: Metodychni vkazivky MV 9.9.5-143-2007. Kyiv: MOZ Ukrainy; 2007. 73 s. [in Ukrainian].
16. O’Toole GA. Microtiter dish biofilm formation assay. J Vis Exp. 2011 Jan 30;(47):2437. DOI: 10.3791/2437.
17. Stepanovic S, Vukovic D, Hola V, Di Bonaventura G, Djukic S, Cirkovic I. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS. 2007 Aug;115(8):891-9. DOI: 10.1111/j.1600-0463.2007.apm_630.x.

«Bulletin of problems biology and medicine» Issue 1 (163), 2022 year, 203-207 pages, index UDK 579.22:615.28

10.29254/2077-4214-2022-1-163-203-207