Obstetrics and GynecologyObstetrics and GynecologyАкушерство и гинекология0300-90922412-5679Bionika Media24797210.18565/aig.2017.3.108-14ArticlesСтатьиResearch ArticleMetabolites of the normal vaginal microflora increase the activity of antibioticsПотенцирование активности антибиотиков метаболитами нормальной вагинальной микрофлорыSgibnevAndrey ViktorovichСгибневАндрей Викторович

doctor of biology, associate professor, leading researcher, Laboratory for the study of the mechanisms of formation microbiocenoses of humans

д.б.н., доцент, в.н.с. лаборатории по изучению механизмов формирования микробиоценозов человека

andrej-sgibnev@yandex.ruKremlevaElena AleksandrovnaКремлеваЕлена Александровна

MD, leading researcher, Laboratory for the study of the mechanisms of formation microbiocenoses of humans; Associate Professor, Department of Obstetrics and Gynecology

д.м.н., в.н.с. лаборатории по изучению механизмов формирования микробиоценозов человека; доцент кафедры акушерства и гинекологии

kremlena1@mail.ruInstitute of Cellular and Intracellular Symbiosis, Ural Branch of RASФГБУН Институт клеточного и внутриклеточного симбиоза УрО РАНOrenburg State Medical UniversityГБОУ ВПО Оренбургский государственный медицинский университет Минздрава России150320173NO3 (2017)№3 (2017)10811418022023Copyright ©; 2017, Bionika MediaCopyright ©; 2017, ООО «Бионика Медиа»2017Bionika MediaООО «Бионика Медиа»https://journals.eco-vector.com/0300-9092/article/view/247972

Objective. Investigation of the influence of metabolites from the lactobacilli isolated from healthy women and LCR35probiotic strain on sensitivity to antibiotics. Subject and methods. We studied the effects of H2O2, lactate, and surfactants obtained from 24 vaginal Lactobacillus spp. and metabolites from L CR35 on sensitivity to antibiotics of 172 strains of opportunistic bacteria. Results. H2O2 and surfactants but no lactic acid were more effective for increasing the sensitivity of bacteria to antibiotics. Strain LCR35 increased sensitivity to antibiotics of all test strains, to a greater extent - G. vaginalis, E. coli and Klebsiella spp. Conclusion. The phenomenon of potentiation of activity of antibiotic by metabolites from vaginal lactobacilli and LCR35 probiotic strain was detected. For effective treatment of inflammatory diseases by antibiotics should take into account the status of the normal microflora, and if necessary, compensate deficit by probiotic strains able to produce “assistants antibiotics”.

Цель исследования. Изучение влияния метаболитов лактобацилл, выделенных от здоровых женщин, и пробиотического штамма LCR35 на чувствительность к антибиотикам. Материал и методы. Изучали влияние Н2О2, лактата и сурфактантов, полученных от 24 вагинальных Lactobacillus spp., и метаболитов LCR35 на чувствительность к антибиотикам 172 штаммов условно-патогенных бактерий. Результаты. Наиболее эффективными в повышении чувствительности бактерий к антибиотикам были пероксид водорода и сурфактанты, но не молочная кислота. LCR35 повышала чувствительность к антибиотикам всех тест-штаммов, в большей мере - G. vaginalis, E.coli и Klebsiella spp. Заключение. Обнаружен феномен потенцирования действия антибиотиков метаболитами вагинальных лактобацилл и пробиотического штамма LCR35. Для эффективной терапии воспалительных заболеваний необходимо учитывать состояние нормальной микрофлоры на момент применения антибиотиков, при необходимости восполняя ее дефицит пробиотическими штаммами, способными к продукции «ассистентов антибиотиков».

antibiotic resistancehydrogen peroxidelactic acidlactobacillusprobioticssurface-active agentsантибиотикорезистентностьлактобациллымолочная кислотапероксид водородаповерхностно-активные веществаWomen and health: today’s evidence, tomorrow’s agenda. Geneva: World Health Organization; 2009. Available at: http://apps.who.int/iris/bitstre am/10665/44168/1/9789241563857_eng.pdДодова Е.Г., Аполихина И.А., Горбунова Е.А., Бородина Е.А. Комплексное лечение воспалительных заболеваний нижних отделов генитального тракта у женщин. Акушерство и гинекология. 2015; 6: 129-35. [Kurchakova T.A., Veresova A.A., Tyutyunnik V.L., Kan N.E. Current approaches to treating papillomavirus infection. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2015; (6): 129-35. (in Russian)]Levy S.B., Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nat. Med. 2004; 10(12, Suppl.): S122-9.Bancroft E.A. Antimicrobial resistance: it’s not just for hospitals. JAMA. 2007; 298(15):1803-4.Roca I., Akova M., Baquero F., Carlet J., Cavaleri M., Coenen S. et al. The global threat of antimicrobial resistance: science for intervention. New Microbes New Infect. 2015; 6: 22-9.Worthington R.J., Melander C. Combination approaches to combat multidrug-resistant bacteria. Trends Biotechnol. 2013; 31(3):177-84.Viens A.M., Littmann J. Is Antimicrobial resistance a slowly emerging disaster? Public Health Ethics. 2015; 8(3): 255-65.Mandal S.M., Roy A., Ghosh A.K., Hazra T.K., Basak A., Franco O.L. Challenges and future prospects of antibiotic therapy: from peptides to phages utilization. Front. Pharmacol. 2014; 5: 105.Mishra R.K., Segal E., Lipovsky A., Natan M., Banin E., Gedanken A. New life for an old antibiotic. ACS Appl. Mater. Interfaces. 2015; 7(13): 7324-33.Macklaim J.M., Clemente J.C., Knight R., Gloor G.B., Reid G. Changes in vaginal microbiota following antimicrobial and probiotic therapy. Microb. Ecol. Health Dis. 2015; 26: 27799.Bodean O., Munteanu O., Cirstoiu C., Secara D., Cirstoiu M. Probiotics - a helpful additional therapy for bacterial vaginosis. J. Med. Life. 2013; 6(4): 434-6.Sgibnev A., Kremleva E. Vaginal protection by H2O2-producing lactobacilli. Jundishapur J. Microbiol. 2015; 8(10): e22913.Aldunate M., Srbinovski D., Hearps A.C., Latham C.F., Ramsland P.A., Gugasyan R. et al. Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis. Front. Physiol. 2015; 6: 164.O’Hanlon D.E., Moench T.R., Cone R.A. Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PloS One. 2013; 8(11): e80074.Sambanthamoorthy K., Feng X., Patel R., Patel S., Paranavitana C. Antimicrobial and antibiofilm potential of biosurfactants isolated from lactobacilli against multi-drug-resistant pathogens. BMC Microbiology. 2014; 14: 197.Shokouhfard M., Kermanshahi R.K., Shahandashti R.V., Feizabadi M.M., Teimourian S. The inhibitory effect of a Lactobacillus acidophilus derived biosurfactant on biofilm producer Serratia marcescens. Iran. J. Basic Med. Sci. 2015; 18(10): 1001-7.Whitman W.B., Goodfellow M., Kämpfer P., Busse H.-J., Trujillo M.E., Ludwig W. Bergey’s manual of systematic bacteriology. 2nd ed. vol. 5(Pt A and B). New York: Springer-Verlag; 2012.Willumsen P.A., Karlson U. Screening of bacteria, isolated from PAH-contaminated soils, for production of biosurfactants and bioemulsifiers. Biodegradation. 1997; 7(5): 415-23.CLSI. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically : approved standard. 10th ed. CLSI document M07-A10. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.Савичева А.М., Рыбина Е.В. Исследование in vitro роста, размножения, антибиотикорезистентности, конкурентных взаимоотношений штамма Lactobacillus casei rhamnosus. Акушерство и гинекология. 2014; 7: 79-83. [Savicheva A.M., Rybina E.V. In vitro study of the growth, reproduction, antibiotic resistance, and competitive relationships of a Lactobacillus casei rhamnosus strain. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2014; (7): 79-83. (in Russian)]Borges S., Silva J., Teixeira P. The role of lactobacilli and probiotics in maintaining vaginal health. Arch. Gynecol. Obstet. 2014; 289(3): 479-89.Dover S.E., Aroutcheva A.A., Faro S., Chikindas M.L. Natural antimicrobials and their role in vaginal health: a short review. Int. J. Probiotics Prebiotics. 2008; 3(4): 219-30.Albesa I., Becerra M.C., Battán P.C., Páez P.L. Oxidative stress involved in the antibacterial action of different antibiotics. Biochem. Biophys. Res. Commun. 2004; 317(2): 605-9.Dwyer D.J., Belenky P.A., Yang J.H., MacDonald I.C., Martell J.D., Takahashi N. et al. Antibiotics induce redox-related physiological alterations as part of their lethality. Proc. Natl. Acad. Sci. USA. 2014; 111(20): E2100-9.Kohanski M.A., Dwyer D.J., Hayete B., Lawrence C.A., Collins J.J. A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007; 130(5): 797-810.Grant S.S., Hung D.T. Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response. Virulence. 2013; 4(4): 273-83.Bernier S.P., Létoffé S., Delepierre M., Ghigo J.M. Biogenic ammonia modifies antibiotic resistance at a distance in physically separated bacteria. Mol. Microbiol. 2011; 81(3): 705-16.