Actual problems in dentistry Actual problems in dentistry Проблемы стоматологии 2077-7566 2412-9461 81394 10.18481/2077-7566-2024-20-1-45-51 ЛЕКЦИИ / ЛИТЕРАТУРНЫЕ ОБЗОРЫ LITERATURE REVIEW ЛЕКЦИИ / ЛИТЕРАТУРНЫЕ ОБЗОРЫ ROLE OF MOLECULAR GENETIC RESEARCH METHODS IN THE ETIOPATHOGENESIS OF OSTEOMYELITIS OF THE JAWS РОЛЬ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ МЕТОДОВ ИССЛЕДОВАНИЙ В ЭТИОПАТОГЕНЕЗЕ ОСТЕОМИЕЛИТА ЧЕЛЮСТЕЙ https://orcid.org/0000-0002-0855-6578 Файзуллина Гузель Ахмятовна Fayzullina Guzel Ahmyatovna flamingo004@yandex.ru

кандидат медицинских наук;

candidate of medical sciences;

 https://orcid.org/0000-0002-8956-0690 Мирсаева Фания Зартдиновна Mirsaeva Faniya Zartdinovna Faniya-Mirsaeva@mail.ru

доктор медицинских наук;

doctor of medical sciences;

 Башкирский государственный медицинский университет Уфа Россия Bashkir State Medical University Ufa Russian Federation Башкирский государственный медицинский университет Bashkirian State Medical University 02 05 2024 02 05 2024 20 1 45 51 06 04 2024 https://dental-press.ru/en/nauka/article/81394/view

Предмет исследования — значение молекулярно-генетических методов исследования в изучении этиопатогенеза остеомиелита челюстей. Цель работы — представить исследователям, врачам-стоматологам-хирургам, челюстно-лицевым хирургам актуальную информацию по возможностям молекулярно-генетических изысканий в вопросах выявления бактериальных патогенов при остеомиелите челюстей, а также отразить генетические маркеры факторов патогенности ряда основных возбудителей заболевания. Методология. Использованы международные научные базы данных PubMed, ScienceDirect, Scopus, Cochrane Collaboration, Elsevier, а также электронные каталоги eLIBRARY.RU и КиберЛенинка. Результаты. Обзор публикаций продемонстрировал, что S. aureus и S. Epidermidis доминируют в этиологическом спектре возбудителей инфекционных процессов костной ткани. Участие данных микроорганизмов определяется целым спектром факторов патогенности. В патогенезе остеомиелита и прогрессировании заболевания главную роль играют токсины и гены лейкоцидин Пантона–Валентайна (PVL). Показано, что патогенные бактерии Porphyromonas gingivalis и Aggregatibacter actinomycetemcomitans способны индуцировать дифференцированную продукцию цитокинов. Наибольшее внимание привлекает Е. faecium, который проявляет мультирезистентность к широкому спектру антибиотиков. Доля инфекций, опосредованных S. epidermidis, S. Saprophyticus составляет, в среднем, порядка 25% случаев. Доля представителей грамотрицательной флоры Escherichia, Klebsiella, Enterobacter, Citrobacter, Proteus, Providencia, Serratia достигает 23% случаев. Патогенные нозокомиальные штаммы P. aeruginosa также вовлечены в формирование хронического воспаления при остеомиелите. По результатам опубликованных исследований, более трети случаев хронического остеомиелита опосредовано микробными ассоциациями, в составе которых доминируют S. aureus, S. epidermidis и реже E. faecalis. Выводы. Применение ПЦР-анализа для идентификации возбудителей остеомиелита и амплификация генов с использованием специфичных праймеров имеет огромное преимущество перед рутинными микробиологическими тестами, являясь информативным методом исследования факторов патогенности основных возбудителей. Высокая значимость молекулярно-генетических методов в изучении этиопатогенеза остеомиелита челюстей требует их широкого применения в клинике хирургической стоматологии и челюстно-лицевой хирургии для успешного решения сложных задач по реабилитации пациентов с данным заболеванием.

The subject of the study is the importance of molecular genetic research methods in the study of the etiopathogenesis of osteomyelitis of the jaws. The purpose of the work is to provide up-to-date information to researchers, dental surgeons, and maxillofacial surgeons on the possibilities of molecular genetic research in identifying bacterial pathogens in osteomyelitis of the jaws, as well as to reflect genetic markers of pathogenicity factors for a number of the main causative agents of the disease. Methodology. International scientific databases PubMed, ScienceDirect, Scopus, Cochrane Collaboration, Elsevier, as well as electronic catalogs eLIBRARY.RU and CyberLeninka.ru were used. Results. A review of publications demonstrated that S. aureus and S. Epidermidis dominate the etiological spectrum of causative agents of bone tissue infections. The participation of these microorganisms is determined by a whole range of pathogenicity factors. Toxins and Panton-Valentine leukocidin (PVL) genes play a major role in the pathogenesis of osteomyelitis and disease progression. It has been shown that the pathogenic bacteria Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are capable of inducing differentiated production of cytokines. The most attention has been attracted to E. faecium, which exhibits multidrug resistance to a wide range of antibiotics. The proportion of infections mediated by S. epidermidis and S. Saprophyticus is, on average, about 25% of cases. The proportion of representatives of gram-negative flora Escherichia, Klebsiella, Enterobacter, Citrobacter, Proteus, Providencia, Serratia reaches 23% of cases. Pathogenic nosocomial strains of P. aeruginosa are also involved in the formation of chronic inflammation in osteomyelitis. According to the results of published studies, more than a third of cases of chronic osteomyelitis are mediated by microbial associations, which are dominated by S. aureus, S. epidermidis and, less commonly, E. faecalis. Conclusions. The use of PCR analysis to identify the causative agents of osteomyelitis and gene amplification using specific primers has a huge advantage over routine microbiological tests, being an informative method for studying the pathogenicity factors of the main pathogens. The high importance of molecular genetic methods in the study of the etiopathogenesis of osteomyelitis of the jaws requires their widespread use in the clinic of surgical dentistry and maxillofacial surgery to successfully solve complex problems in the rehabilitation of patients with this disease.

 обзор литературы остеомиелит челюсти ПЦР молекулярно-генетические методы исследования генетические маркеры возбудителей остеомиелита literature review osteomyelitis of the jaw PCR molecular genetic research methods genetic markers of osteomyelitis pathogens

Spyropoulou V., Dhouib Chargui A., Merlini L., Samara E., Valaikaite R., Kampouroglou G. et al. Primary subacute hematogenous osteomyelitis in children: a clearer bacteriological etiology // J Child Orthop. – 2016;10(3):241-246. https://doi.org/10.1007/s11832-016-0739-3 Spyropoulou V., Dhouib Chargui A., Merlini L., Samara E., Valaikaite R., Kampouroglou G. et al. Primary subacute hematogenous osteomyelitis in children: a clearer bacteriological etiology // J Child Orthop. – 2016;10(3):241-246. https://doi.org/10.1007/s11832-016-0739-3 Nishitani K., Sutipornpalangkul W., de Mesy Bentley K.L., Varrone J.J., Bello-Irizarry S.N., Ito H. et al. Quantifying the natural history of biofilm formation in vivo during the establishment of chronic implant-associated Staphylococcus aureus osteomyelitis in mice to identify critical pathogen and host factors // J Orthop Res. – 2015;33(9):1311-1319. https://doi.org/10.1002/jor.22907 Nishitani K., Sutipornpalangkul W., de Mesy Bentley K.L., Varrone J.J., Bello-Irizarry S.N., Ito H. et al. Quantifying the natural history of biofilm formation in vivo during the establishment of chronic implant-associated Staphylococcus aureus osteomyelitis in mice to identify critical pathogen and host factors // J Orthop Res. – 2015;33(9):1311-1319. https://doi.org/10.1002/jor.22907 Mariani B.D., Martin D.S., Chen A.F., Yagi H., Lin S.S., Tuan R.S. Polymerase Chain Reaction molecular diagnostic technology for monitoring chronic osteomyelitis // J Exp Orthop. – 2014;1(1):9. https://doi.org/10.1186/s40634-014-0009-6 Mariani B.D., Martin D.S., Chen A.F., Yagi H., Lin S.S., Tuan R.S. Polymerase Chain Reaction molecular diagnostic technology for monitoring chronic osteomyelitis // J Exp Orthop. – 2014;1(1):9. https://doi.org/10.1186/s40634-014-0009-6 Ferroni A., Al Khoury H., Dana C., Quesne G., Berche P., Glorion C. et al. Prospective survey of acute osteoarticular infections in a French paediatric orthopedic surgery unit // Clin Microbiol Infect. – 2013;19(9):822-828. https://doi.org/10.1111/clm.12031 Ferroni A., Al Khoury H., Dana C., Quesne G., Berche P., Glorion C. et al. Prospective survey of acute osteoarticular infections in a French paediatric orthopedic surgery unit // Clin Microbiol Infect. – 2013;19(9):822-828. https://doi.org/10.1111/clm.12031 Qian J., Huang D., Fang M. A portable CRISPR Cas12a based lateral flow platform for sensitive detection of Staphylococcus aureus with double insurance // Food Control. – 2022;132:108485. https://doi.org/10.1016/j.foodcont.2021.108485 Qian J., Huang D., Fang M. A portable CRISPR Cas12a based lateral flow platform for sensitive detection of Staphylococcus aureus with double insurance // Food Control. – 2022;132:108485. https://doi.org/10.1016/j.foodcont.2021.108485 Shibata S., Tanizaki R., Watanabe K., Makabe K., Shoda N., Kutsuna S. et al. Escherichia coli Vertebral Osteomyelitis Diagnosed According to Broad-range 16S rRNA Gene Polymerase Chain Reaction (PCR) // Intern Med. – 2015;54(24):3237-3240. https://doi.org/10.2169/internalmedicine.54.5066 Shibata S., Tanizaki R., Watanabe K., Makabe K., Shoda N., Kutsuna S. et al. Escherichia coli Vertebral Osteomyelitis Diagnosed According to Broad-range 16S rRNA Gene Polymerase Chain Reaction (PCR) // Intern Med. – 2015;54(24):3237-3240. https://doi.org/10.2169/internalmedicine.54.5066 Гончаров А.Е., Зуева Л.П., Колоджиева В.В. Способ определения генотипов золотистого стафилококка. Патент РФ № 2526497 С2.2014. [A.E. Goncharov, L.P. Zueva, V.V. Kolodzhieva. Method for determination of Staphylococcus aureus genotypes. Patent RF № 2526497 S2. 2014. (In Russ.)]. https://www.elibrary.ru/download/elibrary_37803418_80472848.pdf Goncharov A.E., Zueva L.P., Kolodzhieva V.V. Sposob opredeleniya genotipov zolotistogo stafilokokka. Patent RF № 2526497 S2.2014. [A.E. Goncharov, L.P. Zueva, V.V. Kolodzhieva. Method for determination of Staphylococcus aureus genotypes. Patent RF № 2526497 S2. 2014. (In Russ.)]. https://www.elibrary.ru/download/elibrary_37803418_80472848.pdf Szafranska A.K., Oxley A.P., Chaves-Moreno D., Horst S.A., Roßlenbroich S., Peters G. et al. High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis // mBio. – 2014;5(6):e01775-e017714. https://doi.org/10.1128/mBio.01775-14 Szafranska A.K., Oxley A.P., Chaves-Moreno D., Horst S.A., Roßlenbroich S., Peters G. et al. High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis // mBio. – 2014;5(6):e01775-e017714. https://doi.org/10.1128/mBio.01775-14 Jarraud S., Mougel C., Thioulouse J., Lina G., Meugnier H., Forey F. et al. Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease // Infect Immun. – 2002;70(2):631-641. https://doi.org/10.1128/IAI.70.2.631-641.2002 Jarraud S., Mougel C., Thioulouse J., Lina G., Meugnier H., Forey F. et al. Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease // Infect Immun. – 2002;70(2):631-641. https://doi.org/10.1128/IAI.70.2.631-641.2002 Beenken K.E., Mrak L.N., Griffin L.M., Zielinska A.K., Shaw L.N., Rice K.C. et al. Epistatic relationships between sarA and agr in Staphylococcus aureus biofilm formation // PLoS One. – 2010;5(5):e10790. https://doi.org/10.1371/journal.pone.0010790 Beenken K.E., Mrak L.N., Griffin L.M., Zielinska A.K., Shaw L.N., Rice K.C. et al. Epistatic relationships between sarA and agr in Staphylococcus aureus biofilm formation // PLoS One. – 2010;5(5):e10790. https://doi.org/10.1371/journal.pone.0010790 Tristan A., Ying L., Bes M., Etienne J., Vandenesch F., Lina G. Use of multiplex PCR to identify Staphylococcus aureus adhesins involved in human hematogenous infections // J Clin Microbiol. – 2003;41(9):4465-4467. https://doi.org/10.1128/JCM.41.9.4465-4467.2003 Tristan A., Ying L., Bes M., Etienne J., Vandenesch F., Lina G. Use of multiplex PCR to identify Staphylococcus aureus adhesins involved in human hematogenous infections // J Clin Microbiol. – 2003;41(9):4465-4467. https://doi.org/10.1128/JCM.41.9.4465-4467.2003 Johansson A., Flock J.I., Svensson O. Collagen and fibronectin binding in experimental staphylococcal osteomyelitis // Clin Orthop Relat Res. – 2001;(382):241-246. https://doi.org/10.1097/00003086-200101000-00032 Johansson A., Flock J.I., Svensson O. Collagen and fibronectin binding in experimental staphylococcal osteomyelitis // Clin Orthop Relat Res. – 2001;(382):241-246. https://doi.org/10.1097/00003086-200101000-00032 Que Y.A., François P., Haefliger J.A., Entenza J.M., Vaudaux P., Moreillon P. Reassessing the role of Staphylococcus aureus clumping factor and fibronectin-binding protein by expression in Lactococcus lactis // Infect Immun. – 2001;69(10):6296-6302. https://doi.org/10.1128/IAI.69.10.6296-6302.2001 Que Y.A., François P., Haefliger J.A., Entenza J.M., Vaudaux P., Moreillon P. Reassessing the role of Staphylococcus aureus clumping factor and fibronectin-binding protein by expression in Lactococcus lactis // Infect Immun. – 2001;69(10):6296-6302. https://doi.org/10.1128/IAI.69.10.6296-6302.2001 Wiśniewska K., Piórkowska A., Kasprzyk J., Bronk M., Świeć K. Clonal distribution of bone sialoprotein-binding protein gene among Staphylococcus aureus isolates associated with bloodstream infections // Folia Microbiol (Praha). – 2014;59(6):465-471. https://doi.org/10.1007/s12223-014-0321-7 Wiśniewska K., Piórkowska A., Kasprzyk J., Bronk M., Świeć K. Clonal distribution of bone sialoprotein-binding protein gene among Staphylococcus aureus isolates associated with bloodstream infections // Folia Microbiol (Praha). – 2014;59(6):465-471. https://doi.org/10.1007/s12223-014-0321-7 Wann E.R., Gurusiddappa S., Hook M. The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aureus is a bifunctional protein that also binds to fibrinogen // J Biol Chem. – 2000;275(18):13863-13871. https://doi.org/10.1074/jbc.275.18.13863 Wann E.R., Gurusiddappa S., Hook M. The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aureus is a bifunctional protein that also binds to fibrinogen // J Biol Chem. – 2000;275(18):13863-13871. https://doi.org/10.1074/jbc.275.18.13863 Vandenesch F., Naimi T., Enright M.C., Lina G., Nimmo G.R., Heffernan H. et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence // Emerg Infect Dis. – 2003;9(8):978-984. https://doi.org/10.3201/eid0908.030089 Vandenesch F., Naimi T., Enright M.C., Lina G., Nimmo G.R., Heffernan H. et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence // Emerg Infect Dis. – 2003;9(8):978-984. https://doi.org/10.3201/eid0908.030089 Storz G., Vogel J., Wassarman K.M. Regulation by small RNAs in bacteria: expanding frontiers // Mol Cell. – 2011;43(6):880-891. https://doi.org/10.1016/j.molcel.2011.08.022 Storz G., Vogel J., Wassarman K.M. Regulation by small RNAs in bacteria: expanding frontiers // Mol Cell. – 2011;43(6):880-891. https://doi.org/10.1016/j.molcel.2011.08.022 Palka-Santini M., Pützfeld S., Cleven B.E., Krönke M., Krut O. Rapid identification, virulence analysis and resistance profiling of Staphylococcus aureus by gene segment-based DNA microarrays: application to blood culture post-processing // J Microbiol Methods. – 2007;68(3):468-477. https://doi.org/10.1016/j.mimet.2006.10.004 Palka-Santini M., Pützfeld S., Cleven B.E., Krönke M., Krut O. Rapid identification, virulence analysis and resistance profiling of Staphylococcus aureus by gene segment-based DNA microarrays: application to blood culture post-processing // J Microbiol Methods. – 2007;68(3):468-477. https://doi.org/10.1016/j.mimet.2006.10.004 Duman Y., Sevimli R. Investigation of the presence of pantone-valentine leukocidin in Staphylococcus aureus strains isolated from orthopedic surgical site infections // Mikrobiyol Bul. – 2018;52(4):340-347. https://doi.org/10.5578/mb.67328 Duman Y., Sevimli R. Investigation of the presence of pantone-valentine leukocidin in Staphylococcus aureus strains isolated from orthopedic surgical site infections // Mikrobiyol Bul. – 2018;52(4):340-347. https://doi.org/10.5578/mb.67328 Dubrac S., Msadek T. Identification of genes controlled by the essential YycG/YycF two-component system of Staphylococcus aureus // J Bacteriol. – 2004;186(4):1175-1181. https://doi.org/10.1128/JB.186.4.1175-1181.2004 Dubrac S., Msadek T. Identification of genes controlled by the essential YycG/YycF two-component system of Staphylococcus aureus // J Bacteriol. – 2004;186(4):1175-1181. https://doi.org/10.1128/JB.186.4.1175-1181.2004 Zhu X., Zhang K., Lu K., Shi T., Shen S., Chen X. et al. Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis // Ann Transl Med. – 2019;7(8):170. https://doi.org/10.21037/atm.2019.03.40 Zhu X., Zhang K., Lu K., Shi T., Shen S., Chen X. et al. Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis // Ann Transl Med. – 2019;7(8):170. https://doi.org/10.21037/atm.2019.03.40 Бухарин О.В., Валышева И.В., Карташова О.Л., Сычева М.В. Характеристика вирулентного потенциала клинических изолятов энтерококков. Журнал микробиологии. 2013;3:12-18. [O.V. Buharin, I.V. Valysheva, O.L. Kartashova, M.V. Sycheva. Characterization of the virulent potential of clinical isolates of enterococci. Journal of Microbiology. 2013;(3):12-18. (In Russ.)]. https://www.elibrary.ru/item.asp?id=23140970 Buharin O.V., Valysheva I.V., Kartashova O.L., Sycheva M.V. Harakteristika virulentnogo potenciala klinicheskih izolyatov enterokokkov. Zhurnal mikrobiologii. 2013;3:12-18. [O.V. Buharin, I.V. Valysheva, O.L. Kartashova, M.V. Sycheva. Characterization of the virulent potential of clinical isolates of enterococci. Journal of Microbiology. 2013;(3):12-18. (In Russ.)]. https://www.elibrary.ru/item.asp?id=23140970 Кузнецова М.В., Павлова Ю.А., Карпунина Т.И., Демаков В.А. Опыт использования методов молекулярной генетики при идентификации клинических штаммов Pseudomonas aerugenosa. Клиническая лабораторная диагностика. 2013;3:34-37. [M.V. Kuznecova, Ju.A. Pavlova, T.I. Karpunina, V.A. Demakov. Experience of using molecular genetics methods in the identification of clinical strains of Pseudomonas aerugenosa. Clinical laboratory diagnostics. 2013;(3):34-37. (In Russ.)]. https://www.elibrary.ru/item.asp?id=18923096 Kuznecova M.V., Pavlova Yu.A., Karpunina T.I., Demakov V.A. Opyt ispol'zovaniya metodov molekulyarnoy genetiki pri identifikacii klinicheskih shtammov Pseudomonas aerugenosa. Klinicheskaya laboratornaya diagnostika. 2013;3:34-37. [M.V. Kuznecova, Ju.A. Pavlova, T.I. Karpunina, V.A. Demakov. Experience of using molecular genetics methods in the identification of clinical strains of Pseudomonas aerugenosa. Clinical laboratory diagnostics. 2013;(3):34-37. (In Russ.)]. https://www.elibrary.ru/item.asp?id=18923096 Hadi Saleh T., Hashim S., Abdulrazaq Al-Obaidi R.A., Laftaah Al-Rubaii B.A. A biological study of chitinase produced by clinical isolates of pseudomonas aeruginosa and detection of chia responsible gene // Int J Res Pharm Sci. – 2020;11(2):1539-1544. htpps://doi.org/10.26452/ijrps.v11i2.2030 Hadi Saleh T., Hashim S., Abdulrazaq Al-Obaidi R.A., Laftaah Al-Rubaii B.A. A biological study of chitinase produced by clinical isolates of pseudomonas aeruginosa and detection of chia responsible gene // Int J Res Pharm Sci. – 2020;11(2):1539-1544. htpps://doi.org/10.26452/ijrps.v11i2.2030 Tang Y., Ali Z., Jin G. Detection methods for: Pseudomonas aeruginosa: History and future perspective // RSC Advances. – 2017; 82(7): 51789-51800. htpps://doi.org/10.1039/c7ra09064a Tang Y., Ali Z., Jin G. Detection methods for: Pseudomonas aeruginosa: History and future perspective // RSC Advances. – 2017; 82(7): 51789-51800. htpps://doi.org/10.1039/c7ra09064a De Vos D., Lim A. Jr., Pirnay J.P., Struelens M., Vandenvelde C., Duinslaeger L. et al. Direct detection and identification of Pseudomonas aeruginosa in clinical samples such as skin biopsy specimens and expectorations by multiplex PCR based on two outer membrane lipoprotein genes, oprI and oprL // J Clin Microbiol. – 1997;35(6):1295-1299. htpps://doi.org/10.1128/jcm.35.6.1295-1299.1997 De Vos D., Lim A. Jr., Pirnay J.P., Struelens M., Vandenvelde C., Duinslaeger L. et al. Direct detection and identification of Pseudomonas aeruginosa in clinical samples such as skin biopsy specimens and expectorations by multiplex PCR based on two outer membrane lipoprotein genes, oprI and oprL // J Clin Microbiol. – 1997;35(6):1295-1299. htpps://doi.org/10.1128/jcm.35.6.1295-1299.1997 Jami Al-Ahmadi G., Zahmatkesh Roodsari R. Fast and specific detection of Pseudomonas Aeruginosa from other pseudomonas species by PCR // Ann Burns Fire Disasters. – 2016;29(4):264-267. https://pubmed.ncbi.nlm.nih.gov/28289359 Jami Al-Ahmadi G., Zahmatkesh Roodsari R. Fast and specific detection of Pseudomonas Aeruginosa from other pseudomonas species by PCR // Ann Burns Fire Disasters. – 2016;29(4):264-267. https://pubmed.ncbi.nlm.nih.gov/28289359 Aghamollaei H., Moghaddam M.M., Kooshki H., Heiat M., Mirnejad R., Barzi N.S. Detection of Pseudomonas aeruginosa by a triplex polymerase chain reaction assay based on lasI/R and gyrB genes // J Infect Public Health. – 2015;8(4):314-322. htpps://doi.org/10.1016/j.jiph.2015.03.003 Aghamollaei H., Moghaddam M.M., Kooshki H., Heiat M., Mirnejad R., Barzi N.S. Detection of Pseudomonas aeruginosa by a triplex polymerase chain reaction assay based on lasI/R and gyrB genes // J Infect Public Health. – 2015;8(4):314-322. htpps://doi.org/10.1016/j.jiph.2015.03.003 Khuntayaporn P., Yamprayoonswat W., Yasawong M., Chomnawang M.T. Dissemination of carbapenem-resistance among multidrug resistant pseudomonas aeruginosa carrying metallo-beta-lactamase genes, including the novel blaimp-65 gene in Thailand // Infect Chemother. – 2019;51(2):107-118. htpps://doi.org/10.3947/ic.2019.51.2.107 Khuntayaporn P., Yamprayoonswat W., Yasawong M., Chomnawang M.T. Dissemination of carbapenem-resistance among multidrug resistant pseudomonas aeruginosa carrying metallo-beta-lactamase genes, including the novel blaimp-65 gene in Thailand // Infect Chemother. – 2019;51(2):107-118. htpps://doi.org/10.3947/ic.2019.51.2.107 Naas T., Aubert D., Lambert T., Nordmann P. Complex genetic structures with repeated elements, a sul-type class 1 integron, and the blaVEB extended-spectrum beta-lactamase gene // Antimicrob Agents Chemother. – 2006;50(5):1745-1752. htpps://doi.org/10.1128/AAC.50.5.1745-1752.2006 Naas T., Aubert D., Lambert T., Nordmann P. Complex genetic structures with repeated elements, a sul-type class 1 integron, and the blaVEB extended-spectrum beta-lactamase gene // Antimicrob Agents Chemother. – 2006;50(5):1745-1752. htpps://doi.org/10.1128/AAC.50.5.1745-1752.2006 Widmer F., Seidler R.J., Gillevet P.M., Watrud L.S., Di Giovanni G.D. A highly selective PCR protocol for detecting 16S rRNA genes of the genus Pseudomonas (sensu stricto) in environmental samples // Appl Environ Microbiol. – 1998;64(7):2545-2553. htpps://doi.org/10.1128/AEM.64.7.2545-2553.1998 Widmer F., Seidler R.J., Gillevet P.M., Watrud L.S., Di Giovanni G.D. A highly selective PCR protocol for detecting 16S rRNA genes of the genus Pseudomonas (sensu stricto) in environmental samples // Appl Environ Microbiol. – 1998;64(7):2545-2553. htpps://doi.org/10.1128/AEM.64.7.2545-2553.1998 Мавзютов А.Р., Мирсаяпова И.А., Хасанова Г.Ф., Баймиев А.Х. Сравнительная оценка информативности методов этиологической диагностики внебольничной пневмонии. Клиническая лабораторная диагностика. 2012;12:35-38. [A.R. Mavzjutov, I.A. Mirsajapova, G.F. Hasanova, A.H. Bajmiev. Comparative assessment of the information content of methods for the etiological diagnosis of community-acquired pneumonia. Clinical laboratory diagnostics. 2012;12:35-38. (In Russ.)]. https://www.elibrary.ru/item.asp?id=18762226 Mavzyutov A.R., Mirsayapova I.A., Hasanova G.F., Baymiev A.H. Sravnitel'naya ocenka informativnosti metodov etiologicheskoy diagnostiki vnebol'nichnoy pnevmonii. Klinicheskaya laboratornaya diagnostika. 2012;12:35-38. [A.R. Mavzjutov, I.A. Mirsajapova, G.F. Hasanova, A.H. Bajmiev. Comparative assessment of the information content of methods for the etiological diagnosis of community-acquired pneumonia. Clinical laboratory diagnostics. 2012;12:35-38. (In Russ.)]. https://www.elibrary.ru/item.asp?id=18762226 Huey B., Hall J. Hypervariable DNA fingerprinting in Escherichia coli: minisatellite probe from bacteriophage M13 // J Bacteriol. – 1989;171(5):2528-2532. htpps://doi.org/10.1128/jb.171.5.2528-2532.1989 Huey B., Hall J. Hypervariable DNA fingerprinting in Escherichia coli: minisatellite probe from bacteriophage M13 // J Bacteriol. – 1989;171(5):2528-2532. htpps://doi.org/10.1128/jb.171.5.2528-2532.1989 Кузнецова М.В., Максимова А.В., Карпунина Т.И. Опыт использования Rep- и RAPD-полимеразной цепной реакции для эпаидемиологической характеристики нозокоминальных изолятов Pseudomonas aeruginosa. Клиническая лабораторная диагностика. 2015;3:44-50. [M.V. Kuznecova, A.V. Maksimova, T.I. Karpunina. Experience of using Rep- and RAPD-polymerase chain reaction for epidemiological characterization of nosocomial isolates of Pseudomonas aeruginosa. Clinical laboratory diagnostics. 2015;3:44-50. (In Russ.)]. https://pubmed.ncbi.nlm.nih.gov/26031166 Kuznecova M.V., Maksimova A.V., Karpunina T.I. Opyt ispol'zovaniya Rep- i RAPD-polimeraznoy cepnoy reakcii dlya epaidemiologicheskoy harakteristiki nozokominal'nyh izolyatov Pseudomonas aeruginosa. Klinicheskaya laboratornaya diagnostika. 2015;3:44-50. [M.V. Kuznecova, A.V. Maksimova, T.I. Karpunina. Experience of using Rep- and RAPD-polymerase chain reaction for epidemiological characterization of nosocomial isolates of Pseudomonas aeruginosa. Clinical laboratory diagnostics. 2015;3:44-50. (In Russ.)]. https://pubmed.ncbi.nlm.nih.gov/26031166