KLEBSIELLA PNEUMONIAE AS AN ETIOLOGICAL FACTOR IN INFECTIOUS PROCESSES IN CHILDREN
Abstract
The purpose of the review is to establish how violations of the interaction between the opportunistic bacteria Klebsiella pneumoniae, the intestinal microbiome and the innate immune system lead to the development of infectious processes. K. pneumoniae, being a representative of the microbiome of a healthy person, can serve as a source of opportunistic infection. Colonization of the intestine by Klebsiella spp. should be considered as a necessary condition for the development of infectious processes. At the same time, K. pneumoniae can be given to subjects with weakened immunity from practically healthy individuals. The outcome of colonization of the intestinal mucosa of children with Klebsiella spp. depends on the factors of virulence, resistance of the mucous membrane to colonization and immunity. In recent years, experimental models have proved that K. pneumoniae is able to colonize the intestine even without pretreatment with antibiotics, which is accompanied by inflammatory changes in the mucous membrane. These observations suggest that K. pneumoniae can be considered as a potential etiological agent not only in generalized forms of infection in newborns, but also in intestinal infections in young children with unformed intestinal microbiota and immune system. Klebsiella spp. strains with genes that increase colonization density in the intestine, together with virulence genes, pose the greatest risk of infection in colonized patients. The risk of infection with bacteria Klebsiella spp. is also influenced by the patient’s health variables. Colonization of the intestines of K. pneumoniae should be considered as an example of pathogen evasion from host immunity reactions, and K. pneumoniae immune strategies as a means of overcoming the protective reactions of the host organism and the subsequent development of the infectious process.
References
Белозеров Е.С., Буланьков Ю.И., Васильев В.В. и др. Руководство по инфекционным болезням. СПб.: Фолиант; 2011.
Агеевец В.А., Агеевец И.В., Сидоренко С.В. Конвергенция множественной резистентности и гипервирулентности у Klebsiella pneumoniae. Инфекция и иммунитет. 2022;12(3):450–460. DOI: 10.15789/2220-7619-COM-1825.
Гончар Н.В., Скрипченко Н.В. Перспективные направления научных исследований по проблемам кишечных инфекций. Детская медицина Северо-Запада. 2023;11(2):50–61. DOI: 10.56871/CmN-W.2023.46.73.004.
Darboe S., Carvaheiro C.G., Kobeissi E. et al. Articles Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis Antimicrobial Resistance Collaborators. Lancet. 2022;399:629–655. DOI: 10.1016/S0140-6736(21)02724-0.
Lam M.M.C., Wyres K.L., Wick R.R. et al. Convergence of virulence and MDR in a single plasmid vector in MDR Klebsiella pneumoniae ST15. Antimicrob Chemother. 2019;74:1218–1222. DOI: 10.1093/jac/dkz028.
Gorrie C.L., Mirceta M., Wick R.R. et al. Gastrointestinal carriage is a major reservoir of Klebsiella pneumoniae infection in intensive care patients. Clin Infect Dis. 2017;65:208–215. DOI: 10.1093/cid/cix270.
Joseph L., Merciecca T., Forestier C. et al. From Klebsiella pneumoniae colonization to dissemination: an overview of studies implementing murine models. Microorganisms. 2021;9:1282. DOI: 10.3390/microorganisms9061282.
Raffelsberger N., Hetland M.A.K., Svendsen K. et al. Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population: a cross-sectional study of risk factors and bacterial genomic diversity. Gut Microbes. 2021;13:1939599. DOI: 10.1080/19490976.2021.1939599.
Calderon-Gonzalez R., Lopez-Campos G., Hancock S.J. et al. Modelling the Gastrointestinal Carriage of Klebsiella pneumoniae Infections. mBio. 2023;14(1):e0312122. DOI: 10.1128/mbio.03121-22.
Мазанкова Л.Н., Рыбальченко О.В., Николаева И.В. Микродисбиоз и эндогенные инфекции. М.: ГЭОТАР-Медиа; 2018.
Харченко Г.А., Кимирилова О.Г. Клинико-эпидемиологические особенности острых кишечных инфекций, вызванных условно-патогенными энтеробактериями у детей раннего возраста. Лечащий Врач. 2021;4(24):37–41.
Гончар Н.В., Коперсак А.К., Раздьяконова И.В. и др. Клинико-лабораторные особенности острых кишечных инфекций, вызванных Klebsiella pneumoniae, у детей. Children’s Medicine of the North-West. 2023;11(3):110–119. DOI: 10.56871/CmN-W.2023.90.13.008.
Гончар Н.В., Коперсак А.К., Скрипченко Н.В. и др. Клинические особенности затяжного течения кишечной инфекции, ассоциированной с Klebsiella pneumonia, у ребенка грудного возраста. Медицина экстремальных ситуаций. 2024;1(26):112–118. DOI: 10.47183/mes.2024.006.
Курышева О.А., Налетов А.В., Масюта Д.И. Синдром Вискотта-Олдрича (случай из практики): аллогенная трансплантация костного мозга. Children’s Medicine of the North-West. 2024;12(4):224–231. DOI: 10.56871/CmN-W.2024.26.82.019.
Семенова Д.Р., Николаева И.В., Фиалкина С.В. и др. Частота колонизации «гипервирулентными» штаммами Klebsiella pneumoniae новорожденных и грудных детей с внебольничной и нозокомиальной клебсиеллезной инфекцией. Российский вестник перинатологии и педиатрии. 2020;65(5):158–163. DOI: 10.21508/1027-4065-2020-65-5-158-163.
Рыбальченко О.В., Бондаренко В.М., Добрица В.П. Атлас ультраструктуры микробиоты кишечника человека. СПб.: ИИЦ ВМА; 2008.
Martin R.M., Bachman M.A. Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front Cell Infect Microbiol. 2018;8:4. DOI: 10.3389/fcimb.2018.00004.
Russo T.A., Marr C.M. Hypervirulent Klebsiella pneumoniae. Clin Microbiol Rev. 2019;32(3):e00001-19. DOI: 10.1128/CMR.00001-19.
Catalán-Nájera J.C., Garza-Ramos U., Barrios-Camacho H. Hypervirulence and hypermucoviscosity: Two different but complementary Klebsiella spp. phenotypes? Virulence. 2017;8:1111–1123.
Кузнецова М.В., Сергевнин В.И., Михайловская В.С. и др. Микробиологическая и молекулярно-генетическая характеристика изолятов Klebsiella pneumoniae, выделенных в условиях кардиохирургического стационара. Инфекция и иммунитет. 2024;14(1):103–114. doi: 10.15789/2220-7619-MAM-15631.
Navon-Venezia S., Kondratyeva K., Carattoli A. Klebsiella pneumoniae: A major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev. 2017;41:252–275.
Russo T.A., Olson R., Fang C.T. et al. Identification of Biomarkers for Differentiation of Hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae. J Clin Microbiol. 2018;56(9):e00776-18. doi: 10.1128/JCM.00776-18.
Wang G., Zhao G., Chao X. et al. The Characteristic of Virulence, Biofilm and Antibiotic Resistance of Klebsiella pneumoniae. Int J Environ Res Public Health. 2020;17:6278. doi: 10.3390/ijerph17176278.
Kocsis B. Hypervirulent Klebsiella pneumoniae: An update on epidemiology, detection and antibiotic resistance. Acta Microbiologica et Immunologica Hungarica. 2023;70(4):278–287. doi: 10.1556/030.2023.02186.
Li G., Sun S., Zhao Z.Y., Sun Y. The pathogenicity of rmpA or aerobactin-positive Klebsiella pneumoniae in infected mice. J Int Med Res. 2019;47:4344–4352.
Lepuschitz S., Schill S., Stoeger A. et al. Whole genome sequencing reveals resemblance between ESBL-producing and carbapenem resistant Klebsiella pneumoniae isolates from Austrian rivers and clinical isolates from hospitals. Sci Total Environ. 2019;662:227–235.
Stojowska-Sw˛edrzy´nska K., Łupkowska A., Kuczy´nska-Wi´snik D., Laskowska E. Antibiotic Heteroresistance in Klebsiella pneumoniae. Int J Mol Sci. 2022;23:449. doi: 10.3390/ijms23010449.
Sharma D., Garg A., Kumar M., Khan A.U. Proteome profiling of carbapenem-resistant K. pneumoniae clinical isolate (NDM-4): Exploring the mechanism of resistance and potential drug targets. J Proteom. 2019;200:102–110.
Ballen V., Gabasa Y., Ratia C. et al. Antibiotic Resistance and Virulence Profiles of Klebsiella pneumoniae Strains Isolated From Different Clinical Sources. Front Cell Infect Microbiol. 2021;11:738223. doi: 10.3389/fcimb.2021.738223.
Vornhagen J., Rao K., Bachman M. Gut community structure as a risk factor for infection in Klebsiella-colonized patients. mSystems. 2024;9(8):e0078624. DOI: 10.1128/msystems.00786-24.
Wyres K.L., Lam M.M.C., Holt K.E. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol. 2020;18:344–359. DOI: 10.1038/s41579-019-0315-1.
Perez-Nadales E., Natera A.M., Recio-Rufian M. et al. Prognostic Significance of the Relative Load of KPC-Producing Klebsiella pneumoniae within the Intestinal Microbiota in a Prospective Cohort of Colonized Patients. Microbiol Spectr. 2022;10(4):e0272821. DOI: 10.1128/spectrum.02728-21.
Kang J.T., Teo J.Y., Bertrand D. et al. Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects. Nat Microbio. 2022;7(10):1516–1524. DOI: 10.1038/s41564-022-01221-w.
Sun Y., Patel A., SantaLucia J. et al. Measurement of Klebsiella intestinal colonization density to assess infection risk. mSphere. 2021;6:e00500-21. DOI: 10.1128/mSphere.00500-21.
Гончар Н.В., Скрипченко Н.В., Коперсак А.К. Колонизационная резистентность и микробиота кишечника как факторы противодействия развитию кишечных инфекций (обзор). Детская медицина Северо-Запада. 2023;11(4):25–38. DOI: 10.56871/CmN-W.2023.43.34.003.
Rao K., Seekatz A., Bassis C. et al. Enterobacterales infection after intestinal dominance in hospitalized patients. mSphere. 2020;5:e00450–20. DOI: 10.1128/mSphere.00450-20.
Shimasaki T., Seekatz A., Bassis C. et al. Increased relative abundance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae within the gut microbiota is associated with risk of bloodstream infection in long-term acute care hospital patients. Clin Infect Dis. 2019;68(12):2053–2059. DOI: 10.1093/cid/ciy796.
Magruder M., Sholi A.N., Gong C. et al. Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection. Nat Commun. 2019;10:5521. DOI: 10.1038/s41467-019-13467-w.
Long S.W., Linson S.E., Ojeda Saavedra M. et al. Whole-
genome sequencing of human clinical Klebsiella pneumoniae isolates reveals misidentification and misunderstandings of Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae. mSphere. 2017;2:e00290–17. DOI: 10.1128/mSphereDirect.00290-17.
Martin R.M., Cao J., Wu W. et al. Identification of pathogenicity-associated loci in Klebsiella pneumoniae from hospitalized patients. mSystems. 2018;3:e00015–18. DOI: 10.1128/mSystems.00015-18.
Rao K., Patel A., Sun Y. et al. Risk Factors for Klebsiella Infections among Hospitalized Patients with Preexisting Colonization. mSphere. 2021;6(3):e0013221. DOI: 10.1128/mSphere.00132-21.
Гончар Н.В., Коперсак А.К., Скрипченко Н.В. и др. Резистентность к антибактериальным препаратам и бактериофагам изолятов Klebsiella pneumoniae, выделенных от детей разного возраста с кишечными инфекциями. Детские инфекции. 2023;22(1):27–31. DOI: 10.22627/2072-8107-2023-22-1-27-31.
Rogers M.A., Greene M.T., Young V.B. et al. Depression, antidepressant medications, and risk of Clostridium difficile infection. BMCMed. 2013;11:121. DOI: 10.1186/1741-7015-11-121.
Choby J.E., Howard-Anderson J., Weiss D.S. Hypervirulent Klebsiella pneumoniae — clinical and molecular perspectives. Intern Med. 2020;287(3):283–300. doi: 10.1111/joim.13007.
Sands B.E. Biomarkers of inflammation in inflammatory bowel disease. Gastroenterology. 2015;149:1275–1285. DOI: 10.1053/j.gastro.2015.07.003.
AL-Salihi S.S., Al-Jubouri A.S., Albayati A.F., Mahmood Y.A.R. Enterotoxin Detection by PCR in Klebsiella pneumoniae Isolated from Diarrheal Cases among Children in Kirkuk City — Iraq. American Journal of Medical Sciences and Medicine. 2016;4(5):92–96. DOI:10.12691/ajmsm-4-5-1.
Janczura A., Smutnicka D., Junka A., Gościniak G. The detection and expression of enterotoxin encoding lth gene among Klebsiella spp. isolated from diarrhoea. Cent Eur J Biol. 2013;8(2):121–129. DOI: 10.2478/s11535-013-0115-y.
Ernst C.M., Braxton J.R., Rodriguez-Osorio C.A. et al. Adaptive evolution of virulence and persistence in carbapenem-resistant Klebsiella pneumoniae. Nat Med. 2020;26:705–711. DOI: 10.1038/s41591-020-0825-4.
Bengoechea J.A., Sa Pessoa J. Klebsiella pneumoniae infection biology: living to counteract host defences. FEMS Microbiol Rev. 2019;43:123–144. DOI: 10.1093/femsre/fuy043.
Марковская И.Н., Лисица И.А., Кузнецова Ю.В. и др. Динамика развития микробиома ребенка, длительно госпитализированного в отделении интенсивной терапии. Клинический случай. Children’s Medicine of the North-West. 2024;12(1):123–135. DOI: 10.56871/
CmN-W.2024.50.20.013.
Гончар Н.В., Бабаченко И.В., Гостев В.В., Ибрагимова О.М. Характеристика микробиоты кишечника детей первого года жизни по данным секвенирования гена 16S рРНК. Журнал инфектологии. 2017;9(2):23–28. DOI: 10.22625/2072-6732-2017-9-2-23-28.
Ермоленко К.Д., Гончар Н.В., Кириленко Л.А. Скрипченко Н.В. Оценка эффективности применения бактериофагов при лечении острых кишечных инфекций, вызванных условно-патогенными микроорганизмами, у детей первого года жизни. Педиатрия им. Г.Н. Сперанского. 2024;103(1):114–123. DOI: 10.24110/0031-403X-2024-103-1-114-123.
Суворов А.Н. Микробиота как ключ к стратегии выживания человека. Жебраковские чтения. Сборник тезисов конференции. Минск. 2021:44–67.
Feriotti C., Sa-Pessoa J., Calderon-Gonzalez R. et al. Klebsiella pneumonia hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity. Cell Reports. 2022;40(6):111167. DOI: 10.1016/j.celrep.2022.111167.
