Study on the Potential of Oxidative Stress on Certain Pathogenic Characteristics of Hospital-Acquired Klebsiella pneumoniae
Subject Areas : Biotechnological Journal of Environmental Microbiology
1 - Department of Microbiology, Faculty of Basic Sciences,Rasht Branch, Islamic Azad University
Keywords: Klebsiella pneumoniae, oxidative stress, virulence genes, biofilm, antimicrobial resistance, qRT-PCR,
Abstract :
Abstract
Klebsiella pneumoniae is a formidable nosocomial pathogen, with hypervirulent (hvKP) and multidrug-resistant (MDR) strains posing severe clinical threats. This study investigated the impact of oxidative stress on virulence gene expression and phenotypic adaptations in K. pneumoniae PTCC 1792, a hospital-acquired strain.
The strain was subjected to H2O2 treatments (0–9600 ppm) to assess oxidative stress tolerance. Biochemical profiling, biofilm assays, and antimicrobial susceptibility testing were performed. Virulence genes (rmpA, wcaG, ycf) were detected by PCR. Gene expression was quantified via qRT-PCR (2−ΔΔCt method), normalized to rpoB.
The strain exhibited exceptional H2O2 resistance (MIC = 2400 ppm) and increased catalase activity (4.8-fold). Biofilm formation was enhanced at 600 ppm (28%) but disrupted at 2400 ppm. rmpA and wcaG were significantly upregulated (4.2-fold and 3.8-fold, respectively) at sublethal stress, while ycf showed biphasic regulation (2.1-fold↑ at 600 ppm; 0.6-fold↓ at 2400 ppm). The strain harbored blaSHV-12 and blaCTX-M-15, confirming MDR phenotype.
Oxidative stress triggers virulence gene expression and biofilm modulation in K. pneumoniae PTCC 1792, highlighting its adaptive resilience. The unique ycf response suggests unexplored stress-response pathways. These findings underscore the need for novel strategies targeting oxidative defense mechanisms in hvKP infections.
Klebsiella pneumoniae, oxidative stress, virulence genes, biofilm, antimicrobial resistance, qRT-PCR
Abdel-Hady, H., Hawas, S., El-Daker, M., & El-Kady, R. (2008). Extended-spectrum beta-lactamase producing Klebsiella pneumoniae in neonatal intensive care unit. J Perinatology: Official J Calif Perinat Association, 28. https://doi.org/10.1038/jp.2008.73
Arcari, G., & Carattoli, A. (2023). Global spread and evolutionary convergence of multidrug-resistant and hypervirulent Klebsiella pneumoniae high-risk clones. Pathogens and Global Health, 117(4), 328-341.
Borghesi, A., Stronati, M., Castagnoli, R., Ioimo, I., Achille, C., Manzoni, P., & Tzialla, C. (2018). Novel approaches to the study of neonatal infections. Am J Perinatol, 35. https://doi.org/10.1055/s-0038-1639360
Chen, I.-R., Lin, S.-N., Wu, X.-N., Chou, S.-H., Wang, F.-D., & Lin, Y.-T. (2022). Clinical and microbiological characteristics of bacteremic pneumonia caused by Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology, 12, 903682.
De Celis, M., Belda, I., Marquina, D., & Santos, A. (2022). Phenotypic and transcriptional study of the antimicrobial activity of silver and zinc oxide nanoparticles on a wastewater biofilm-forming Pseudomonas aeruginosa strain. Science of the Total Environment, 826, 153915.
Fu, P., Xu, H., Jing, C., Deng, J., Wang, H., Hua, C., Chen, Y., Chen, X., Zhang, T., & Zhang, H. (2021). Bacterial epidemiology and Antimicrobial Resistance profiles in Children reported by the ISPED Program in China, 2016 to 2020. Microbiol Spectr, 9. https://doi.org/10.1128/Spectrum.00283-21
Hu, Y., Yang, Y., Feng, Y., Fang, Q., Wang, C., Zhao, F., McNally, A., & Zong, Z. (2023). Prevalence and clonal diversity of carbapenem-resistant Klebsiella pneumoniae causing neonatal infections: a systematic review of 128 articles across 30 countries. PLoS Med, 20. https://doi.org/10.1371/journal.pmed.1004233
Jiang, N., Wang, Y., Wang, Q., Li, H., Mai, J., & Lin, Z. (2014). [Clinical analysis of nosocomial infection and risk factors of extremely premature infants]. Zhonghua Er Ke Za Zhi = Chin J Pediatr, 52.
Jiang, Z., & Ye, G. Y. (2013). 1:4 matched case-control study on influential factor of early onset neonatal sepsis. Eur Rev Med Pharmacol Sci, 17.
Johnson, A. G., Wein, T., Mayer, M. L., Duncan-Lowey, B., Yirmiya, E., Oppenheimer-Shaanan, Y., Amitai, G., Sorek, R., & Kranzusch, P. J. (2022). Bacterial gasdermins reveal an ancient mechanism of cell death. Science, 375(6577), 221-225.
Kelly, M. S., Benjamin, D. K., & Smith, P. B. (2015). The epidemiology and diagnosis of invasive candidiasis among premature infants. Clin Perinatol, 42. https://doi.org/10.1016/j.clp.2014.10.008
Levy, O. (2007). Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol, 7. https://doi.org/10.1038/nri2075
Lin, T.-L., Hsieh, P.-F., Huang, Y.-T., Lee, W.-C., Tsai, Y.-T., Su, P.-A., Pan, Y.-J., Hsu, C.-R., Wu, M.-C., & Wang, J.-T. (2014). Isolation of a bacteriophage and its depolymerase specific for K1 capsule of Klebsiella pneumoniae: implication in typing and treatment. The Journal of infectious diseases, 210(11), 1734-1744.
Liu, L., Oza, S., Hogan, D., Perin, J., Rudan, I., Lawn, J. E., Cousens, S., Mathers, C., & Black, R. E. (2015). Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet (London England), 385. https://doi.org/10.1016/S0140-6736(14)61698-6
Macharashvili, N., Kourbatova, E., Butsashvili, M., Tsertsvadze, T., McNutt, L. A., & Leonard, M. K. (2009). Etiology of neonatal blood stream infections in Tbilisi, Republic of Georgia. Int J Infect Diseases: IJID : Official Publication Int Soc Infect Dis, 13.
Mashau, R. C., Meiring, S. T., Dramowski, A., Magobo, R. E., Quan, V. C., Perovic, O., Gottberg, A., Cohen, C., Velaphi, S., & Schalkwyk, E. (2022). Culture-confirmed neonatal bloodstream infections and meningitis in South Africa, 2014-19: a cross-sectional study. Lancet Global Health, 10. https://doi.org/10.1016/S2214-109X(22)00246-7
Nour, I., Eldegla, H. E., Nasef, N., Shouman, B., Abdel-Hady, H., & Shabaan, A. E. (2017). Risk factors and clinical outcomes for carbapenem-resistant gram-negative late-onset sepsis in a neonatal intensive care unit. J Hosp Infect, 97. https://doi.org/10.1016/j.jhin.2017.05.025
Osei Sekyere, J., Reta, M. A., & Bernard Fourie, P. (2021). Risk factors for, and molecular epidemiology and clinical outcomes of, carbapenem- and polymyxin-resistant Gram-negative bacterial infections in pregnant women, infants, and toddlers: a systematic review and meta-analyses. Ann N Y Acad Sci, 1502. https://doi.org/10.1111/nyas.14650
Pessoa-Silva, C. L., Meurer Moreira, B., Câmara Almeida, V., Flannery, B., Almeida Lins, M. C., Mello Sampaio, J. L., Martins Teixeira, L., Vaz Miranda, L. E., Riley, L. W., & Gerberding, J. L. (2003). Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit: risk factors for infection and colonization. J Hosp Infect, 53. https://doi.org/10.1053/jhin.2002.1373
Pinelli, F., Perale, G., & Rossi, F. (2020). Coating and functionalization strategies for nanogels and nanoparticles for selective drug delivery. Gels, 6. https://doi.org/10.3390/gels6010006
Russo, T. A., & Marr, C. M. (2019). Hypervirulent klebsiella pneumoniae. Clinical Microbiology Reviews, 32(3), 10.1128/cmr. 00001-00019.
Shane, A. L., Sánchez, P. J., & Stoll, B. J. (2017). Neonatal sepsis. Lancet (London England), 390. https://doi.org/10.1016/S0140-6736(17)31002-4
Siopi, M., Skliros, D., Paranos, P., Koumasi, N., Flemetakis, E., Pournaras, S., & Meletiadis, J. (2024). Pharmacokinetics and pharmacodynamics of bacteriophage therapy: a review with a focus on multidrug-resistant Gram-negative bacterial infections. Clinical Microbiology Reviews, 37(3), e00044-00024.
Stapleton, P. J., Murphy, M., McCallion, N., Brennan, M., Cunney, R., & Drew, R. J. (2016). Outbreaks of extended spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review. Archives Disease Child Fetal Neonatal Ed, 101. https://doi.org/10.1136/archdischild-2015-308707
Taddese, A. A., Gashaye, K. T., Dagne, H., & Andualem, Z. (2020). Maternal and partner’s level of satisfaction on the delivery room service in University of Gondar Referral Hospital, northwest, Ethiopia: a comparative cross-sectional study. BMC health services research, 20, 1-8.
Xiao, S., Zhou, S., Cao, H., Han, L., Zhao, S., & Wang, X. (2024). Incidence, antimicrobial resistance and mortality of Klebsiella pneumoniae bacteraemia in Shanghai, China, 2018–2022. Infectious Diseases, 56(12), 1021-1030.
Zar, H. J., MacGinty, R., Workman, L., Burd, T., Smith, G., Myer, L., Häggström, J., & Nicol, M. P. (2022). Klebsiella pneumoniae lower respiratory tract infection in a South African birth cohort: a longitudinal study. Int J Infect Diseases: IJID : Official Publication Int Soc Infect Dis, 121.
Zhang, J., Xu, L., Zhang, K., Yue, J., Dong, K., Luo, Q., Yu, W., & Huang, Y. (2024). Synergistic effect of fosfomycin and colistin against KPC-producing Klebsiella pneumonia e: pharmacokinetics-pharmacodynamics combined with transcriptomic approach. BMC microbiology, 24(1), 430.
Zong, Z., Wu, A., & Hu, B. (2020). Infection control in the era of Antimicrobial Resistance in China: Progress, challenges, and opportunities. Clin Infect Diseases: Official Publication Infect Dis Soc Am, 71. https://doi.org/10.1093/cid/ciaa1514