The Importance of Klebsiella pneumoniae as a Pathogen and the Increasing Prevalence of Antibiotic-Resistant Strains and Molecular Characteristics
DOI:
https://doi.org/10.47419/bjbabs.v4i04.211Keywords:
mechanisms of antibiotic resistance, Antibiotic-Resistant Strains, k.pneumoniae, Molecular characteristics, Genetics, Gene transfer mechanismsAbstract
Klebsiella pneumoniae is a significant pathogen causing various infections, and antibiotic-resistant strains of K.pneumoniae are becoming more prevalent. Molecular studies reveal the genetic mechanisms underlying antibiotic resistance, such as resistance genes on plasmids that can easily spread between bacteria. Knowledge of the molecular characteristics of antibiotic-resistant strains is crucial to develop effective strategies against their spread. The bacteria can easy colonizes the human gut and can also cause a range of infections, including pneumonia, urinary tract infections, and bloodstream infections.
The emergence of antibiotic-resistant strains of K.pneumoniae has become a major public health concern, as these strains are associated with increased morbidity and mortality rates, longer hospital stays, and higher healthcare costs. Antibiotic resistance in K.pneumoniae involves several mechanisms, including beta-lactamase production, changes in outer membrane porins, and the uptake of resistance genes via horizontal gene transfer.
The genetics and genomics of K.pneumoniae are also of significant interest, as they provide insights into the diversity of strains and their pathogenic potential. Genome sequencing has revealed the existence of distinct lineages of K. pneumoniae, each with unique virulence factors and antimicrobial resistance profiles.
To summarize, K.pneumoniae is a critical pathogen that poses a substantial global public health threat. The rising prevalence of antibiotic-resistant strains underscores the pressing need for innovative approaches to prevent and treat K.pneumoniae infections. Comprehensive knowledge of the molecular mechanisms of virulence, pathogenicity, and antibiotic resistance, as well as the genetic diversity of K. pneumoniae, will be essential in developing effective strategies to combat this pathogen.
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Årdal, C., Balasegaram, M., Laxminarayan, R., McAdams, D., Outterson, K., Rex, J. H., & Sumpradit, N. (2020). Antibiotic development—economic, regulatory and societal challenges. Nature Reviews Microbiology, 18(5), 267-274.
Baker, S., Thomson, N., Weill, F.-X., & Holt, K. E. (2018). Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens. Science, 360(6390), 733-738.
Baraldi, E., & Wagrell, S. (2022). Applying the resource interaction approach to policy analysis–Insights from the antibiotic resistance challenge. Industrial Marketing Management, 106, 376-391.
Bengoechea, J. A., & Sa Pessoa, J. (2019). Klebsiella pneumoniae infection biology: living to counteract host defences. FEMS microbiology reviews, 43(2), 123-144.
Bhan, U., Ballinger, M. N., Zeng, X., Newstead, M. J., Cornicelli, M. D., & Standiford, T. J. (2010). Cooperative interactions between TLR4 and TLR9 regulate interleukin 23 and 17 production in a murine model of gram negative bacterial pneumonia. PLoS One, 5(3), e9896.
Boszczowski, I., Salomão, M. C., Moura, M. L., Freire, M. P., Guimarães, T., Cury, A. P., Rossi, F., Rizek, C. F., Martins, R. C. R., & Costa, S. F. (2019). Multidrug-resistant Klebsiella pneumoniae: genetic diversity, mechanisms of resistance to polymyxins and clinical outcomes in a tertiary teaching hospital in Brazil. Revista do Instituto de Medicina Tropical de São Paulo, 61.
Cai, W., Cai, L., Zhao, J., & Yao, H. (2023). Prokaryotic community interchange between distinct microhabitats causes community pressure on anammox biofilm development. Water Research, 233, 119726.
Campos-Madueno, E. I., Moradi, M., Eddoubaji, Y., Shahi, F., Moradi, S., Bernasconi, O. J., Moser, A. I., & Endimiani, A. (2023). Intestinal colonization with multidrug-resistant Enterobacterales: screening, epidemiology, clinical impact, and strategies to decolonize carriers. European Journal of Clinical Microbiology & Infectious Diseases, 1-26.
Chen, Y., Chen, Y., Liu, P., Guo, P., Wu, Z., Peng, Y., Deng, J., Kong, Y., Cui, Y., & Liao, K. (2022). Risk factors and mortality for elderly patients with bloodstream infection of carbapenem resistance Klebsiella pneumoniae: a 10-year longitudinal study. BMC geriatrics, 22(1), 1-8.
Cillóniz, C., Dominedò, C., & Torres, A. (2019). Multidrug resistant gram-negative bacteria in community-acquired pneumonia. Annual Update in Intensive Care and Emergency Medicine 2019, 459-475.
Clegg, S., & Murphy, C. N. (2017). Epidemiology and virulence of Klebsiella pneumoniae. Urinary Tract Infections: Molecular Pathogenesis and Clinical Management, 435-457.
Cook, M. A., & Wright, G. D. (2022). The past, present, and future of antibiotics. Science Translational Medicine, 14(657), eabo7793.
Dell’Annunziata, F., Dell’Aversana, C., Doti, N., Donadio, G., Dal Piaz, F., Izzo, V., De Filippis, A., Galdiero, M., Altucci, L., & Boccia, G. (2021). Outer membrane vesicles derived from Klebsiella pneumoniae are a driving force for horizontal gene transfer. International Journal of Molecular Sciences, 22(16), 8732.
Doorduijn, D. J., Rooijakkers, S. H., van Schaik, W., & Bardoel, B. W. (2016). Complement resistance mechanisms of Klebsiella pneumoniae. Immunobiology, 221(10), 1102-1109.
Galani, I., Karaiskos, I., & Giamarellou, H. (2021). Multidrug-resistant Klebsiella pneumoniae: mechanisms of resistance including updated data for novel β-lactam-β-lactamase inhibitor combinations. Expert Review of Anti-infective Therapy, 19(11), 1457-1468.
Galbadage, T., Liu, D., Alemany, L. B., Pal, R., Tour, J. M., Gunasekera, R. S., & Cirillo, J. D. (2019). Molecular nanomachines disrupt bacterial cell wall, increasing sensitivity of extensively drug-resistant Klebsiella pneumoniae to meropenem. ACS nano, 13(12), 14377-14387.
Gan, L., Yan, C., Cui, J., Xue, G., Fu, H., Du, B., Zhao, H., Feng, J., Feng, Y., & Fan, Z. (2022). Genetic diversity and pathogenic features in Klebsiella pneumoniae isolates from patients with pyogenic liver abscess and pneumonia. Microbiology Spectrum, 10(2), e02646-02621.
Gupta, P., Sarkar, S., Das, B., Bhattacharjee, S., & Tribedi, P. (2016). Biofilm, pathogenesis and prevention—a journey to break the wall: a review. Archives of Microbiology, 198, 1-15.
Hachani, A., Wood, T. E., & Filloux, A. (2016). Type VI secretion and anti-host effectors. Current opinion in microbiology, 29, 81-93.
Haudiquet, M., Buffet, A., Rendueles, O., & Rocha, E. P. (2021). Interplay between the cell envelope and mobile genetic elements shapes gene flow in populations of the nosocomial pathogen Klebsiella pneumoniae. PLoS Biology, 19(7), e3001276.
Holt, K. E., Wertheim, H., Zadoks, R. N., Baker, S., Whitehouse, C. A., Dance, D., Jenney, A., Connor, T. R., Hsu, L. Y., & Severin, J. (2015). Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proceedings of the National Academy of Sciences, 112(27), E3574-E3581.
Hsieh, P.-F., Lin, T.-L., Yang, F.-L., Wu, M.-C., Pan, Y.-J., Wu, S.-H., & Wang, J.-T. (2012). Lipopolysaccharide O1 antigen contributes to the virulence in Klebsiella pneumoniae causing pyogenic liver abscess. PLoS One, 7(3), e33155.
Hsu, C.-R., Lin, T.-L., Pan, Y.-J., Hsieh, P.-F., & Wang, J.-T. (2013). Isolation of a bacteriophage specific for a new capsular type of Klebsiella pneumoniae and characterization of its polysaccharide depolymerase. PLoS One, 8(8), e70092.
Kakoullis, L., Papachristodoulou, E., Chra, P., & Panos, G. (2021). Mechanisms of antibiotic resistance in important gram-positive and gram-negative pathogens and novel antibiotic solutions. Antibiotics, 10(4), 415.
Kaye, K. S., & Pogue, J. M. (2015). Infections caused by resistant gram‐negative bacteria: epidemiology and management. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 35(10), 949-962.
Khan, S., Khan, S. N., Akhtar, F., Misba, L., Meena, R., & Khan, A. U. (2020). Inhibition of multi-drug resistant Klebsiella pneumoniae: Nanoparticles induced photoinactivation in presence of efflux pump inhibitor. European Journal of Pharmaceutics and Biopharmaceutics, 157, 165-174.
Kim, J. I., Maguire, F., Tsang, K. K., Gouliouris, T., Peacock, S. J., McAllister, T. A., McArthur, A. G., & Beiko, R. G. (2022). Machine learning for antimicrobial resistance prediction: current practice, limitations, and clinical perspective. Clinical microbiology reviews, 35(3), e00179-00121.
Kobylka, J., Kuth, M. S., Müller, R. T., Geertsma, E. R., & Pos, K. M. (2020). AcrB: a mean, keen, drug efflux machine. Annals of the New York Academy of Sciences, 1459(1), 38-68.
Lai, C. K., Ng, R. W., Leung, S. S., Hui, M., & Ip, M. (2022). Overcoming the rising incidence and evolving mechanisms of antibiotic resistance by novel drug delivery approaches–an overview. Advanced Drug Delivery Reviews, 181, 114078.
Letourneau, A. R., & Calderwood, S. (2019). Beta-lactam antibiotics: mechanisms of action and resistance and adverse effects. UptoDate. Waltham (MA): UptoDate.
Li, B., & Webster, T. J. (2018). Bacteria antibiotic resistance: New challenges and opportunities for implant‐associated orthopedic infections. Journal of Orthopaedic Research®, 36(1), 22-32.
Li, Z., Liu, X., Lei, Z., Li, C., Zhang, F., Wu, Y., Yang, X., Zhao, J., Zhang, Y., & Hu, Y. (2023). Genetic Diversity of Polymyxin-Resistance Mechanisms in Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae: a Multicenter Study in China. Microbiology Spectrum, e05231-05222.
Lima, L. M., da Silva, B. N. M., Barbosa, G., & Barreiro, E. J. (2020). β-lactam antibiotics: An overview from a medicinal chemistry perspective. European journal of medicinal chemistry, 208, 112829.
McInnes, R. S., McCallum, G. E., Lamberte, L. E., & van Schaik, W. (2020). Horizontal transfer of antibiotic resistance genes in the human gut microbiome. Current opinion in microbiology, 53, 35-43.
Nepal, R., Houtak, G., Karki, S., Dhungana, G., Vreugde, S., & Malla, R. (2022). Genomic characterization of three bacteriophages targeting multidrug resistant clinical isolates of Escherichia, Klebsiella and Salmonella. Archives of Microbiology, 204(6), 334.
Nimer, N. A. (2022). Nosocomial infection and antibiotic-resistant threat in the middle east. Infection and drug resistance, 631-639.
Opoku-Temeng, C., Kobayashi, S. D., & DeLeo, F. R. (2019). Klebsiella pneumoniae capsule polysaccharide as a target for therapeutics and vaccines. Computational and structural biotechnology journal, 17, 1360-1366.
Pacios, O., Fernández-García, L., Bleriot, I., Blasco, L., Ambroa, A., López, M., Ortiz-Cartagena, C., González de Aledo, M., Fernández-Cuenca, F., & Oteo-Iglesias, J. (2022). Adaptation of clinical isolates of Klebsiella pneumoniae to the combination of niclosamide with the efflux pump inhibitor phenyl-arginine-β-naphthylamide (PaβN): co-resistance to antimicrobials. Journal of Antimicrobial Chemotherapy, 77(5), 1272-1281.
Partridge, S. R., Kwong, S. M., Firth, N., & Jensen, S. O. (2018). Mobile genetic elements associated with antimicrobial resistance. Clinical microbiology reviews, 31(4), e00088-00017.
Paulin-Curlee, G., Singer, R., Sreevatsan, S., Isaacson, R., Reneau, J., Foster, D., & Bey, R. (2007). Genetic diversity of mastitis-associated Klebsiella pneumoniae in dairy cows. Journal of dairy science, 90(8), 3681-3689.
Puvača, N., Tankosić, J. V., Ignjatijević, S., Carić, M., & Prodanović, R. (2022). Antimicrobial Resistance in the Environment: Review of the Selected Resistance Drivers and Public Health Concerns. J. Agron. Technol. Eng. Manag., 5, 793-802.
Regueiro, V., Campos, M. A., Pons, J., Albertí, S., & Bengoechea, J. A. (2006). The uptake of a Klebsiella pneumoniae capsule polysaccharide mutant triggers an inflammatory response by human airway epithelial cells. Microbiology, 152(2), 555-566.
Regueiro, V., Moranta, D., Frank, C. G., Larrarte, E., Margareto, J., March, C., Garmendia, J., & Bengoechea, J. A. (2011). Klebsiella pneumoniae subverts the activation of inflammatory responses in a NOD1‐dependent manner. Cellular microbiology, 13(1), 135-153.
Riaz, N., Imran, R., Mukhtar, H., & Gohar, U. F. (2021). Contribution of klebseilla pneumonia to antibiotic resistance of human infection: A review. Pakistan J. Med. Heal. Sci, 15(1), 6-11.
Riquelme, S. A., Ahn, D., & Prince, A. (2018). Pseudomonas aeruginosa and Klebsiella pneumoniae adaptation to innate immune clearance mechanisms in the lung. Journal of innate immunity, 10(5-6), 442-454.
Roca, I., Akova, M., Baquero, F., Carlet, J., Cavaleri, M., Coenen, S., Cohen, J., Findlay, D., Gyssens, I., & Heure, O. (2015). The global threat of antimicrobial resistance: science for intervention. New microbes and new infections, 6, 22-29.
Russo, T. A., Shon, A. S., Beanan, J. M., Olson, R., MacDonald, U., Pomakov, A. O., & Visitacion, M. P. (2011). Hypervirulent K.pneumoniae secretes more and more active iron-acquisition molecules than “classical” K.pneumoniae thereby enhancing its virulence. PLoS One, 6(10), e26734.
Salmanov, A., Vozianov, S., Kryzhevsky, V., Litus, O., Drozdova, A., & Vlasenko, I. (2019). Prevalence of healthcare-associated infections and antimicrobial resistance in acute care hospitals in Kyiv, Ukraine. Journal of Hospital Infection, 102(4), 431-437.
Schneider, C. L. (2021). Bacteriophage-mediated horizontal gene transfer: transduction. Bacteriophages: biology, technology, therapy, 151-192.
Sharma, A., Singh, A., Dar, M. A., Kaur, R. J., Charan, J., Iskandar, K., Haque, M., Murti, K., Ravichandiran, V., & Dhingra, S. (2022). Menace of antimicrobial resistance in LMICs: Current surveillance practices and control measures to tackle hostility. Journal of Infection and Public Health, 15(2), 172-181.
Shelenkov, A., Mikhaylova, Y., Yanushevich, Y., Samoilov, A., Petrova, L., Fomina, V., Gusarov, V., Zamyatin, M., Shagin, D., & Akimkin, V. (2020). Molecular typing, characterization of antimicrobial resistance, virulence profiling and analysis of whole-genome sequence of clinical Klebsiella pneumoniae isolates. Antibiotics, 9(5), 261.
Stahlhut, S. G., Struve, C., Krogfelt, K. A., & Reisner, A. (2012). Biofilm formation of Klebsiella pneumoniae on urethral catheters requires either type 1 or type 3 fimbriae. FEMS Immunology & Medical Microbiology, 65(2), 350-359.
Standiford, L. R., Standiford, T. J., Newstead, M. J., Zeng, X., Ballinger, M. N., Kovach, M. A., Reka, A. K., & Bhan, U. (2012). TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia. American Journal of Physiology-Lung Cellular and Molecular Physiology, 302(5), L447-L454.
Struve, C., Bojer, M., & Krogfelt, K. A. (2009). Identification of a conserved chromosomal region encoding Klebsiella pneumoniae type 1 and type 3 fimbriae and assessment of the role of fimbriae in pathogenicity. Infection and immunity, 77(11), 5016-5024.
Struve, C., Roe, C. C., Stegger, M., Stahlhut, S. G., Hansen, D. S., Engelthaler, D. M., Andersen, P. S., Driebe, E. M., Keim, P., & Krogfelt, K. A. (2015). Mapping the evolution of hypervirulent Klebsiella pneumoniae. MBio, 6(4), e00630-00615.
Suay-García, B., & Pérez-Gracia, M. T. (2019). Present and future of carbapenem-resistant Enterobacteriaceae (CRE) infections. Antibiotics, 8(3), 122.
Tekeli, A., Dolapci, İ., Evren, E., Oguzman, E., & Karahan, Z. C. (2020). Characterization of Klebsiella pneumoniae coproducing KPC and NDM-1 carbapenemases from Turkey. Microbial Drug Resistance, 26(2), 118-125.
Terreni, M., Taccani, M., & Pregnolato, M. (2021). New antibiotics for multidrug-resistant bacterial strains: latest research developments and future perspectives. Molecules, 26(9), 2671.
Uddin, T. M., Chakraborty, A. J., Khusro, A., Zidan, B. R. M., Mitra, S., Emran, T. B., Dhama, K., Ripon, M. K. H., Gajdács, M., & Sahibzada, M. U. K. (2021). Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects. Journal of Infection and Public Health, 14(12), 1750-1766.
Virolle, C., Goldlust, K., Djermoun, S., Bigot, S., & Lesterlin, C. (2020). Plasmid transfer by conjugation in Gram-negative bacteria: from the cellular to the community level. Genes, 11(11), 1239.
Wilkins, M., Hall-Stoodley, L., Allan, R. N., & Faust, S. N. (2014). New approaches to the treatment of biofilm-related infections. Journal of Infection, 69, S47-S52.
Wyres, K. L., Lam, M. M., & Holt, K. E. (2020). Population genomics of Klebsiella pneumoniae. Nature Reviews Microbiology, 18(6), 344-359.
Yap, P. S.-X., Cheng, W.-H., Chang, S.-K., Lim, S.-H. E., & Lai, K.-S. (2022). MgrB Mutations and Altered Cell Permeability in Colistin Resistance in Klebsiella pneumoniae. Cells, 11(19), 2995.
Zheng, J.-x., Lin, Z.-w., Sun, X., Lin, W.-h., Chen, Z., Wu, Y., Qi, G.-b., Deng, Q.-w., Qu, D., & Yu, Z.-j. (2018). Overexpression of OqxAB and MacAB efflux pumps contributes to eravacycline resistance and heteroresistance in clinical isolates of Klebsiella pneumoniae. Emerging microbes & infections, 7(1), 1-11.
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