Ning Dong
Ruichao Li
Yichyi Lai- 1Department of Medical Microbiology, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, China
- 2Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Soochow University, Suzhou, China
- 3Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- 4Institute of Comparative Medicine, Yangzhou University, Yangzhou, China
- 5Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, China
- 6Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, China
Editorial on the Research Topic
Klebsiella pneumoniae: Antimicrobial resistance, virulence and therapeutic strategies
Klebsiella pneumoniae is a member of the ESKAPE organisms which include 6 well-known highly virulent and antimicrobial-resistant clinical pathogens (Dong et al., 2022). K. pneumoniae has gained the ability to acquire external genetic materials that enable it to undergo constant evolution (Russo and Marr, 2019). The pathotypes reported to be associated with infections included classical (cKP) and hypervirulent K. pneumoniae (hvKP), with the former known for the capacity to acquire resistance to a wide range of antibiotics and the latter exhibiting high pathogenicity and leading to high mortality in otherwise immunocompromised hosts (Paczosa and Mecsas, 2016). To date, more than 100 distinct acquired antimicrobial resistance genes have been identified in K. pneumoniae (Wyres and Holt, 2016). Furthermore, apart from the well-established factors that help K. pneumoniae escape the innate immune mechanisms of the host, new virulence factors have been discovered (Walker et al., 2019; Walker et al., 2020; Gomes et al., 2021). Continuous effort is necessary to better understand this ‘superbug’ and help design feasible approaches to eradicate or halt its further evolution. As a step towards countering the threat of K. pneumoniae, our Research Topic brings a collection of seven selected articles exploring its molecular epidemiology, antimicrobial resistance, and pathogenesis.
K. pneumoniae is a common pathogen of community-acquired pneumonia (CAP) in Asian countries (Song et al., 2008). Chen et al. revisited the burden of K. pneumoniae bacteremic pneumonia (KPBP) and determined the risk factors associated with 28-day mortality by analyzing data from 150 patients with KPBP in Taiwan from 2014-2020. A remarkably high 28-day mortality was observed in all patients. hvKP was more prevalent in CAP than in nosocomial pneumonia, yet carbapenem-resistant K. pneumoniae (CRKP) was more prevalent in nosocomial pneumonia than in CAP. Nosocomial pneumonia, Severe Organ Failure Assessment core, and lack of appropriate definitive treatment were positive predictors for 28-day mortality among patients with KPBP. The results suggested host factors, disease severity, and timely effective therapy could affect the treatment outcomes of patients with KPBP.
Information regarding hvKp infections in pediatric patients remains limited. Du et al. characterized K. pneumoniae strains from a children’s hospital in Shanghai during 2019-2020. They found KPC-2-producing KL47-ST11 hypervirulence genes-positive (hgKp) increased dramatically from 5.3% in 2019 to 67.6% in 2020, suggesting genetic convergence of virulence and carbapenem-resistance in K. pneumoniae is increasing among children. hgKp could be classified into hvKP (32.5%) and hgKp-low virulence strains (67.5%). hvKp infections in children were mostly hospital-associated and commonly involved severe pneumonia. In hvKp, diverse genetic clones were observed and K1-ST23 and K2-ST25 were the dominant clones. These findings suggested the dramatic spread of hvKP in children.
K. pneumoniae strains resistant to the last-resort antibiotic, ceftazidime-avibactam (CZA) have been increasingly reported recently. Bongiorno et al. characterized 16 CZA-resistant KPC-producing K. pneumoniae strains from Italy. The strains were from three major clones, ST101, ST307, and ST512. All strains carried blaKPC. Most strains carried blaKPC-3 (62.5%), and other strains carried other variants (blaKPC-28, blaKPC-31, blaKPC-34, and blaKPC-50). Besides, frameshift mutations on OmpK35 and OmpK36 were observed in 15/16 strains. These results suggested CZA resistance in K. pneumoniae arises through both the spread of epidemic clones and the horizontal dissemination of blaKPC variants.
Gastrointestinal carriage is a major reservoir of K. pneumoniae infection (Gorrie et al., 2017). Migliorini et al. investigated the mechanisms associated with the transition from carriage to infection by K. pneumoniae isolates carrying blaKPC by characterizing KPC-producing strains isolated within a 10-year period. They showed the presence of resistance and virulence mechanisms were not associated with progression from colonization to infection, while intestinal colonization by carbapenem-resistant Enterobacteriaceae and, more specifically, the load of gastrointestinal carriage emerged as an important determinant of infection.
ST11 is reported to be the dominant CRKP clone in China (Qi et al., 2011). TMexCD1-TOprJ1 is the first plasmid-borne RND-type tigecycline resistance determinant reported recently (Lv et al., 2020). Li et al. characterize two clinical ST11 CRKP strains co-harboring the gene cluster tmexCD2-toprJ2 and the metallo-β-lactamase gene blaNDM-1 on the IncFIB(Mar)-like/HI1B-like group of hybrid plasmids. One of the two strains also carried blaKPC-2 on an IncN/U plasmid. Dissemination of tmexCD-toprJ in clinical high-risk CRKP clones may have exacerbated the antimicrobial resistance crisis.
The Klebsiella genus comprises a wide diversity of species apart from K. pneumoniae (Dong et al., 2022). Drug-resistant K. michiganensis strains have been increasingly reported recently. Li et al. reported the first clinical multidrug-resistant K. michiganensis strain co-harboring two blaSIM-1, one mcr-9.2, and 23 other resistance genes. They further comprehensively investigated the population structure and antibiotic-resistance genes of K. michiganensis by studying 275 publicly available genomes. Two major clades were identified, with the most popular sequence type ST29 being located in Clade 1, while other common STs (such as ST50, ST27, and ST43) in Clade 2. 25.5% K. michiganensis harbored at least one carbapenemase gene. ST27 isolates possess the most drug-resistance gene number among all the STs. The results of this study improved the understanding of K. michiganensis.
Infection caused by cKP represents a significant challenge due to its rising antibiotic resistance. Mackel et al. dissected the adaptive immune responses elicited by live cKp infection and investigated how these responses protected the host from reinfection by using a lung inoculation plus challenge model. They found circulating antibody responses alone were not sufficient to mediate protection against cKP, yet either of the major T cell subsets alone (γδ or αβ) was sufficient to mediate protection; also, the circulating T cell pool was not required for the protective phenotype. These findings altogether demonstrated the imperative contribution of T cells to protective immunity against cKP which would guide further inquiries into host effector responses required to control cKP infection.
The articles presented in this collection provide a valuable addition to the understanding of the notorious pathogen, K. pneumoniae. We hope these contributions will help investigators in their continuous scientific pursuit to tackle issues around the antimicrobial resistance and hypervirulence of this superbug. Related fields such as accurate and rapid pathogen detection and the design of optimal treatment regimens warrant further attention.
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Funding
This study was funded by the Natural Science Foundation of Jiangsu Province (No. BK20220493) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Acknowledgments
The editors would like to thank all the authors of each manuscript submitted to this Research Topic and thank all reviewers for their intelligence inputs.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
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Gomes, A.É.I., Pacheco, T., Santos, C. D. S. D., Pereira, J. A., Ribeiro, M. L., Darrieux, M., et al. (2021). Functional insights from KpfR, a new transcriptional regulator of fimbrial expression that is crucial for klebsiella pneumoniae pathogenicity. Front. Microbiol. 11, 601921. doi: 10.3389/fmicb.2020.601921
Gorrie, C. L., Mirčeta, M., Wick, R. R., Edwards, D. J., Thomson, N. R., Strugnell, R. A., et al. (2017). Gastrointestinal carriage is a major reservoir of klebsiella pneumoniae infection in intensive care patients. Clin. Infect. Dis. 65, 208–215. doi: 10.1093/cid/cix270
Lv, L., Wan, M., Wang, C., Gao, X., Yang, Q., Partridge, S. R., et al. (2020). Emergence of a plasmid-encoded resistance-Nodulation-Division efflux pump conferring resistance to multiple drugs, including tigecycline, in klebsiella pneumoniae. mBio 11, e02930-19. doi: 10.1128/mBio.02930-19
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Keywords: klebsiella pneumoniae, antimicrobial resistance (AMR), virulence factors, pathogenesis, host-pathogen interaction, molecular epidemiology, genomic analysis
Citation: Dong N, Li R and Lai Y (2022) Editorial: Klebsiella pneumoniae: Antimicrobial resistance, virulence and therapeutic strategies. Front. Cell. Infect. Microbiol. 12:1108817. doi: 10.3389/fcimb.2022.1108817
Received: 26 November 2022; Accepted: 01 December 2022;
Published: 23 December 2022.
Edited and Reviewed by:
Max Maurin, Université Grenoble Alpes, FranceCopyright © 2022 Dong, Li and Lai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ning Dong, dong.ning@connect.polyu.hk