Molecular characteristics, fitness, and virulence of high-risk and non-high-risk clones of carbapenemase-producing Klebsiella pneumoniae

• Published in: Microbiology spectrum Vol. 12; no. 2; p. e0403622
• Main Authors: Örmälä-Tiznado, Anni-Maria, Allander, Lisa, Maatallah, Makaoui, Kabir, Muhammad Humaun, Brisse, Sylvain, Sandegren, Linus, Patpatia, Sheetal, Coorens, Maarten, Giske, Christian G
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 06.02.2024
• Subjects: Animals; Anti-Bacterial Agents - therapeutic use; antimicrobial resistance; Bacterial Proteins - genetics; beta-Lactamases - genetics; Clinical Microbiology; Clone Cells; competition; fitness; flow cytometry; Galleria mellonella; Klebsiella Infections - microbiology; Klebsiella pneumoniae; Klebsiella pneumoniae - genetics; Larva; Medicin och hälsovetenskap; Microbial Sensitivity Tests; Research Article; virulence; Virulence - genetics; Virulence Factors - genetics; virulence; antimicrobial resistance; fitness; competition; flow cytometry; Galleria mellonella; Klebsiella pneumoniae
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.04036-22

Extensively drug-resistant (XDR) inflict a notable burden on healthcare worldwide. Of specific concern are strains producing carbapenem-hydrolyzing enzymes, as the therapeutic options for these strains are still very limited. Specific sequence types of have been noted for their epidemic occurrence globally, but the mechanisms behind the success of specific clones remain unclear. Herein, we have characterized 20 high-risk clones (HiRCs) and 10 non-HiRCs of XDR , exploring factors connected to the epidemiological success of some clones. Isolates were subjected to core genome multilocus sequence typing analysis to determine the clonal relationships of the isolates and subsequently characterized with regard to features known to be linked to overall bacterial fitness and virulence. The genomes were analyzed for capsule types, O antigens, virulence factors, antimicrobial resistance genes, prophages, and CRISPR-Cas loci. growth experiments were conducted to retrieve proxies for absolute and relative fitness for 11 HiRC and 9 non-HiRC isolates selected based on the clonal groups they belonged to, and infections in a insect model were used to evaluate the virulence of the isolates . This study did not find evidence that virulence factors, prophages, CRISPR-Cas loci, or fitness measured alone would contribute to the global epidemiological success of specific clones of carbapenemase-producing XDR . However, this study did find the HiRC group to be more virulent than the non-HiRC group when measured in a model with . This suggests that the virulence and epidemiological success of certain clones of cannot be explained by individual traits investigated in this study and thus warrant further experiments in the future.IMPORTANCEHerein, we explored potential explanations for the successfulness of some epidemic or high-risk clones of carbapenemase-producing . We found differences in mortality in a larva model but found no clear genomic differences in known virulence markers. Most of the research on virulence in has been focused on hypervirulent strains, but here, we try to understand differences within the group of highly resistant strains. The results from the larva virulence model could be used to design experiments in higher animals. Moreover, the data could provide further support to a differentiated infection control approach against extensively drug-resistant strains, based on their classification as high-risk clones.