ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance

ESBL-Producing <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> Exhibit Divergent Paths During In-Human Evolution Towards Carbapenem Resistance

Treatment of infections caused by ESBL-producing <i>Escherichia coli</i> (EC) and <i>Klebsiella pneumoniae</i> (KP) with carbapenem antibiotics can lead to the development of carbapenem resistance over time through the acquisition of porin mutations and plasmids bearing <i...

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Bibliographic Details
Main Authors: Michelle Chioma Kalu, Akanksha Acharya, Peter Jorth, Annie Wong-Beringer
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Microorganisms
Subjects:
carbapenem resistance
ESBL-producing <i>Enterobacterales</i>
genetic evolution
CRISPR-Cas
Online Access:https://www.mdpi.com/2076-2607/13/6/1387
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Summary:Treatment of infections caused by ESBL-producing <i>Escherichia coli</i> (EC) and <i>Klebsiella pneumoniae</i> (KP) with carbapenem antibiotics can lead to the development of carbapenem resistance over time through the acquisition of porin mutations and plasmids bearing <i>blaKPC</i>. However, the impact of genetic background and the presence of CRISPR-Cas systems on the evolutionary path towards carbapenem resistance in EC and KP has yet to be investigated. The in-human evolution following repeated carbapenem treatment among ESBL-producing <i>Escherichia coli</i> (EC) and <i>Klebsiella pneumoniae</i> (KP) clinical pairs (n = 45 pairs) was examined to determine the relationship between strain genetic background (MLST, CRISPR-Cas) and the evolved genetic mutations related to resistance, virulence, and metabolism by whole genome sequencing. ST131 and ST258 were predominant among seven distinct STs in EC (70%, 19/27) and 11 STs in KP (33%, 6/18), respectively. Complete CRISPR-Cas systems were present in 22% EC (6/27) and 27.8% (5/18) KP pairs, but none in strains belonging to ST131 or ST258; partial loss of CRISPR-Cas was associated with increased carbapenem resistance. Porin, virulence, and metabolism-related genetic mutations were present on the chromosome in both the EC and KP evolved strains, but their presence was differentially associated with the CRISPR-Cas system. Future research on the role of antibiotic exposure in the species-specific resistance evolution of the <i>Enterobacterales</i> could guide antimicrobial stewardship efforts.
ISSN:2076-2607

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