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Acid-dependent beta-lactam resistance in Klebsiella pneumoniae is mediated by paralogous class B PBPs and the class A PBP, PBP1b

ABSTRACT: Klebsiella pneumoniae is a leading cause of global deaths due to antibiotic resistance. Of particular concern, is the rapid expansion within K. pneumoniae lineages of resistance to beta-lactams, the most prescribed class of antibiotics. Additionally, the environmental factors that influence pathogen physiology and, subsequently, antibiotic resistance remain poorly understood. Here we demonstrate that physiologically-relevant drops in culture medium pH result in increased antibiotic resistance particularly towards beta-lactams that inhibit cell division. We identified two genes that contribute to acid-dependent beta-lactam resistance, the class A PBP, PBP1b, and the paralogous class B PBP, PBP3PARA. Loss of either gene increases K. pneumoniae susceptibility to beta-lactams at low pH. Our data suggests that functional redundancy among cell wall synthesis enzymes allows for specialization and ensures that cell wall synthesis occurs robustly across a range of pH conditions.

ORGANISM(S): Escherichia coli str. K-12 substr. MG1655 Klebsiella pneumoniae

PROVIDER: GSE291667 | GEO | 2025/03/17

REPOSITORIES: GEO

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