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Scientific article
Open access
English

Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae

Published inMicrobiology spectrum, vol. 10, no. 1, e01766-21
Publication date2022-02-23
First online date2022-02-16
Abstract

In the major human pathogen Klebsiella pneumoniae, MgrB inactivation by disruptive insertion sequence (IS) elements and mutations leading to early termination are known to play an important role in polymyxin resistance. In this study, we examined a collection of invasive blaKPC-2-producing K. pneumoniae isolates belonging to the high-risk clone sequence type 258 (ST258) displaying high rates of resistance to many antimicrobials, including polymyxins. We identified a deleterious substitution (W20S) in MgrB and confirmed by genetic complementation analysis that this variant was inactive, leading to increased polymyxin B and colistin MICs.

IMPORTANCE Carbapenem-resistant Gram-negative bacteria are designated critical pathogens by the World Health Organization. Polymyxins (i.e., polymyxin B and colistin) are last-resort antibiotics and particularly useful against these multidrug-resistant bacteria. In Klebsiella pneumoniae, the inactivation of MgrB, a negative regulator of PhoPQ, was shown to be the major pathway leading to colistin resistance. While gene disruption by insertion sequence (IS) elements and mutations leading to early termination (stop codons) are frequent, deleterious mutations are not observed frequently and have not been characterized. Here, we identified a deleterious substitution (W20S) in MgrB among a collection of bloodstream infection, blaKPC-2-producing K. pneumoniae sequence type 258 (ST258) isolates, displaying high rates of resistance to polymyxins and associated with a high mortality rate. The dissemination of such a MgrB-W20S mutation leading to polymyxin resistance within the ST258 high-risk clone background is problematic and thus warrants particular attention.

eng
Keywords
  • Enterobacterales
  • KPC
  • Colistin
  • Multidrug resistance
  • Amino Acid Substitution
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Resistance, Bacterial
  • Humans
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / metabolism
  • Microbial Sensitivity Tests
  • Mutation, Missense
  • Polymyxin B / pharmacology
  • Beta-Lactamases / genetics
  • Beta-Lactamases / metabolism
Funding
Citation (ISO format)
ROCH, Mélanie et al. Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in <i>Klebsiella pneumoniae</i>. In: Microbiology spectrum, 2022, vol. 10, n° 1, p. e01766–21. doi: 10.1128/spectrum.01766-21

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