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Cefazolin and imipenem enhance AmpC expression and resistance in NagZ-dependent manner in Enterobacter cloacae

Xianggui Yang1, Zhenguo Wang2, Mingquan Liu3

  • 1Department of Laboratory Medicine, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China. yxg204@163.com.

BMC Microbiology
|November 28, 2022
PubMed
Abstract

Insights

Subinhibitory concentrations of cefazolin and imipenem can increase Enterobacter cloacae complex resistance by inducing AmpC expression via NagZ. Caution is advised when using these antibiotics, as they may worsen resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Enterobacter cloacae complex (ECC) is an opportunistic pathogen causing human infections.
  • ECC possesses inducible AmpC β-lactamase, conferring resistance to early-generation cephalosporins.
  • The impact of beta-lactam antibiotics on ECC resistance remains incompletely understood.

Purpose of the Study:

  • To investigate whether beta-lactam antibiotics enhance resistance in Enterobacter cloacae complex.
  • To elucidate the role of NagZ in the induction of AmpC expression and beta-lactam resistance.

Main Methods:

  • Exposure of Enterobacter cloacae (EC) to subinhibitory concentrations (SICs) of cefazolin (CFZ) and imipenem (IMP).
  • Analysis of AmpC expression levels in wild-type and nagZ knockout (ΔnagZ) EC strains.
  • Assessment of beta-lactam resistance in EC with altered NagZ expression.

Main Results:

  • SICs of CFZ and IMP induced AmpC expression and enhanced beta-lactam resistance in EC.
  • NagZ was identified as a critical mediator, as its absence abrogated AmpC induction and resistance.
  • Ectopic expression of NagZ restored CFZ- and IMP-induced AmpC expression and resistance.

Conclusions:

  • NagZ is essential for cefazolin and imipenem to promote AmpC expression and resistance in ECC.
  • The use of cefazolin and imipenem may exacerbate ECC resistance, warranting caution.
  • This study enhances understanding of resistance mechanisms within the Enterobacter cloacae complex.
Keywords:
AmpCCefazolinEnterobacter cloacae complexImipenemNagZ

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