Inactivation of mrcA gene derepresses the basal-level expression of L1 and L2 β-lactamases in Stenotrophomonas maltophilia

J Antimicrob Chemother. 2011 Sep;66(9):2033-7. doi: 10.1093/jac/dkr276. Epub 2011 Jun 30.

Abstract

Objectives: To characterize the relationship between inactivation of the mrcA gene and β-lactamase expression and β-lactams resistance in Stenotrophomonas maltophilia KJ and to investigate the involvement of ampR, ampN-ampG, ampD(I) and creBC in this.

Methods: The mrcA deletion mutant KJΔmrcA was constructed to investigate the role of this putative penicillin-binding protein 1a (PBP1a) in β-lactamase expression and β-lactam resistance. The ΔampR, ΔampNG, ΔampDI and ΔcreBC alleles were introduced into KJΔmrcA, and KJΔDIΔBC and KJΔDIΔmrcAΔBC were also constructed for comparison. All the mutants and their corresponding parent strains were assayed for β-lactamase activities and MICs of β-lactams.

Results: Inactivation of mrcA caused basal L1/L2 β-lactamase production to increase by ∼100-fold, but made little difference to cefuroxime-induced β-lactamase activity and the MICs of β-lactams. The ΔmrcA-derived basal β-lactamase hyperproduction was ampR and ampN-ampG dependent. Simultaneous inactivation of ampD(I) and mrcA did not augment β-lactamase production over and above that seen in an ampD(I) mutant alone. Furthermore, we could find no evidence for a role of the creBC two-component regulatory system in β-lactamase hyperproduction in a ΔampD(I) or ΔmrcA background.

Conclusions: Inactivation of mrcA, predicted to encode PBP1a, causes basal L1/L2 β-lactamase hyperproduction in S. maltophilia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • DNA Primers
  • Enzyme Induction / drug effects
  • Enzyme Induction / genetics
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Genes, Bacterial / genetics*
  • Lactams / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation / genetics
  • Plasmids / genetics
  • Regulon
  • Stenotrophomonas maltophilia / drug effects
  • Stenotrophomonas maltophilia / genetics*
  • Stenotrophomonas maltophilia / metabolism*
  • beta-Lactamases / biosynthesis*
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • DNA Primers
  • Lactams
  • beta-lactamase L1
  • beta-lactamase L2
  • beta-Lactamases