MurAA is required for intrinsic cephalosporin resistance of Enterococcus faecalis

Dušanka Vesić1, Christopher J Kristich

  • 1Department of Microbiology and Molecular Genetics, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Insights

Enterococcus faecalis intrinsic cephalosporin resistance involves MurAA, an enzyme in peptidoglycan synthesis. Disrupting murAA increases susceptibility to cephalosporins like ceftriaxone.

Area of Science:

  • Microbiology
  • Bacterial cell wall biosynthesis
  • Antibiotic resistance mechanisms

Background:

  • Enterococcus faecalis exhibits intrinsic resistance to cephalosporins, crucial antibiotics targeting bacterial cell wall synthesis.
  • The precise molecular mechanisms underlying this intrinsic resistance remain incompletely understood.

Purpose of the Study:

  • To identify genetic factors contributing to Enterococcus faecalis's intrinsic cephalosporin resistance.
  • To elucidate the specific role of MurAA in cephalosporin resistance.

Main Methods:

  • Screening of a transposon mutant library in E. faecalis for increased susceptibility to ceftriaxone.
  • In-frame deletion mutagenesis of murAA and its homolog murAB.
  • Assessing cephalosporin resistance in wild-type and mutant strains, including those lacking the IreK kinase.

Main Results:

  • A transposon mutant with disruption in murAA displayed heightened susceptibility to ceftriaxone.
  • Deletion of murAA, but not murAB, significantly increased cephalosporin susceptibility.
  • Overexpression of MurAA enhanced cephalosporin resistance in an IreK-deficient mutant, indicating MurAA's catalytic activity is necessary but not sufficient.

Conclusions:

  • MurAA and MurAB play distinct roles in E. faecalis physiology.
  • MurAA possesses a unique function that contributes to the intrinsic resistance of E. faecalis to cephalosporins.

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