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Evolution of Daptomycin Resistance in Coagulase-Negative Staphylococci Involves Mutations of the Essential

Jhih-Hang Jiang1, Carina Dexter1, David R Cameron1

  • 1Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia.

Antimicrobial Agents and Chemotherapy
|January 9, 2019
PubMed

Insights

Antimicrobial resistance in coagulase-negative staphylococci (CoNS) is increasing. This study found that mutations in the walKR system drive daptomycin resistance in CoNS, differing from Staphylococcus aureus mechanisms.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Coagulase-negative staphylococci (CoNS) are significant causes of healthcare-associated infections.
  • Emerging antimicrobial resistance in CoNS complicates treatment options.
  • Daptomycin resistance in CoNS is a growing concern.

Purpose of the Study:

  • To investigate the prevalence and mechanisms of daptomycin resistance in clinical CoNS strains.
  • To compare daptomycin resistance mechanisms in CoNS with those in Staphylococcus aureus.
  • To identify genetic factors contributing to daptomycin resistance in CoNS.

Main Methods:

  • Surveillance of antimicrobial resistance in clinical CoNS isolates over four years.
  • In vitro generation of daptomycin-resistant (DAP-R) CoNS mutants from susceptible strains.
  • Whole-genome sequencing and targeted gene analysis (PCR, sequencing) of DAP-R strains.
  • Functional validation by recreating specific mutations in Staphylococcus epidermidis.

Main Results:

  • A significant increase in daptomycin resistance was observed in clinical CoNS strains, particularly Staphylococcus capitis.
  • Daptomycin-resistant CoNS mutants showed compromised biofilm formation but not altered cell surface charge.
  • Whole-genome sequencing identified single nucleotide polymorphisms (SNPs) in the essential two-component system walKR.
  • Seven nonsynonymous mutations in walK or walR were found in clinical DAP-R isolates.
  • Recreating a walK SNP in S. epidermidis reduced susceptibility to daptomycin and vancomycin.

Conclusions:

  • The walKR two-component system is a key factor in the development of daptomycin resistance in CoNS.
  • Mechanisms of daptomycin resistance in CoNS may differ from those in Staphylococcus aureus.
  • WalKR mutations represent a shared mechanism of antibiotic resistance across staphylococcal species.
  • CoNS are significant contributors to the evolving landscape of daptomycin resistance.
Keywords:
coagulase-negative staphylococcidaptomycinwalKR

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