Daptomycin nonsusceptibility in Staphylococcus aureus with reduced vancomycin susceptibility is independent of

Satish K Pillai1, Howard S Gold, George Sakoulas

  • 1Department of Infectious Disease, Cleveland Clinic Foundation, Mailstop S32, Cleveland, OH 44195, USA. pillais@ccf.org

Insights

Mutations in mprF are not always responsible for decreased susceptibility to daptomycin in Staphylococcus aureus. Some isolates develop daptomycin nonsusceptibility and vancomycin heteroresistance without mprF mutations, even without prior drug exposure.

Area of Science:

  • Microbiology
  • Antimicrobial Resistance
  • Molecular Biology

Background:

  • Previous research linked mutations in mprF to reduced daptomycin susceptibility in Staphylococcus aureus.
  • A connection between vancomycin-intermediate S. aureus and daptomycin nonsusceptibility has been recently observed.

Purpose of the Study:

  • To investigate the genetic basis of daptomycin nonsusceptibility in clinical Staphylococcus aureus isolates that developed vancomycin heteroresistance.
  • To determine if mutations in the mprF gene are present in S. aureus isolates exhibiting daptomycin nonsusceptibility without prior drug exposure.

Main Methods:

  • Analysis of three clinical Staphylococcus aureus isolates.
  • Genomic sequencing to identify mutations in the mprF gene.
  • Phenotypic testing for vancomycin heteroresistance and daptomycin susceptibility.

Main Results:

  • The three clinical S. aureus isolates exhibited both vancomycin heteroresistance and daptomycin nonsusceptibility.
  • Despite the observed nonsusceptibility, no mutations leading to amino acid substitutions in the MprF protein were detected in these isolates.
  • This occurred in isolates with no prior exposure to daptomycin.

Conclusions:

  • The mprF gene is not the sole factor contributing to daptomycin nonsusceptibility in Staphylococcus aureus.
  • Alternative mechanisms may be involved in the development of daptomycin nonsusceptibility and vancomycin heteroresistance in S. aureus.
  • Further research is needed to elucidate the pathways driving resistance in the absence of mprF mutations.

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