Impact of daptomycin resistance on Staphylococcus aureus virulence

David R Cameron1, Lawrence I Mortin, Aileen Rubio

  • 1a Department of Microbiology ; School of Biomedical Sciences; Monash University ; Melbourne , Australia.

Virulence
|April 2, 2015
PubMed

Insights

Mutations causing daptomycin resistance (DAP(R)) in Staphylococcus aureus also reduce its virulence. This study investigated the link between DAP(R) genetic changes and pathogenicity in infection models.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Genetics

Background:

  • Daptomycin resistance (DAP(R)) in Staphylococcus aureus is a growing clinical concern.
  • Mutations conferring DAP(R) are often found in genes linked to bacterial pathogenesis.

Purpose of the Study:

  • To investigate the relationship between genetic mutations causing DAP(R) and Staphylococcus aureus virulence.
  • To determine if DAP(R) mutations impact pathogenicity in vivo.

Main Methods:

  • Laboratory-evolved DAP-resistant Staphylococcus aureus strains were generated.
  • Virulence was assessed using Galleria mellonella and murine infection models.
  • Genetic mutations (walK, rpoC, mprF) and their effect on DAP minimum inhibitory concentration (MIC) and virulence were analyzed.

Main Results:

  • Increasing DAP MIC correlated with reduced virulence in Galleria mellonella.
  • Specific mutations in walK and rpoC cumulatively decreased virulence and increased DAP MIC.
  • mprF deletion attenuated virulence and increased susceptibility to DAP.
  • Clinical DAP(R) isolates showed reduced virulence compared to susceptible counterparts and were persistent in vivo.

Conclusions:

  • Genetic determinants of daptomycin resistance in Staphylococcus aureus significantly impact bacterial pathogenicity.
  • Daptomycin resistance mechanisms may involve trade-offs with virulence, but clinical isolates can remain persistent.
  • Understanding these genetic alterations is crucial for managing Staphylococcus aureus infections.

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