Impact of daptomycin resistance on Staphylococcus aureus virulence

Virulence. 2015;6(2):127-31. doi: 10.1080/21505594.2015.1011532.


Daptomycin resistance (DAP(R)) in Staphylococcus aureus is associated with mutations in genes that are also implicated in staphylococcal pathogenesis. Using a laboratory-derived series of DAP exposed strains, we showed a relationship between increasing DAP MIC and reduced virulence in a Galleria mellonella infection model. Point mutations in walK and rpoC led to cumulative reductions in virulence and simultaneous increases in DAP MIC. A point mutation to mprF did not impact on S.aureus virulence; however deletion of mprF led to virulence attenuation and hyper-susceptibility to DAP. To validate our findings in G. mellonella, we confirmed the attenuated virulence of select isolates from the laboratory-derived series using a murine septicaemia model. As a corollary, we showed significant virulence reductions for clinically-derived DAP(R) isolates compared to their isogenic, DAP-susceptible progenitors (DAP(S)). Intriguingly, each clinical DAP(R) isolate was persistent in vivo. Taken together, it appears the genetic correlates underlying daptomycin resistance in S. aureus also alter pathogenicity.

Keywords: Galleria mellonella; S. aureus; bacterial persistence; mprF; walK.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / metabolism
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Daptomycin / pharmacology*
  • Drug Resistance, Multiple, Bacterial
  • Genotype
  • Larva / microbiology
  • Microbial Sensitivity Tests
  • Moths / microbiology
  • Phenotype
  • Point Mutation
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / pathogenicity*
  • Virulence


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Aminoacyltransferases
  • mprF protein, Staphylococcus aureus
  • Daptomycin