Impact of daptomycin resistance on Staphylococcus aureus virulence.

Abstract:

: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.

journal_name

Virulence

journal_title

Virulence

authors

Cameron DR,Mortin LI,Rubio A,Mylonakis E,Moellering RC Jr,Eliopoulos GM,Peleg AY

doi

10.1080/21505594.2015.1011532

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

127-31

issue

2

eissn

2150-5594

issn

2150-5608

journal_volume

6

pub_type

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