期刊
VIRULENCE
卷 6, 期 2, 页码 127-131出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21505594.2015.1011532
关键词
bacterial persistence; Galleria mellonella; mprF; S. aureus; walK
资金
- Australian Postgraduate Award
- Monash University Postgraduate Publication Award
- Australian National Health and Medical Research Council [APP1047916, APP1047918]
- National Institutes of Health [P01 AI083214]
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.
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