@article{a639e9c0d3d64450afe39f07dc82525f,
title = "Impact of daptomycin resistance on Staphylococcus aureus virulence",
abstract = "Daptomycin resistance (DAPR) 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 DAPRisolates compared to their isogenic, DAP-susceptible progenitors (DAPS). Intriguingly, each clinical DAPRisolate was persistent in vivo. Taken together, it appears the genetic correlates underlying daptomycin resistance in S. aureus also alter pathogenicity.",
keywords = "Bacterial persistence, Galleria mellonella, MprF, S. aureus, Walk",
author = "Cameron, {David R.} and Mortin, {Lawrence I.} and Aileen Rubio and Eleftherios Mylonakis and Moellering, {Robert C.} and Eliopoulos, {George M.} and Peleg, {Anton Y.}",
note = "Funding Information: D.R.C was funded by an Australian Postgraduate Award and a Monash University Postgraduate Publication Award. A.Y.P was funded by an Australian National Health and Medical Research Council R.D. Wright Biomedical Fellowship (APP1047916) and Project Grant (APP1047918). E. M was supported by National Institutes of Health grant P01 AI083214. Funding Information: A.Y.P has been to one advisory board meeting for Ortho-McNeil-Janssen and AstraZeneca, and has received a speaker{\textquoteright}s honorarium from AstraZeneca for one presentation. G.M.E. has served on Scientific Advisory Boards for Cubist, Bayer Schering, Johnson & Johnson Pharmaceutical Research and development, Novartis, Pfizer, Shionogi, Theravance; he has had research training support from Cubist, research contracts from Novexel, Pfizer and Theravance, and speaking honoraria from Novartis. He serves on the Board of Directors of the National Foundation for Infectious Diseases. R.C.M. served as a consultant to Cubist, Forest, Merck, Novartis, Ortho, Johnston and Johnston, Pfizer, Theravance, and Wyeth. E. M received grant support and served on the advisory board for Astellas Pharma and received grant support from T2 Biosystems. L.I.M and A.R. are scientists working for Cubist Pharmaceuticals. All other authors have no conflicts of interest. Publisher Copyright: {\textcopyright} 2015 Taylor & Francis Group, LLC.",
year = "2015",
month = apr,
day = "1",
doi = "10.1080/21505594.2015.1011532",
language = "English (US)",
volume = "6",
pages = "127--131",
journal = "Virulence",
issn = "2150-5594",
publisher = "Landes Bioscience",
number = "2",
}