Daptomycin Resistance in Enterococcus faecium Can Be Delayed by Disruption of the LiaFSR Stress Response Pathway

LiaFSR signaling plays a major role in mediating daptomycin (DAP) resistance in enterococci, and the lack of a functional LiaFSR pathway leads to DAP hypersusceptibility. Using in vitro experimental evolution, we evaluated how Enterococcus faecium with a liaR response regulator gene deletion evolved DAP resistance. We found that knocking out LiaFSR signaling significantly delayed the onset of resistance, but resistance could emerge eventually through various alternate mechanisms that were influenced by the environment.