Daptomycin is a lipopeptide antibiotic with activity against Gram-positive bacteria. We showed previously that Staphylococcus
aureus can survive daptomycin exposure by releasing membrane phospholipids that inactivate the antibiotic. To determine
whether other pathogens possess this defence mechanism, phospholipid release and daptomycin activity were measured
after incubation of Staphylococcus epidermidis, group A or B streptococci, Streptococcus gordonii or Enterococcus faecalis with
the antibiotic. All bacteria released phospholipids in response to daptomycin, which resulted in at least partial inactivation of
the antibiotic. However, E. faecalis showed the highest levels of lipid release and daptomycin inactivation. As shown
previously for S. aureus, phospholipid release by E. faecalis was inhibited by the lipid biosynthesis inhibitor platensimycin. In
conclusion, several pathogenic Gram-positive bacteria, including E. faecalis, inactivate daptomycin by releasing phospholipids,
which may contribute to the failure of daptomycin to resolve infections caused by these pathogens.