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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.

Enterococcus faecalis and pathogenic streptococci inactivate daptomycin by releasing phospholipids