PT  - JOURNAL ARTICLE
AU  - Elizabeth V. K. Ledger
AU  - Vera Pader
AU  - Andrew M. Edwards
TI  - <em>Enterococcus faecalis and pathogenic streptococci</em> inactivate daptomycin by releasing phospholipids
AID  - 10.1101/149971
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 149971
4099  - http://biorxiv.org/content/early/2017/06/14/149971.short
4100  - http://biorxiv.org/content/early/2017/06/14/149971.full
AB  - Daptomycin is a lipopeptide antibiotic with activity against Gram-positive bacteria. We have shown 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 phospholipid 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.