Enterococcus faecalis and pathogenic streptococci inactivate daptomycin by releasing phospholipids

Area of Science:

• Microbiology
• Antibiotic Resistance
• Biochemistry

Background:

• Daptomycin is a lipopeptide antibiotic effective against Gram-positive bacteria.
• Previous research demonstrated Staphylococcus aureus releases membrane phospholipids to inactivate daptomycin.
• The prevalence of this defense mechanism in other pathogens remains unclear.

Purpose of the Study:

• To investigate if other pathogenic Gram-positive bacteria employ phospholipid release as a defense against daptomycin.
• To quantify phospholipid release and daptomycin inactivation in various bacterial species.

Main Methods:

• Incubation of Staphylococcus epidermidis, Streptococcus species, and Enterococcus faecalis with daptomycin.
• Measurement of phospholipid release and residual daptomycin activity.
• Inhibition of phospholipid release using platensimycin in Enterococcus faecalis.

Main Results:

• All tested bacteria released phospholipids in response to daptomycin, leading to partial antibiotic inactivation.
• Enterococcus faecalis exhibited the highest levels of phospholipid release and daptomycin inactivation.
• Platensimycin effectively inhibited daptomycin-induced phospholipid release in Enterococcus faecalis.

Conclusions:

• Several pathogenic Gram-positive bacteria, notably Enterococcus faecalis, possess a mechanism to inactivate daptomycin via phospholipid release.
• This phospholipid-mediated inactivation may contribute to daptomycin treatment failures in infections caused by these bacteria.