Enterococcus faecalis and pathogenic streptococci inactivate daptomycin by releasing phospholipids.
Elizabeth V K Ledger1, Vera Pader1, Andrew M Edwards1
1MRC Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Rd, London, SW7 2AZ, UK.
Gram-positive bacteria, including Enterococcus faecalis, can inactivate the antibiotic daptomycin by releasing membrane phospholipids. This defense mechanism may explain why daptomycin treatment sometimes fails for certain bacterial infections.
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.
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