Andrew M. Edwards PhD
Lecturer in Molecular Bacteriology
MRC Centre for Molecular Bacteriology and Infection
Imperial College London
Daptomycin is a bactericidal antibiotic of last resort for serious drug-resistant staphylococcal infections. Although resistance is rare, treatment failure occurs in up to 30% cases. We have discovered that the frequent loss of the Agr quorum-sensing system in clinical isolates enables S. aureus to survive during daptomycin treatment. Agr-defective mutants release membrane phospholipids in response to daptomycin, which act as decoys by binding and inactivating the antibiotic. Wild-type bacteria also release phospholipid in response to daptomycin, but the Agr-triggered secretion of phenol soluble modulins prevents inactivation of the antibiotic. On-going work seeks to develop new therapeutic strategies that prevent phospholipid release in vivo and provide a clinically-applicable mechanism by which daptomycin therapeutic outcomes can be enhanced.