Winner of the JAM Talks 16/17 - Vera Padar

The Junior Awards in Microbiology (JAM) Talks are a monthly junior seminar series aimed at integrating and connecting young researchers around the world.  

Each month a new junior researcher is invited to present their work in a relaxed, friendly environment in an exciting and engaging way.  This series of talks are sponsored by the Institute of Microbiology and Infection (IMI) and the Microbiology Society. Currently JAM Talks 2017 are hosted by the IMI at the University of Birmingham.  

Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids

Daptomycin is a bactericidal antibiotic of last resort for serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Although resistance is rare, treatment failure can occur in >20% of cases and so there is a pressing need to identify and mitigate factors that contribute to poor therapeutic outcomes. Here, we show that loss of the Agr quorum-sensing system, which frequently occurs in clinical isolates, enhances S. aureus survival during daptomycin treatment. Wild-type S. aureus was killed rapidly by daptomycin but Agr-defective mutants survived antibiotic exposure by releasing membrane phospholipid, which bound and inactivated the antibiotic. Although wild-type bacteria also released phospholipid in response to daptomycin, Agr-triggered secretion of small cytolytic toxins, known as phenol soluble modulins, prevented antibiotic inactivation. Phospholipid shedding by S. aureus occurred via an active process and was inhibited by the β-lactam antibiotic oxacillin and next generation phospholipid biosynthesis inhibitors, which slowed inactivation of daptomycin and enhanced bacterial killing. In conclusion, S. aureus possesses a transient defence mechanism that protects against daptomycin, which can be compromised by Agr-triggered toxin production or an existing therapeutic antibiotic.