Harnessing Microbiome Constituents to Prevent Recurrent Pediatric Methicillin-Resistant Staphylococcus Aureus Infections

Key Words: Methicillin-resistant Staphylococcus Aureus (MRSA), Antibiotic Persistence, Antibiotic Resistance, Neonatal and Pediatric Microbiome

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent source of infections affecting premature newborns and critically-ill children. Even after initial successful treatment, over 50% of MRSA infections recur. While some of these recurrences can be attributed to repeated infections, they are also frequently linked to a subset of bacteria that respond to cues in an infection environment, which enable them to alter their physiology and survive antibiotic treatment. Once the course of antibiotic treatment is over, these “persisters” can resume cell division, leading to infection relapse. To make matters worse, repeated courses of antibiotics needed to resolve recurrent infections can select for MRSA mutants that have become more tolerant or resistant to existing antibiotics. MRSA routinely colonize the skin and the nose, where it can interact with other bacterial species in these sites. We predict that some of these bacteria can secrete molecules that act on MRSA and affect their antibiotic persistence. In this project, we will investigate how the secreted products from a bacterial species that colonizes neonates and children impact MRSA’s response to antibiotics prescribed for its associated infections. We will also explore how interactions between MRSA and a beneficial microbe as well as a pathogenic microbe from the neonatal/ pediatric microbiome affect MRSA’s ability to evolve following rounds of antibiotic treatment. Findings from our study will enhance our understanding of how the local infection environment and microbiota affect MRSA’s susceptibility to specific antibiotics, which can lead to better strategies to manage and treat bacterial infections. Our research can potentially lead to the discovery of new molecules that can work together with existing antibiotics to effectively cure recurrent MRSA infections and improve the well-being of some of the most vulnerable pediatric patients.