Drivers and Barriers: Understanding AMR Gene Transfer in MRSA Biofilms and Colonisation (360G-Wellcome-338375_Z_25_Z)

Antimicrobial resistance (AMR) is one of the greatest challenges to global health. Among resistant pathogens, methicillin-resistant Staphylococcus aureus (MRSA) remains a leading cause of AMR-related deaths and a persistent threat in hospitals, communities, and livestock. MRSA evolves into multidrug- resistant (MDR) clones by rapidly acquiring genes through horizontal gene transfer (HGT), yet how these genetic exchanges are regulated, restricted, and shaped by environmental cues is poorly understood. This project will investigate the genetic barriers and drivers of HGT in two clinically relevant settings: biofilms and host colonisation. HGT in S. aureus has been mainly attributed to bacteriophage transduction, while transformation has long been considered irrelevant. My doctoral research challenged this assumption by demonstrating that the methicillin resistance element SCCmec can be acquired in biofilms via transformation. Building on this discovery and my collaborators’ expertise in HGT barriers and bacterial colonisation models of human skin, I will address three questions: (1) what barriers limit DNA uptake in MRSA biofilms; (2) how do transformation and transduction interact, and (3) how is HGT modulated during MRSA colonisation. By uncovering how MDR-MRSA clones emerge and persist, this research will inform infection control and One Health strategies while providing new opportunities for therapeutic and diagnostic innovation.