Genomic and experimental investigation of inter-bacterial competitive mechanisms and protein secretion systems in clinical isolates of Serratia marcescens (360G-Wellcome-109118_Z_15_A)

Research into bacterial pathogenesis has long focused on ‘classical’ anti-host virulence factors. However given the current appreciation of the polymicrobial nature of infections, inter-bacterial competition mechanisms should also contribute significantly to a pathogen’s ability to colonise a niche within the host and cause infection. We have observed that the opportunistic bacterium Serratia marcescens, an important nosocomial pathogen, is highly adept at inhibiting rivals. Additionally, comparative genomics of a small number of clinical isolates has indicated the possession of multiple strain-specific inter-bacterial competition mechanisms in S. marcescens. We will investigate the spread of interbacterial competition mechanisms, including protein secretion systems, within a collection of clinical isolates of S. marcescens, using whole genome sequencing (WGS) and comparative genomics. Novel or previously unidentified competition mechanisms in S. marcescens, identified from comparative genomics will be tested for their ability to confer bacterial killing or inhibition in vitro and subsequently in vivo in a mouse model of pneumonia. Through this work, we aim to elucidate the extent and contribution of inter-bacterial competition to S. marcescens pathogenic success, and by extension, to that of opportunistic Gram-negative bacteria more generally. This may pave the way for future work aiming to combat hospital-acquired infections.