Understanding bacterial host adaptation to combat infectious disease

The emergence of new pathogens via host jumps from other host species is a major threat to public health and food security. In addition, antimicrobial resistance has reached crisis proportions and novel approaches for controlling bacterial infections are urgently required. Staphylococcus aureus is a major pathogen that has undergone numerous host-switching events during its evolutionary history leading to the emergence of new pandemic human and livestock clones. In the current proposal, we will employ S. aureus as a model to investigate the critical evolutionary events, and key host-pathogen interactions which underpinned the successful adaptation of S. aureus to different host-species. Building on a recent collaboration of two of the investigators that revealed the critical adaptive mutations required for S. aureus infectivity of rabbits, we will use a combination of high-resolution phylogenetic analyses, molecular microbiological and immunological techniques, allied with integrated chemical biophysics platforms to reconstruct the evolutionary trajectory and molecular basis of S. aureus host-adaptation. Identification of the key bacterial and host determinants involved will allow investigation into their potential as novel targets for prevention or treatment of human and livestock infections. Importantly, the approaches employed and the insights provided will be widely applicable to other major pathogens.