Characterising the mechanisms of cell-cell interactions sheds light on new avenues to combat infection

The spread of antimicrobial resistance (AMR) is accelerating at an alarming rate, threatening the treatment of infectious disease and other medical interventions, due to an increased risk of infection that we no longer possess effective treatments for. Long reliance on evolutionarily-static, conventional antibiotics to treat bacterial infection has fuelled resistance selection and the need for the constant discovery of new classes of antibiotics to replace those whose effectiveness is being lost. This MRes thesis is the culmination of two rotation projects, based at the University of Birmingham and the University of Nottingham; the first investigated the underlying mechanisms behind the immune perturbation induced by vancomycin on host macrophages, ultimately resulting in an impaired control of infection, predisposing to systemic fungal infection. Future elucidation of the mechanisms underlying this predisposition to fungal infection will aid antibiotic stewardship and clinical practise regarding the implication of current and new antimicrobial therapies. The second study investigated the role of three hypothetical proteins, predicted to be contained within a predatory vesicle whose composition and function is being actively investigated within the lab, within the predatory lifecycle of the predatory bacterium Bdellovibrio bacteriovorus. By providing a better understanding of the complex predatory process, this study aids the potential utilisation of B. bacteriovorus, or components of its predatory lifecycle, as novel antimicrobial therapeutics in the future. Future work will further confirm the roles of these proteins within the wider context of predation and infection. To develop successful antimicrobial therapies in the future and combat the AMR crisis, the host immune system and novel or chemical antimicrobial therapies must work hand in hand. This will only be possible through the greater understanding of the interactions that occur between current and novel antimicrobial therapies and the host immune system.