Project No. 2138

Primary Supervisor

Dr Christopher Mulligan – University of Kent

Co-Supervisor(s)

Prof Jonathan Essex – University of Southampton

Dr Mark Paget – University of Sussex

Summary

The alarming global progression of antimicrobial resistance threatens to propel humankind into a post-antibiotic era where illnesses and injuries that are currently trivial to treat become life-threatening conditions.

Unchecked, the global death toll could exceed 10 million deaths per year by 2050, even exceeding cancer-related deaths. Developing new antibiotics is essential, but this is slow and expensive, and the chances of bacteria developing resistance is high. A promising, complementary approach to help combat resistance is to reduce resistance itself. By identifying pathways that, when disrupted, sensitise resistant bacteria to antibiotics, we could breathe new life into drugs rendered obsolete, and boost the potency of newly developed drugs. The DedA family are integral membrane proteins that contribute to antibiotic resistance in clinically relevant pathogenic bacteria; including being essential for resistance to colistin, which is a drug of last resort used in the treatment of multidrug-resistant bacterial infections. Thus, DedA proteins present an attractive target in the pursuit of antibiotic potentiators. However, the DedA family is very mysterious; while hypothesised to be transport proteins, their structure, function, and physiological role are unknown. In this project, we will use a multipronged approach to illuminate the physiological role of the DedA family. We will assess the effects of gene knockout mutants in a variety of bacterial species; investigate DedA function