Project Title: Optimising treatment options for multidrug-resistant Mycobacterium abscessus: Elucidating the molecular basis of aminoglycoside resistance.
Project Summary: Multidrug resistant Mycobacterium abscessus is emerging as a priority, high-risk, chronic infection in structural lung disease in both high- and low-income settings. It permanently damages lung tissue and accelerates lung function decline, leading to high morbidity and mortality. Antibiotic treatments are for a minimum of 12 months, yet only about 50% of patients achieve clinical cure. Pilot data I have generated indicate that treatment is sub-optimal due to poorly understood intrinsic antimicrobial resistance mechanisms. Using molecular and genetic methodologies, I will characterise aminoglycoside-modifying enzymes and examine their roles in treatment failure and then apply this knowledge to inform optimisation of novel combination treatment strategies.