Understanding the pathobiology of Mycobacterium abscessus infection

Mycobacterium abscessus is an intrinsically multidrug-resistant species of nontuberculous mycobacteria (NTM) that has recently emerged as a major threat to individuals with cystic fibrosis (CF) and other chronic lung conditions, including non-CF bronchiectasis. In CF, M. abscessus drives accelerated inflammatory lung damage, is frequently impossible to treat, and usually prevents safe lung transplantation. Infection rates are increasing globally, which we have shown are driven (at least in part) by indirect person-to-person transmission of M. abscessus, probably through the generation of long-lived infectious aerosols and via fomite spread.

We currently do not understand how M. abscessus interacts with macrophages and epithelial cells to cause lung infection or the reasons why some individuals are susceptible to infection. There is therefore a critical unmet need to better understand the pathophysiology of this organism and the mechanisms of human susceptibility to M. abscessus to thereby identify therapeutic targets and discover strategies to mitigate infection risk.

Our aims are therefore to:

- explain how horizontal gene transfer and within-host evolution have shaped M. abscessus virulence.

- define key pathways involved in pathogenesis through transcriptional analysis of bacteria and host

- understand the mechanisms causing susceptibility to M. abscessus infection in CF and non-CF individuals.