P234 Investigating the role of hypoxia in driving the adaptation of Mycobacterium abscessus infection in cystic fibrosis

Abstract

Chronic infection by opportunistic pathogens is a major contributor to mortality in people with cystic fibrosis (CF). It is well-documented that bacteria adapt over time of colonisation to thrive in the CF lung; however, the mechanisms underlying these adaptations are poorly understood. Mycobacterium abscessus (Mab) is an emerging pathogen in CF as its prevalence has increased sharply in the last 20 years. Mab causes recalcitrant antibiotic resistant, pulmonary infections. Key to its success is its ability to adapt to hypoxic conditions typical of the CF lung niche. The DosR regulon, which controls dormancy and hypoxic response in mycobacteria is activated in hypoxic conditions. Genes within this regulon such as DosS and R, universal stress proteins (USPs), nitroreductases and ATPases display robust up-regulation in hypoxia.