Mycobacteroides abscessus (Mab; also known as Mycobacterium abscessus) is an emerging opportunistic pathogen. Patients with structural lung conditions such as bronchiectasis, cystic fibrosis, and chronic obstructive pulmonary disease are at high risk of developing pulmonary Mab disease. This disease is often chronic as the current treatment regimens are sub-efficacious. Here, we characterize the phenotype of a Mab strain lacking the MAB_3167c locus, which encodes a protein hereafter referred to as Glby. We demonstrate that the loss of Glby impairs normal planktonic growth in liquid broth, results in longer average cell length, and a melding of surfaces between cells. Glby also exhibits a mild β-lactamase activity. We also present evidence that amino acid substitutions that potentially alter Glby function are not favored. Lastly, we demonstrate that, in a mouse model of pulmonary Mab infection, the mutant lacking Glby was unable to proliferate, gradually cleared, and was undetectable after 3 weeks. These data suggest that an agent that inhibits Glby in vivo may be an efficacious treatment against Mab disease. IMPORTANCE Mycobacteroides abscessus can cause chronic pulmonary infections requiring administration of multiple antibiotics, still resulting in a low cure rate. The incidence of M. abscessus disease is increasing in the United States and the developed regions of the world. We show for the first time that a protein, Glby, affects growth of this bacterium. Using a mouse model of lung M. abscessus disease, we demonstrate that Glby is required for this bacterium to cause disease.
Keywords: Glby; MAB_3167c; Mycobacterium abscessus; Mycobacteroides abscessus; β-lactamase.