Using Molecular Techniques to Define the Role of Glycopeptidolipids in Mycobacterium avium Pathogenesis

Mycobacterium avium is an environmental bacteria that can cause disease in people with pre-existing lung conditions or who are immunocompromised. Mycobacteria are well known for their complex cell envelope structure and many of the components of the envelope play a significant role in bacterial pathogenesis. The outer leaflet of M. avium bacteria and other non-tuberculosis mycobacteria (NTMs) contain unique, surface-exposed, antigenic molecules known as glycopeptidolipids (GPLs) that are able to interact with host immune receptors including the mannose receptor (MR). These molecules have also been implicated in immune response modulation, transcriptional modification, virulence, sliding motility, and biofilm formation. As GPLs are likely one of the first molecules that the host immune cells interact with, determining the importance of GPLs in the context of an infection could be an important step for understanding how the host initially responds to M. avium. Our work aims to develop an effective transformation method for creating GPL mutant strains in M. avium and determine how GPL interaction with a specific pattern recognition receptor, the MR, can alter the transcriptional profile of primary murine bone-marrow macrophages.