Growth in biofilms prepares Mycobacterium avium susp. hominissuis for the transition to the macrophage microenvironment

William McManusKatie MulveyElizabeth BrooksSheri SandersJeff Schorey^*

• University of Notre Dame, Notre Dame, United States

Mycobacterium avium subs. hominissuis (MAH) is an opportunistic pathogen, causing pulmonary infections in individuals who are immunocompromised or whose respiratory systems are damaged due to injuries or diseases such as cystic fibrosis, bronchiectasis, or chronic obstructive pulmonary disease. MAH is an environmental microbe commonly found in numerous natural and engineered habitats, including marginal niches where few species are able to survive. MAH is able to persist in these habitats through biofilm formation, a process in which the hydrophobic mycobacterial cells preferentially adhere to a surface or to particles in suspension. The process of biofilm formation as well as the movement of MAH from its environmental niche into a host entails a large shift in conditions and stressors. To mediate these transitions, it is necessary that MAH responds by modulating its gene expression. We used next generation sequencing to define changes in MAH gene expression that occur during biofilm formation and during transition to survival inside host macrophages. We identified genes that are differentially expressed in two different MAH biofilm models relative to planktonic MAH. We also identified genes that show differential expression in MAH isolated from both infected macrophages and in biofilms when compared to planktonic MAH. For some of these genes, we did not observe notable changes in expression in biofilm-grown MAH pre-and post-infection, suggesting that genes expressed during residence in a biofilm may condition MAH to survive in a macrophage. Overall, these results identify a number of genes that may be important for biofilm formation and survival within macrophages and which will provide new foci for drug development that targets biofilm formation and MAH virulence.