Identification of Mycobacterium avium genes expressed during in vivo infection and the role of the oligopeptide transporter OppA in virulence

•Mycobacterium avium secretes MAV_2941 protein in the macrophage cytosol.•The MAV_2941 is transported by the OppA oligopeptide transporter.•Inactivation of both, OppA and MAV_2941 attenuated the bacterium in macrophages and in vivo.

Mycobacterium avium causes disseminated disease in patients with AIDS and other immunosuppressive conditions and pulmonary infections in individuals with chronic lung diseases. Much still need to be learn about the mechanisms of M. avium pathogenesis. Using a mouse model of disseminated M. avium disease, we applied an in vivo expression technology system and identified M. avium genes up-regulated in different organs of mice during early stage of infection. The M. avium oppA gene, involved in an active transport of oligopeptides across the cell membrane, was found highly expressed in lung, liver and spleen of mice. Mutation in the transport domain of the oppA gene resulted in bacterial attenuation in both macrophages and in mice. Using protein-protein interaction assay, it was determined that two hypothetical small proteins, MAV_2941 (73aa) and MAV_4320 (45aa), interact with OppA. MAV_2941 was shown to be secreted by the bacterium into the macrophage cytoplasm. Mutations in MAV_2941 was associated with significant impairment of growth in macrophages. Understanding the mechanisms involved in the functions of MAV_2941 and MAV_4320 is warranted.