TitleThe Voltage-Dependent Anion Channels (VDAC) of Mycobacterium avium phagosome are associated with bacterial survival and lipid export in macrophages.
Publication TypeJournal Article
Year of Publication2017
AuthorsDanelishvili, L, Chinison, JJJ, Pham, T, Gupta, R, Bermudez, LE
JournalSci Rep
Date Published2017 08 01
KeywordsHumans, Lipid Metabolism, Macrophages, Microbial Viability, Mycobacterium avium, Phagosomes, Protein Binding, THP-1 Cells, Voltage-Dependent Anion Channel 1

Mycobacterium avium subsp. hominissuis is associated with infection of immunocompromised individuals as well as patients with chronic lung disease. M. avium infects macrophages and actively interfere with the host killing machinery such as apoptosis and autophagy. Bacteria alter the normal endosomal trafficking, prevent the maturation of phagosomes and modify many signaling pathways inside of the macrophage by secreting effector molecules into the cytoplasm. To investigate whether M. avium needs to attach to the internal surface of the vacuole membrane before releasing efferent molecules, vacuole membrane proteins were purified and binding to the surface molecules present in intracellular bacteria was evaluated. The voltage-dependent anion channels (VDAC) were identified as components of M. avium vacuoles in macrophages. M. avium mmpL4 proteins were found to bind to VDAC-1 protein. The inactivation of VDAC-1 function either by pharmacological means or siRNA lead to significant decrease of M. avium survival. Although, we could not establish a role of VDAC channels in the transport of known secreted M. avium proteins, we demonstrated that the porin channels are associated with the export of bacterial cell wall lipids outside of vacuole. Suppression of the host phagosomal transport systems and the pathogen transporter may serve as therapeutic targets for infectious diseases.

Alternate JournalSci Rep
PubMed ID28765557
PubMed Central IDPMC5539096
Grant ListP30 EY010572 / EY / NEI NIH HHS / United States
S10 RR025571 / RR / NCRR NIH HHS / United States
R01 AI043199 / AI / NIAID NIH HHS / United States
S10 OD012246 / OD / NIH HHS / United States
P30 CA069533 / CA / NCI NIH HHS / United States