Honors College Thesis
 

Interaction of the human Voltage-Dependent Anion Channel 1 protein (VDAC-1) with Mycobacterium avium and its role in bacterial survival within phagocytic cells

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https://ir.library.oregonstate.edu/concern/honors_college_theses/1c18dh757

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  • M. avium is an opportunistic pathogen that primarily infects macrophages. In order to survive within the macrophage, M. avium secretes proteins into the host cell cytoplasm to inhibit specific functions such as phagosome acidification, altering pathways as well as initiating apoptosis. However, little is known about how those secreted proteins are exported into the host cell. The goal of this study was to identify and characterize the mechanism that allows M. avium to transport proteins into the macrophage cytosol. Magnetic labeling technology was used to isolate phagosomes containing M. avium. Through mass spectroscopy, we were able to identify a potential channel, voltage dependent anion channel 1 protein (VDAC-1), on the membrane of the phagosome and also bound to M. avium surface. Cyclosporine A (CsA), an inhibitor of Ca²⁺ dependent pores, was used to inhibit VDAC-1. Growth of bacteria in CsA–treated macrophages at 1d, 2d and 3d was significantly lower compared to bacteria in untreated macrophages. Similar results were observed using small interfering RNA (siRNA) to knockdown the expression of VDAC-1 in macrophages. The observed bacterial growth at 1d was significantly decreased compared to bacteria in untreated and in siRNA control groups. Differences between siRNA treated group and control groups on 2d and 3d continued to be significant. The observations above suggested that functional VDAC-1 has an important role for the survival of intracellular M. avium.
  • Key Words: M. avium, phagosome, voltage dependent anion channel 1 protein, cyclosporine A, siRNA
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