PublisherThe University of Arizona.
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AbstractAutophagy is the intracellular degradative process whereby cellular components are broken down and recycled. This process plays a role in regulation of cellular homeostasis and in intracellular defense against invasive pathogens. Pathogen Neisseria gonorrhoeae (Ngo) causes a sexually transmitted disease and has an intracellular phase in its life cycle. Ngo attaches to human epithelial cells for extensive periods of time, however, few viable intracellular bacteria are recovered until 4 hours post-infection. We observed an increase in viable intracellular CFU count when lysosome formation was inhibited. Since autophagy is a lysosome-dependent mechanism, we seek to determine whether autophagy influences intracellular survival of Ngo. With the use of chemical inhibitors, RNAi, immunoblots and immunofluorescence microscopy, we show that autophagy is induced by Ngo through the Type I membrane protein CD46-cyt1 and its interacting partner GOPC. Although this autophagic response kills off early invaders, Ngo is able to promote its intracellular survival at later stages in infection by inducing shedding of CD46 and remodeling lysosomes. This mechanism allows Ngo to inhibit initiation of autophagy and reduce degradation of cell parts and pathogens in the autophagic complex.
Degree ProgramHonors College