Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking.
Date on Master's Thesis/Doctoral Dissertation
Microbiology and Immunology
Microbiology and Immunology, PhD
Committee Co-Chair (if applicable)
Macrophage; Yersinia pestis; Rab GTPase; Phagosome; RNAi; Pathogens
Y. pestis is a facultative intracellular pathogen and the causative agent of plague. This bacterium, while most noted or the Black Death during the European 14th century, is not a historic pathogen but a re-emerging pandemic with both domestic and global impact. Y. pestis is capable of colonizing the macrophage, and actively subverts phagolysosome maturation to establish a replicative niche known as the Yersinia containing vacuole (YCV). The exploited host factors required to support the YCV are unknown. Here we identified a comprehensive list of host factors required for Y. pestis survival through a genome-wide RNAi high-throughput screen. We further identify that avoidance of the phagolysosome requires early recruitment of Rab1b and Rab4a on the YCV. Finally, we show that during intracellular infection Y. pestis sequesters Rab11b to the YCV to stall host cell recycling and support bacterial replication after 8 hours post-infection. These data identify the first host factors required for Y. pestis survival within the macrophage, avoidance of phagolysosome maturation, and a novel role for exploiting the host recycling pathway for bacterial replication.
Connor, Michael Graylin, "Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking." (2016). Electronic Theses and Dissertations. Paper 2378.
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