Date on Master's Thesis/Doctoral Dissertation

5-2016

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Microbiology and Immunology

Degree Program

Microbiology and Immunology, PhD

Committee Chair

Lawrenz, Matthew

Committee Co-Chair (if applicable)

Chung, Donghoon

Committee Member

Chung, Donghoon

Committee Member

Abu-kwaik, Yousef

Committee Member

Worley, Micah

Committee Member

Suttles, Jill

Author's Keywords

Macrophage; Yersinia pestis; Rab GTPase; Phagosome; RNAi; Pathogens

Abstract

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.

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