Publication Date

2014-11-17

Availability

Open access

Embargo Period

2014-11-17

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Microbiology and Immunology (Medicine)

Date of Defense

2014-11-05

First Committee Member

Kurt Schesser

Second Committee Member

Gregory Plano

Third Committee Member

Wasif Khan

Fourth Committee Member

Robert Levy

Fifth Committee Member

Antonio Barrientos

Sixth Committee Member

Ralf Landgraf

Abstract

During an infectious process, bacterial pathogens interact with host innate immune cells. These innate cells (primarily macrophages) play a major role in the antimicrobial defense and bacterial clearance. In this work, we identify the niche which Yersinia pseudotuberculosis creates during macrophage contact. We show that the pYV virulence plasmid is essential for the ability of the bacterium to create an acidified, partially enclosed, and durable niche along the macrophage surface. These compartments are uncoupled from the normal host cell endocytic trafficking pathway and are exposed to the extracellular medium. We present data which shows that the formation of the Yersinia Acidified Compartment (YAC) is independent of type III secretion system mediated translocation of effectors into the host cell. However, the maintenance of the YAC requires a fully functional type III secretion system, especially the effector YopJ which seems to play an important role in YAC maintenance. We provide evidence that the loss of YAC acidity by exogenous neutralizing agents or through deletion of YopJ is detrimental to Yersinia viability during macrophage contact. We also show that when expressed in fission yeast, the GFP-YopJ fusion is able to undergo a stress dependent subcellular redistribution which requires the first 70 amino acids of YopJ. We also show that YopJ is able to impose an endosomal trafficking defect in fission yeast cells. Taken together, our data sheds light on the unique structure which Yersinia creates along the macrophage border, its importance as well as bacterial factors which are involved in its creation.

Keywords

Yersinia, acidified, compartment

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