Identification of factors that modulate Yop translocation during animal and tissue culture infection of Yersinia pseudotuberculosis.
Keith, Julia.
2015
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Abstract: The gram-negative pathogen, Yersinia pseudotuberculosis evades the host immune system by injecting effector proteins (Yops) into host cells through its type III secretion system. These effector proteins disarm host defenses and allow the bacteria to establish infection. Both host and bacterial factors modulate Yop translocation. Bacterial growth during animal infection is controlled by n... read moreeutrophils, iMo, and iDC. These cells are selectively targeted for Yop translocation and are essential for controlling Yersinia infection. Translocation of Yops into host cells is largely abolished in the absence of neutrophils, iMo and iDC. Here we show that in the absence of neutrophils alone, Yop translocation levels are higher than expected. By microscopic analysis of infected spleens, we found that small microcolonies are formed in the absence of neutrophils, while very large microcolonies are formed in the absence of iMo and iDCs. We propose that since smaller microcolonies allow for more contact of the bacteria with host cells, the smaller colonies formed in the absence of neutrophils result in higher numbers of Yop-intoxicated host cells. We also report that the adhesin YadA is required for the formation of large microcolonies. Calcium flux may be required to prime host cells to be translocated with Yops. Neutrophils undergo calcium flux when responding to infection, and when exposed to Yersinia byproducts. In neutropenic and monocytic cell lines, chemically inducing a calcium flux increased Yop translocation. In contrast, blocking calcium flux with chemical inhibitors decreased Yop translocation into these cell lines. Combined, these results suggest that calcium flux enhances translocation of Yops, and that signals that trigger recognition of pathogens may prime cells for Yop delivery. Additionally, we further characterized dynamics of translocation and Rho-GAP activity of YopE, an effector protein that regulates effector translocation into host cells.
Thesis (Ph.D.)--Tufts University, 2015.
Submitted to the Dept. of Molecular Microbiology.
Advisor: Joan Mecsas.
Committee: Linden Hu, Abraham Sonenshein, and Ralph Isberg.
Keywords: Microbiology, and Immunology.read less - ID:
- ws859t58x
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