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Elucidating the Biogenesis of the Yersinia pestis Containing Vacuole

Award Number: R21AI119557
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2016
PERIOD OF PERFORMANCE END DATE: 02/28/2019

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Elucidating the Biogenesis of the Yersinia pestis Containing Vacuole - ¿ DESCRIPTION (provided by applicant): Yersinia pestis is a facultative intracellular pathogen that causes the disease known as plague. Growing evidence indicates that intracellular growth in macrophages is important for Y. pestis virulence. Upon phagocytosis, Y. pestis alters the maturation of the phagosome to generate a protective compartment within the cell known as the Yersinia containing vacuole (YCV). Key steps in the generation of the YCV include inhibition of YCV acidification, expansion into a spacious vacuole, and acquisition of the autophagic markers. However, the mechanisms used by the bacterium to subvert the normal phagosome maturation process and generate the YCV have not been defined. Recently we have identified a subset of host Rab GTPases that are required for Y. pestis to survive within macrophages. Because Rab proteins are key mediators of vesicular trafficking, phagosome maturation, and autophagy, we hypothesize that these GTPases are required by Y. pestis to subvert phagosome maturation and generate the YCV, thus protecting the bacterium from macrophage clearance. As Rab proteins mediate many aspects of vesicular trafficking through direct interactions with specific organelles and recruitment of effector proteins, in Aim 1 we will determine if Rab GTPase required for Y. pestis intracellular survival are specifically recruited to the YCV. In Aim 2, we will determine the contribution of individual Rab proteins on the biogenesis of the YCV. These studies will be the first to define the contribution of host Rab GTPases to the formation of the YCV. Ultimately, understanding the YCV biogenesis process will enable us to identify Y. pestis pathogenicity factors that contribute to intracellular survival.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2019 ( Subtotal = -$5,028 )
2019	2017	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Microbiology and Infectious Diseases Research	000	2	7/25/2019	NON-COMPETING CONTINUATION	-$5,028
														Subtotal = -$5,028

Issue Date FY: 2017 ( Subtotal = $188,418 )
2017	2017	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Microbiology and Infectious Diseases Research	000	2	2/21/2017	NON-COMPETING CONTINUATION	$188,418
														Subtotal = $188,418

Issue Date FY: 2016 ( Subtotal = $224,415 )
2016	2016	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Microbiology and Infectious Diseases Research	000	1	2/29/2016	NEW	$224,415
														Subtotal = $224,415

Grand Total All Awards = $407,805

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Elucidating the Biogenesis of the Yersinia pestis Containing Vacuole

Award Number: R21AI119557

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2016

PERIOD OF PERFORMANCE END DATE: 02/28/2019

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