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Ail-mediated serum resistance in Yersinia pestis and its contribution to plague virulence

Award Number: R21AI133570
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: 05/07/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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Ail-mediated serum resistance in Yersinia pestis and its contribution to plague virulence - Summary Ail is a multifunctional surface protein required for virulence in Yersinia pestis, the etiological agent of plague. Ail confers serum-resistance, facilitates Type Three Secretion (T3S) of cytotoxins into host cells and mediates adhesion to host cells via extracellular matrix (ECM) proteins. While Ail is required for Y. pestis virulence in animal models, it remains unclear which activities make major contributions to the establishment of plague. Our previous studies have defined the mechanism for Ail binding to host cells to provide Ail-mediated Yop delivery. While some such Ail mutants are nearly completely defective for Ail-mediated Yop delivery, they still impart strong serum resistance. In this proposal we will determine the mechanism(s) by which Ail confers serum resistance to Y. pestis. This involves investigating Ail interaction with various complement proteins involved in assembly of the membrane attack complex (MAC) including C6-C9 and the complement regulatory proteins Factor H and vitronectin. Using a newly generated serum-sensitive mutant of Ail that maintains Yop delivery activity, we will test the effects of serum-sensitive or adhesion/Yop delivery defective derivatives of Ail on plague pathogenesis in rats (rats are a good model for serum-related aspects of human disease). We hypothesize that loss of Ail- mediated cell binding or serum-resistance will lead to intermediate defects in host colonization, but loss of both activities will result in attenuation similar to a Dail mutant. In all, this proposal focuses on the critical nature of interaction between Ail and the host. Specifically, we will establish the roles of Ail-mediated serum-resistance and adhesion/Yop translocation in plague pathogenesis, a longstanding challenge for the field.


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: 2024 ( Subtotal = -$149 )
2024	2019	UNIVERSITY OF DETROIT MERCY	4001 W MCNICHOLS RD	DETROIT	MI	48221	WAYNE	USA	Allergy and Infectious Diseases Research	000	2	10/17/2023	NON-COMPETING CONTINUATION	-$149
														Subtotal = -$149

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	UNIVERSITY OF DETROIT MERCY	4001 W MCNICHOLS RD	DETROIT	MI	48221	WAYNE	USA	Allergy and Infectious Diseases Research	000	2	7/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF DETROIT MERCY	4001 W MCNICHOLS RD	DETROIT	MI	48221	WAYNE	USA	Allergy and Infectious Diseases Research	000	2	9/29/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $203,387 )
2019	2019	UNIVERSITY OF DETROIT MERCY	4001 W MCNICHOLS RD	DETROIT	MI	48221	WAYNE	USA	Allergy and Infectious Diseases Research	000	2	4/24/2019	NON-COMPETING CONTINUATION	$203,387
														Subtotal = $203,387

Issue Date FY: 2018 ( Subtotal = $161,413 )
2018	2018	UNIVERSITY OF DETROIT MERCY	4001 W MCNICHOLS RD	DETROIT	MI	48221	WAYNE	USA	Allergy and Infectious Diseases Research	000	1	5/7/2018	NEW	$161,413
														Subtotal = $161,413

Grand Total All Awards = $364,651

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Ail-mediated serum resistance in Yersinia pestis and its contribution to plague virulence

Award Number: R21AI133570

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: 05/07/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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