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Antigenic variation in microbial transmission

Award Number: R37AI044005
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: 12/01/1998
PERIOD OF PERFORMANCE END DATE: 11/30/2019

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Antigenic variation in microbial transmission - The goal of the proposed research is determine how competition at the level of host population immunity and transmission fitness drives genetic diversification of microbial pathogens-changes that underlie shifts in disease pattern and are fundamental to the understanding of how new pathogens emerge. Specifically, we are focused on microbial pathogens that employ gene conversion as a mechanism to generate antigenic variants, evade clearance by the immune system, and persist within mammalian host reservoirs-pathogens that can be broadly diverse in taxon (e.g. the bacterium Borrelia versus the protozoa Trypanosoma) but united by these common persistence and variant evolution mechanisms. These pathogens generate within- host antigenic variants using genomic complements of variant donor alleles. There is strong selective pressure for sufficient diversity among the variant alleles in the genome to evade clearance and persist, as within host persistence dramatically increases the likelihood of successful ongoing transmission. This pressure alone would lead to strain homogeneity as defined by the allelic repertoire within a pathogen species rather than the emergence and heterogeneity. In our work, we identified strain superinfection as an opposing selective pressure that drives allelic diversification among strains of a pathogen, strain emergence, and heterogeneity. Penetration of a new strain into a region with a high prevalence of infection and consequent broad immunity against the variants encoded by an existing endemic strain requires that the new strain encode variants that will be immunologically novel and allow establishment of infection. This pressure is hypothesized to favor continual genetic probing for selective advantage and to result in the genetic change that underlies shifts in transmission and disease patterns. Understanding how this occurs in bacteria and protozoa, complex pathogens that cannot rely on mutation and the large progeny burst size as do viruses, and the consequences for transmission within endemic zones is the goal. Using Anaplasma marginale as a model in which we can study pathogen infectivity and transmission in a natural mammalian host, we determine how the two contrasting selective pressures mold strain structure and test the kinetics of new strain emergence in the host population. Importantly, we link the effect of strain emergence, defined by expression of a novel variant-encoding allele, on its transmission fitness and persistence and expansion in the host population. This knowledge of the kinetics of pathogen emergence is critically important to understand how new genomically complex pathogens fail or succeed in changing disease patterns.


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: 2020 ( Subtotal = -$760 )
2020	2018	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	20	3/18/2020	NON-COMPETING CONTINUATION	-$760
														Subtotal = -$760

Issue Date FY: 2018 ( Subtotal = $339,750 )
2018	2018	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	20	11/9/2017	NON-COMPETING CONTINUATION	$339,750
														Subtotal = $339,750

Issue Date FY: 2017 ( Subtotal = $339,750 )
2017	2017	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	19	11/9/2016	NON-COMPETING CONTINUATION	$339,750
														Subtotal = $339,750

Issue Date FY: 2016 ( Subtotal = $339,750 )
2016	2016	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	18	12/2/2015	NON-COMPETING CONTINUATION	$339,750
														Subtotal = $339,750

Issue Date FY: 2015 ( Subtotal = $339,750 )
2015	2015	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	17	10/31/2014	NON-COMPETING CONTINUATION	$339,750
														Subtotal = $339,750

Issue Date FY: 2014 ( Subtotal = $339,750 )
2014	2014	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	002	16	6/9/2014	EXTENSION WITH OR WITHOUT FUNDS	$33,975
2014	2014	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	16	11/21/2013	EXTENSION WITH OR WITHOUT FUNDS	$305,775
2014	2013	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	001	15	11/21/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $339,750

Issue Date FY: 2013 ( Subtotal = $309,902 )
2013	2013	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	003	15	11/21/2013	NON-COMPETING CONTINUATION	$0
2013	2013	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	15	11/20/2012	NON-COMPETING CONTINUATION	$296,714
2013	2013	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	002	15	6/13/2013	NON-COMPETING CONTINUATION	$13,188
2013	2013	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	001	15	1/11/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $309,902

Issue Date FY: 2012 ( Subtotal = $329,682 )
2012	2012	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	001	14	5/29/2012	NON-COMPETING CONTINUATION	$32,968
2012	2012	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	14	11/25/2011	NON-COMPETING CONTINUATION	$296,714
														Subtotal = $329,682

Issue Date FY: 2011 ( Subtotal = $329,682 )
2011	2011	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	13	11/15/2010	NON-COMPETING CONTINUATION	$299,710
2011	2011	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	001	13	6/2/2011	NON-COMPETING CONTINUATION	$29,972
														Subtotal = $329,682

Issue Date FY: 2010 ( Subtotal = $333,011 )
2010	2010	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	002	12	5/28/2010	NON-COMPETING CONTINUATION	$30,273
2010	2010	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	001	12	12/1/2009	NON-COMPETING CONTINUATION	$302,738
2010	2009	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Allergy and Infectious Diseases Research	000	11	12/1/2009	COMPETING CONTINUATION	$0
														Subtotal = $333,011

Grand Total All Awards = $3,000,267

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Antigenic variation in microbial transmission

Award Number: R37AI044005

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: 12/01/1998

PERIOD OF PERFORMANCE END DATE: 11/30/2019

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