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Borrelia gene products critical for natural infection cycle

Award Number: R01AI080615
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: 07/01/2009
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Borrelia gene products critical for natural infection cycle - PROJECT SUMMARY/ABSTRACT Lyme borreliosis, also known as Lyme disease, remains a prevalent tick-borne infection in many parts of the world. In the United States alone, there are over 300,000 new cases occurring each year. The infection is caused by Borrelia burgdorferi sensu lato, which is a group of atypical extracellular bacterial pathogens that survive in nature through a complex enzootic infection cycle, involving ticks belonging to the Ixodes scapularis complex and an array of vertebrate hosts, most commonly wild rodents. Despite serious efforts to control the infection over the past several decades, the infection persists, largely due to the absence of effective control measures against tick infestation, lack of human vaccines, difficulties in diagnosis of early infection, and clinical complications associated with treatment using currently-available antimicrobials. Specifically, several months after standard-care antibiotic therapy, a subset of patients can experience a series of persistent or relapsing symptoms, known as chronic Lyme disease or post-treatment Lyme disease syndrome, for which further treatment options remain unavailable. Therefore, the development of vaccines and new drugs is highly warranted to combat Lyme disease. This project pursues a long-term goal to understand the biological significance of a critical set of microbial virulence determinants and gain knowledge necessary for the development of new therapeutic strategies to intervene with Lyme borreliosis. The emphasis is on protein- protein interactions essential for pathogen infection and persistence in the host, and the goal is to provide comprehensive structural and functional information that defines the biological significance of three spirochete proteins annotated as BB0323, BB0238, and BB0104 (BbHtrA), each of which either independently or as a complex are essential for infection. The previous project cycle demonstrated that the targeted deletion or alteration of either protein partners or short binding epitopes impact protein stability and render the pathogen non-infectious in a mammalian host. The overall objective of the current proposal is to further focus on BB0323 and associated proteins in order to: 1) define the specific events of protein maturation, 2) determine protein-protein interactions, and 3) contribute to the determination of their structures to better understand their roles in dictating spirochete infection in mammals and transmission from ticks. These studies will enlighten our fundamental knowledge of the atypical biology of spirochetes and will facilitate the design of non-traditional anti-infective strategies to combat Lyme borreliosis, including the development of vaccines, small molecule drugs, and biologics.


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 = $474,580 )
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	12	7/2/2024	NON-COMPETING CONTINUATION	$474,580
														Subtotal = $474,580

Issue Date FY: 2023 ( Subtotal = $486,653 )
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	11	7/28/2023	NON-COMPETING CONTINUATION	$486,653
														Subtotal = $486,653

Issue Date FY: 2022 ( Subtotal = $721,843 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	10	8/15/2022	SUPPLEMENT FOR EXPANSION	$223,177
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	10	7/5/2022	NON-COMPETING CONTINUATION	$498,666
														Subtotal = $721,843

Issue Date FY: 2021 ( Subtotal = $498,543 )
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	9	8/20/2021	COMPETING CONTINUATION	$498,543
														Subtotal = $498,543

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	8	5/16/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $380,000 )
2017	2017	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	8	7/20/2017	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2016 ( Subtotal = $380,000 )
2016	2016	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	7	7/9/2016	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2015 ( Subtotal = $380,000 )
2015	2015	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	6	6/26/2015	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2014 ( Subtotal = $380,000 )
2014	2014	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	5	8/26/2014	COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2012	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	4	7/2/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $367,538 )
2012	2012	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	4	6/28/2012	NON-COMPETING CONTINUATION	$367,538
														Subtotal = $367,538

Issue Date FY: 2011 ( Subtotal = $367,538 )
2011	2011	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	3	6/14/2011	NON-COMPETING CONTINUATION	$367,538
														Subtotal = $367,538

Issue Date FY: 2010 ( Subtotal = $371,250 )
2010	2010	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	2	6/14/2010	NON-COMPETING CONTINUATION	$371,250
														Subtotal = $371,250

Issue Date FY: 2009 ( Subtotal = $375,000 )
2009	2009	UNIVERSITY OF MARYLAND	4101 CHESAPEAKE BLDG	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	1	6/25/2009	NEW	$375,000
														Subtotal = $375,000

Grand Total All Awards = $5,182,945

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Borrelia gene products critical for natural infection cycle

Award Number: R01AI080615

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: 07/01/2009

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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