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Delineating adaptive mechanisms of tick-borne relapsing fever spirochetes within the argasid vector.

Award Number: R21AI174279
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: 11/21/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2026

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Delineating adaptive mechanisms of tick-borne relapsing fever spirochetes within the argasid vector. - Project Summary Microbial adaptation within different natural environments is a poorly understood area of emerging infectious disease research and is relevant toward improving public health. For example, tick-borne relapsing fever (RF) spirochetes are a significant yet understudied public health problem. The pathogens colonize insect and tick vectors including Ornithodoros species. These ticks are long lived (10 – 20 years), possess multiple nymphal stages, and maintain RF spirochetes transstadially and transovarially. Within the Ornithodoros species, RF spirochetes persistently colonize the immunological and physiological disparate environments of the midgut and salivary glands. An important aspect of vector competence for RF spirochetes is vector specificity. Here, a given RF spirochete species has evolved to colonize a specific species of Ornithodoros tick. For example, nonnative species (i.e. Borrelia hermsii) can infect Ornithodoros turicata, are detected post-molt in the midgut, are initially detected in the salivary glands within 7 to 10 days post-acquisition, but cannot persistently colonize the salivary gland acini post molt. This contrasts the native species (Borrelia turicatae) that persistently colonizes the salivary glands for over five years. These findings and the vague understanding of argasid immunity indicates the need of functional genomics approaches to delineate the mechanisms of vector colonization by RF spirochetes. Recently, four putative antimicrobial peptides in the defensin family were identified. Designated OtdA-OtdD, they have structural features common of defensins. Moreover, they are differentially expressed during the life cycle of uninfected O. turicata, and preliminary data show that otdA and otdC remain up-regulated in infected tick midguts. This further indicates a role of these peptides in immunity. Consequently, in this application a comprehensive (Aim 1) and focused (Aim 2) approach will be implemented to understand argasid immunity. The overall hypothesis is that B. turicatae has uniquely adapted to O. turicata immunity and are resistant to defensin mediated killing. This hypothesis will be tested with two aims. The first aim will exploit the inability of B. hermsii to persistently colonize the salivary glands of O. turicata. The hypothesis is that transcriptional responses of immune related genes are consistent in O. turicata regardless of if the tick is infected with native (B. turicatae) versus nonnative (B. hermsii) spirochetes. This comparative transcriptional analysis will indicate whether B. turicatae has uniquely adapted to the natural immunological responses of the tick and/or if the species modulates host gene expression to generate an environment suitable for colonization. The second aim will evaluate the role of OtdA-OtdD in immunity. The hypothesis is that B. turicatae resists OtdA–OtdD killing while these small proteins are borreliacidal to other species of RF spirochetes. The completion of this aim will determine whether O. turicata OtdA–OtdD are novel tick antimicrobial peptides that are borreliacidal against nonnative species of RF spirochete. Understanding the molecular events occurring in the tick will guide novel control strategies.


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: 2026 ( Subtotal = $0 )
2026	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	2	10/31/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $200,625 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	2	11/7/2024	NON-COMPETING CONTINUATION	$200,625
														Subtotal = $200,625

Issue Date FY: 2024 ( Subtotal = $240,750 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	1	11/21/2023	NEW	$216,675
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	001	1	6/7/2024	NEW	$24,075
														Subtotal = $240,750

Grand Total All Awards = $441,375

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Delineating adaptive mechanisms of tick-borne relapsing fever spirochetes within the argasid vector.

Award Number: R21AI174279

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: 11/21/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2026

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