Monday, January 19, 2026 1/19/2026

Virulence regulation by BadR in the Lyme disease spirochete

Award Number: R01AI152983
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: 03/24/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Virulence regulation by BadR in the Lyme disease spirochete - ABSTRACT Borrelia burgdorferi (Bb), the etiological agent of Lyme disease, maintains itself in nature via a complex life cycle involving an arthropod (tick) vector and small mammals. During its cycle between ticks and mammals, Bb undergoes dramatic adaptive changes in order to interact with and adapt to these two disparate niches. Previously, we found that BadR, a homologue of ROK repressors, binds to the rpoS promoter region and represses the expression of rpoS. Moreover, our preliminary findings have suggested that BadR has much broader biological relevance to the life cycle of Bb other than repressing rpoS expression. First, BadR is required for Bb's optimal growth. Second, BadR plays a vital role in the establishment of mammalian infection. Contrary to the wild-type strain, a badR deletion mutant is incapable of infecting mice, suggesting that BadR governs expression of key effector proteins associated with Bb's survival in the host. Phenotypic defects of the badR mutant in mice infection are NOT related to the well documented RpoN-RpoS regulatory pathway, because all of BosR, Rrp2, RpoN, and RpoS are still produced in the badR mutant. In fact, our preliminary global transcriptomic analyses using RNA-seq have identified numerous BosR/RpoS-independent genes regulated by BadR. In addition, we found that badR is expressed throughout Bb's tick-mammal infectious cycle. These combined data give rise to our hypothesis that BadR is a master regulator governing Bb's host adaption and virulence expression. This hypothesis will be addressed in two Specific Aims. In Aim 1 of this proposal, we will employ global transcriptome/proteome profiling to define the entire BadR regulon under various in vitro and in vivo conditions. In Aim 2, we will select BadR-regulated genes based on our global transcriptome/proteome analyses and characterize their contributions to Bb's infectious cycle. These combined studies will (i) refine our knowledge on BadR-mediated gene regulation; (ii) provide a transformative understanding of the in vivo importance of the regulon; and (iii) identify novel virulence determinants. Resultant findings could lead to the development of new strategies to prevent and/or treat Lyme disease.


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	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	000	5	1/6/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $373,750 )
2025	2025	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	000	5	2/13/2025	NON-COMPETING CONTINUATION	$373,750
														Subtotal = $373,750

Issue Date FY: 2024 ( Subtotal = $373,750 )
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	001	4	5/24/2024	NON-COMPETING CONTINUATION	$37,375
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	000	4	1/29/2024	NON-COMPETING CONTINUATION	$336,375
														Subtotal = $373,750

Issue Date FY: 2023 ( Subtotal = $373,750 )
2023	2023	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	000	3	2/3/2023	NON-COMPETING CONTINUATION	$373,750
														Subtotal = $373,750

Issue Date FY: 2022 ( Subtotal = $373,750 )
2022	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	000	2	2/14/2022	NON-COMPETING CONTINUATION	$373,750
														Subtotal = $373,750

Issue Date FY: 2021 ( Subtotal = $373,750 )
2021	2021	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Allergy and Infectious Diseases Research	000	1	3/23/2021	NEW	$373,750
														Subtotal = $373,750

Grand Total All Awards = $1,868,750

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Virulence regulation by BadR in the Lyme disease spirochete

Award Number: R01AI152983

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: 03/24/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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