Monday, June 30, 2025 6/30/2025

Determination of the genetic basis for B. burgdorferi mammalian infectivity

Award Number: R01AI099094
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: 06/01/2013
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Determination of the genetic basis for B. burgdorferi mammalian infectivity - PROJECT SUMMARY Lyme disease is the leading tick-borne bacterial disease in the world resulting an estimated 300,000 cases per year in the US alone. Lyme disease is caused by tick-bite transmission of the pathogenic spirochete Borrelia burgdorferi (Bb). An increased understanding of the molecular mechanisms that Bb uses to survive throughout its infectious cycle is critical for the development of innovative diagnostic and therapeutic protocols to reduce the incidence of Lyme disease. Bb harbors a reduced genome lacking many canonical metabolic, virulence and host defense evasion functions and a large number of the genes in the Bb genome encode hypothetical proteins of unknown function uniquely conserved among Borrelia species, together suggesting that Bb has evolved unique mechanisms to survive in the host that remain largely unknown. In the previous funding cycle, we addressed one of the key challenges in the field of Bb molecular pathogenesis, definition of the transcriptional activity of Bb during mammalian infection. Our novel synergistic approach combined development and application of an in vivo expression technology (IVET)-method for Bb, genome-wide identification of the 5' end transcriptome of Bb during growth in culture and infectivity analysis of targeted Bb mutants. This work contributed significant insight into the Bb transcriptome in vitro and during infection and resulted in our discovery of a large number of novel infection-expressed genes likely to contribute to Bb pathogenesis. These findings catalyze our current efforts to address a critical unresolved gap in knowledge of the biology of this pathogen, which is elucidation of the molecular mechanisms that allow Bb to overcome barriers to infection in order disseminate to distal tissues, leading to persistent infection and therefore, the incapacitating symptoms of Lyme disease. The goal of this proposal is to elucidate the molecular mechanisms that Bb uses to overcome host barriers to infection in order to disseminate. To achieve this goal we have focused our studies on functional analysis of three novel genes, bb0318, bbk13 and bb0562, which our data indicate play critical roles in Bb infectivity and dissemination due to their distinct contributions to Bb's ability to evade the early immune responses of the host. We will elucidate the molecular mechanisms of bb0318-dependent resistance to oxidative stress and immune-cell killing (Aim 1) and bbk13-dependent evasion of host complement (Aim 2) as well as define the contribution of bb0562 to Bb infection (Aim 3). We propose a multidisciplinary approach for mechanistic analysis of each of these novel genes, using cutting edge technologies in biochemistry, cell biology, microscopy and innate immunity as well as in vivo live imaging, a diversity of mouse models and an experimental tick-mouse infectious cycle. The insight gained from our work will significantly impact the understanding of the mechanisms of Bb dissemination, which in turn will provide a foundation for novel approaches for Lyme disease interventions.


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 = $0 )
2024	2022	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	9	3/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $407,035 )
2022	2022	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	9	6/2/2022	NON-COMPETING CONTINUATION	$407,035
														Subtotal = $407,035

Issue Date FY: 2021 ( Subtotal = $524,489 )
2021	2021	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	8	4/29/2021	NON-COMPETING CONTINUATION	$524,489
														Subtotal = $524,489

Issue Date FY: 2020 ( Subtotal = $451,499 )
2020	2020	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	7	4/28/2020	NON-COMPETING CONTINUATION	$451,499
														Subtotal = $451,499

Issue Date FY: 2019 ( Subtotal = $481,490 )
2019	2019	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	002	6	5/21/2019	NON-COMPETING CONTINUATION	$481,490
2019	2018	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	001	5	1/29/2019	COMPETING CONTINUATION	$2,425
2019	2016	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	4	1/29/2019	EXTENSION WITH OR WITHOUT FUNDS	-$2,425
														Subtotal = $481,490

Issue Date FY: 2018 ( Subtotal = $412,063 )
2018	2018	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	5	5/22/2018	COMPETING CONTINUATION	$412,063
														Subtotal = $412,063

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	001	4	11/15/2016	EXTENSION WITH OR WITHOUT FUNDS	$81,478
2017	2015	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	3	11/15/2016	NON-COMPETING CONTINUATION	-$81,478
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $316,967 )
2016	2016	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Allergy and Infectious Diseases Research	000	4	5/13/2016	EXTENSION WITH OR WITHOUT FUNDS	$316,967
														Subtotal = $316,967

Issue Date FY: 2015 ( Subtotal = $318,155 )
2015	2015	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Allergy and Infectious Diseases Research	000	3	5/12/2015	NON-COMPETING CONTINUATION	$318,155
														Subtotal = $318,155

Issue Date FY: 2014 ( Subtotal = $314,821 )
2014	2014	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Allergy and Infectious Diseases Research	000	2	5/19/2014	NON-COMPETING CONTINUATION	$314,821
														Subtotal = $314,821

Issue Date FY: 2013 ( Subtotal = $286,435 )
2013	2013	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Allergy and Infectious Diseases Research	000	1	5/28/2013	NEW	$286,435
														Subtotal = $286,435

Grand Total All Awards = $3,512,954

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Determination of the genetic basis for B. burgdorferi mammalian infectivity

Award Number: R01AI099094

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: 06/01/2013

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer