Sunday, August 31, 2025 8/31/2025

Differential Effects of TcdB1 and TcdB2 in C. difficile disease

Award Number: R01AI119048
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: 08/07/2015
PERIOD OF PERFORMANCE END DATE: 01/31/2025

Group Awards By:

View Award Description

Differential Effects of TcdB1 and TcdB2 in C. difficile disease - ABSTRACT The most recent reports indicate Clostridioides difficile is the cause of over 400,000 cases of gastrointestinal illness and nearly 30,000 deaths annually. A major factor in the virulence of C. difficile is TcdB, an intracellular bacterial toxin that glucosylates small GTPases in targeted cells. Our studies focus on determining the critical differences in TcdB1 and TcdB2, the two major variants of TcdB. TcdB1 is produced by historical strains of C. difficile and TcdB2 is produced by hypervirulent/epidemic strains of C. difficile. Understanding how these two forms of TcdB, which share 92% identity, differ in critical steps in intoxication and immunogenicity provides insight into underlying differences in virulence between historical and epidemic strains of C. difficile. Several studies, including many from our group, have found that TcdB1 and TcdB2 differ in their interactions with target cells, tropism, cytotoxicity, and immunogenicity. The objective of our work is to identify and characterize the underlying molecular and cellular details of the factors accounting for these differences in TcdB1 and TcdB2 activity. To continue this line of investigation, three specific aims to i) Determine the underlying differences in the molecular mechanism of TcdB1 and TcdB2 receptor binding and cell penetration, ii) Determine if TcdB2 subverts antigen presentation and limits humoral immunity to co-administered vaccine antigen TcdB2Δ1769-1787, and iii) Construct and test strains of C. difficile expressing mutants of TcdB1 and TcdB2 will be pursued. These studies will provide further insight into the differences in TcdB1 and TcdB2, determine the contribution of TcdB to ineffective immune memory leading to relapse, and test hypotheses related to specific TcdB functional activities in the context of C. difficile infection. Overall, the findings from this work will enhance our understanding of C. difficile disease at multiple levels and provide information needed to prevent and treat this serious human illness.


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 = $432,300 )
2024	2024	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	001	10	5/23/2024	NON-COMPETING CONTINUATION	$43,230
2024	2024	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	10	1/11/2024	NON-COMPETING CONTINUATION	$389,070
														Subtotal = $432,300

Issue Date FY: 2023 ( Subtotal = $432,300 )
2023	2023	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	9	1/12/2023	NON-COMPETING CONTINUATION	$432,300
														Subtotal = $432,300

Issue Date FY: 2022 ( Subtotal = $432,300 )
2022	2022	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	8	1/10/2022	NON-COMPETING CONTINUATION	$432,300
														Subtotal = $432,300

Issue Date FY: 2021 ( Subtotal = $432,300 )
2021	2021	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	7	1/22/2021	NON-COMPETING CONTINUATION	$432,300
														Subtotal = $432,300

Issue Date FY: 2020 ( Subtotal = $432,300 )
2020	2020	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	6	2/3/2020	COMPETING CONTINUATION	$432,300
2020	2020	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	002	6	9/8/2020	COMPETING CONTINUATION	$54,040
2020	2019	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	001	5	9/8/2020	NON-COMPETING CONTINUATION	-$54,040
														Subtotal = $432,300

Issue Date FY: 2019 ( Subtotal = $370,000 )
2019	2019	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	5	1/15/2019	NON-COMPETING CONTINUATION	$370,000
														Subtotal = $370,000

Issue Date FY: 2018 ( Subtotal = $370,000 )
2018	2018	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	4	1/9/2018	NON-COMPETING CONTINUATION	$370,000
														Subtotal = $370,000

Issue Date FY: 2017 ( Subtotal = $370,000 )
2017	2017	UNIVERSITY OF OKLAHOMA	1100 N LINDSAY SCB 219	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	002	3	3/9/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$370,000
2017	2017	UNIVERSITY OF OKLAHOMA	1100 N LINDSAY SCB 219	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	3	1/13/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$370,000
2017	2017	UNIVERSITY OF OKLAHOMA	1100 N LINDSAY SCB 219	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	001	3	2/28/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$370,000
2017	2017	UNIVERSITY OF OKLAHOMA	1100 N LINDSAY SCB 219	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	004	3	5/1/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$52,720
2017	2016	UNIVERSITY OF OKLAHOMA	1100 N LINDSAY SCB 219	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	003	2	5/1/2017	NON-COMPETING CONTINUATION	-$52,720
														Subtotal = $370,000

Issue Date FY: 2016 ( Subtotal = $370,000 )
2016	2016	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	P.O. BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	2	1/21/2016	NON-COMPETING CONTINUATION	$370,000
														Subtotal = $370,000

Issue Date FY: 2015 ( Subtotal = $185,000 )
2015	2015	UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER	P.O. BOX 26901	OKLAHOMA CITY	OK	73190	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	1	8/7/2015	NEW	$185,000
														Subtotal = $185,000

Grand Total All Awards = $3,826,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Differential Effects of TcdB1 and TcdB2 in C. difficile disease

Award Number: R01AI119048

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: 08/07/2015

PERIOD OF PERFORMANCE END DATE: 01/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer