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Spore germination pathway in Clostridioides difficile and its pharmacological intervention

Award Number: R01AI178776
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: 08/09/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2025
AWARD TERMINATION DATE: 04/18/2025

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Spore germination pathway in Clostridioides difficile and its pharmacological intervention - ABSTRACT Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the gut of patients treated with broad-spectrum antibiotics. A challenge in treating C. difficile infection (CDI) is the production of spores that germinate to active vegetative cells in response to host bile acids. The normal gut microflora typically prevents colonization of C. difficile. Gut microflora dysbiosis as a consequence of treatment with broad-spectrum antibiotics causes recurrence of CDI in 25% of patients, for which spore germination is an instigator. There are no antibiotics for the treatment of multiple recurrent CDI, leading to 11,500 annual deaths in the United States. CDI is the deadliest of the five bacterial urgent threats. Understanding the process of spore germination is key to elucidating the basis for recurrent CDI. If spore germination could be prevented, the nefarious cycles of CDI can be interrupted. We disclose the discovery of the oxadiazoles with bactericidal activity against C. difficile vegetative cells, of which certain oxadiazoles also inhibit spore germination. This grant proposal is outlined in three Specific Aims. We disclose our efforts in elucidation of the details of the spore-germination pathway (Specific Aim 1). We have proposed experiments to demonstrate that inhibition of spore germination is at the root of recurrence of CDI (Specific Aim 2). Furthermore, we outline our efforts to intervene pharmacologically in recurrent CDI by inhibition of spore germination (Specific Aim 3).


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	2024	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	1	11/21/2025	TERMINATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	1	4/18/2025	TERMINATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $770,512 )
2024	2024	UNIVERSITY OF NOTRE DAME DU LAC	836 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Allergy and Infectious Diseases Research	000	1	8/9/2024	NEW	$770,512
														Subtotal = $770,512

Grand Total All Awards = $770,512

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Spore germination pathway in Clostridioides difficile and its pharmacological intervention

Award Number: R01AI178776

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: 08/09/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2025

AWARD TERMINATION DATE: 04/18/2025

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