Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Harnessing polymicrobial interactions in the catheterized urinary tract to identify novel inhibitors of Proteus mirabilis urease activity

Award Number: F30DK136213
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

Group Awards By:

View Award Description

Harnessing polymicrobial interactions in the catheterized urinary tract to identify novel inhibitors of Proteus mirabilis urease activity - Project Summary Catheter-associated urinary tract infection (CAUTI) is the leading cause of secondary nosocomial bloodstream infections. Urease-producing organisms such as Proteus mirabilis are common causes of CAUTI and associated with numerous complications. Urease hydrolyzes urea to ammonia, which raises the urine pH and causes precipitation of ions into crystals, ultimately leading to catheter encrustation and blockage and urinary stone formation and increasing the risk of bacteremia, sepsis and death. The only urease inhibitor approved by the Food and Drug Administration (FDA), acetohydroxamic acid (AHA), shows efficacy in preventing urinary stone formation but has severe side effects that limit its clinical use. Therefore, alternative strategies are needed for targeting bacterial urease activity to prevent catheter encrustation and stone formation. In patients with long-term indwelling catheters, CAUTI is often polymicrobial. As demonstrated in our prior publications and preliminary data, we found that common constituents of polymicrobial CAUTI secrete molecules that modulate P. mirabilis urease activity and infection severity. We therefore performed untargeted global metabolomics analysis on cell-free supernatants of urease-modulating bacterial strains and identified 36 candidate urease dampening metabolites. We validated the activity of four compounds: histamine (CAS 51-45- 6), leucylglycine (CAS 686-50-0), phenylpyruvate (CAS 156-06-9) and imidazole lactate (CAS 14403-45-3). Our preliminary data suggests that leucylglycine and imidazole lactate dampen urease activity, at least in part, by acting directly on the urease active site. In contrast, histamine and phenylpyruvate appear to indirectly inhibit urease activity through an uncharacterized mechanism. The goal of this NRSA F30 proposal is to determine the mechanism of action of urease modulation and conduct pre-clinical assessment of the therapeutic potential of these dampening compounds. Aim 1 will determine the mechanism of indirect urease modulation for histamine and phenylpyruvate and explore whether compounds of different mechanisms of action have synergistic effects on urease activity when administered in combination against a panel of urease- producing pathogens. Aim 2 will assess the translational potential of dampening compounds for preventing Foley catheter encrustation, crystalline biofilm formation, and blockage. The experiments outlined in this proposal will provide a framework for harnessing polymicrobial interactions for drug discovery and the development of novel therapeutics to prevent CAUTI associated morbidity and mortality. This work will take place at the Jacobs School of Medicine and Biomedical Sciences in the laboratory of Dr. Chelsie Armbruster, who is an expert in CAUTI and microbial pathogenesis research. The training plan is tailored for my development as a physician-scientist in the field of infectious disease, and includes mentoring by successful physician-scientists and clinical preceptorships in infectious disease and internal medicine.


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 = $58,678 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	4/1/2026	NON-COMPETING CONTINUATION	$576
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	3/30/2026	NON-COMPETING CONTINUATION	$57,538
2026	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/18/2026	NON-COMPETING CONTINUATION	$564
														Subtotal = $58,678

Issue Date FY: 2025 ( Subtotal = $34,680 )
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/14/2025	NON-COMPETING CONTINUATION	$34,680
														Subtotal = $34,680

Issue Date FY: 2024 ( Subtotal = $34,599 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/10/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/25/2024	NON-COMPETING CONTINUATION	$33,319
														Subtotal = $34,599

Issue Date FY: 2023 ( Subtotal = $37,254 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/24/2023	NEW	$37,254
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	3/24/2023	NEW	$0
														Subtotal = $37,254

Grand Total All Awards = $165,211

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Harnessing polymicrobial interactions in the catheterized urinary tract to identify novel inhibitors of Proteus mirabilis urease activity

Award Number: F30DK136213

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer