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

Antibiotic tolerance by multidrug resistant uropathogenic Escherichia coli during quiescence

Award Number: R21AI156574
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: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2024

Group Awards By:

View Award Description

Antibiotic tolerance by multidrug resistant uropathogenic Escherichia coli during quiescence - Project Summary / Abstract Clinical uropathogenic Escherichia coli (UPEC) strains, which are the causative agent of most urinary tract infections (UTIs), form quiescent intracellular reservoirs in the host where they can evade the action of antibiotics. We recently found that many clinical UPEC isolates also enter a non-proliferative quiescent, but viable, state in vitro that is quorum-dependent and reversed by specific signals, including peptidoglycan fragments (1). Of the 145 UPEC strains tested, 51 entered quiescence in vitro (1), including the well-studied virulent strain CFT073 and the pandemic strain JJ1886, a group B2 multi antibiotic resistant ST131/H30-Rx blood isolate from a patient with fatal urosepsis. Here, we will determine if quiescent UPEC cells formed in vitro are capable of evading antibiotics across major antibiotic classes as a result of entering the quiescent state. Our in vitro model will lay the foundational groundwork to rapidly determine if a clinical UPEC isolate enters quiescence and if so which classes of antibiotics are effective at killing those quiescent cells. We propose to uncover the antibiotic tolerance features associated with quiescent UPEC and test strategies to induce proliferation, which may overcome antibiotic tolerance. In Aim 1, we will elucidate the bactericidal and bacteriostatic effects of major antibiotic classes on growing and quiescent cells of clinically significant UTIs, including JJ1886, a multidrug resistant ST131 strain, and CFT073, an ST73 strain. We will determine if antibiotic tolerance is reversed upon stimulating proliferation of quiescent cells by addition of external proliferation signals in vitro. In Aim 2, we will test if UPEC cells become quiescent upon invasion of cultured epithelial cells and if proliferants modify the antibiotic tolerance and susceptibility profiles of bacteria associated with intracellular reservoirs. SIGNIFICANCE: Most UTIs are caused by UPEC and many patients experience recurrent infections. The bacteria associated with recurrent infections are thought to survive antibiotic treatment by entering a quiescent state in bladder epithelial cells, which allows them to resume growth upon release into urine at a later time. The studies proposed here are straightforward yet they may have significant implications for treating recurrent UTIs. We will identify if quiescent UPEC cells have tolerances to specific classes of antibiotics, and susceptibility to others, whether this translates to the same or different tolerances and susceptibilities in intracellular reservoirs, and whether quiescent cell tolerance in intracellular reservoirs can be modified by addition of specific proliferants. Therefore, the studies proposed here may elucidate new therapeutic strategies to prevent both antibiotic tolerance in UPEC and recurrent UTIs caused by UPEC.


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: 2025 ( Subtotal = -$1,010 )
2025	2022	UNIVERSITY OF RHODE ISLAND	75 LOWER COLLEGE RD RM 103	KINGSTON	RI	02881	WASHINGTON	USA	Allergy and Infectious Diseases Research	000	2	10/29/2024	NON-COMPETING CONTINUATION	-$1,010
														Subtotal = -$1,010

Issue Date FY: 2022 ( Subtotal = $196,875 )
2022	2022	UNIVERSITY OF RHODE ISLAND	75 LOWER COLLEGE	KINGSTON	RI	02881	WASHINGTON	USA	Allergy and Infectious Diseases Research	000	2	3/11/2022	NON-COMPETING CONTINUATION	$196,875
														Subtotal = $196,875

Issue Date FY: 2021 ( Subtotal = $231,382 )
2021	2021	UNIVERSITY OF RHODE ISLAND	75 LOWER COLLEGE	KINGSTON	RI	02881	WASHINGTON	USA	Allergy and Infectious Diseases Research	000	1	4/1/2021	NEW	$231,382
														Subtotal = $231,382

Grand Total All Awards = $427,247

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Antibiotic tolerance by multidrug resistant uropathogenic Escherichia coli during quiescence

Award Number: R21AI156574

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: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer