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

Discovering antimicrobials acting against MDR pathogens

Award Number: R01AI170962
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: 09/02/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2026

Group Awards By:

View Award Description

Discovering antimicrobials acting against MDR pathogens - Abstract We are experiencing an antimicrobial resistance crisis (AMR), a direct result of a decline in antibiotic discovery. The WHO designated a list of priority pathogens, and of these, MDR Gram- negative Enterobacteriaceae (E. coli, S. typhimurium, Klebsiella pneumoniae, Enterobacter), Pseudomonas aeruginosa, and Acinetobacter baumannii) are of “critical priority”. These pathogens are the focus of the present proposal aimed at developing a platform for efficient discovery of novel antimicrobials. The field once enjoyed a golden era of discovery, fueled mainly by screening of soil actinomycetes. All major classes of broad-spectrum antibiotics active against Gram-negative pathogens were discovered by the 1960s. Overmining of actinomycetes resulted in the collapse of the discovery platform. Novel antibiotics discovered since then only act against Gram-positive species. We developed methods to access a broader range of bacteria, with a focus on uncultured species that make up 99% of total biodiversity. A number of novel compounds came from this source, including teixobactin, representing a new class of cell- wall acting compounds without detectable resistance (Ling et al., 2015). Teixobactin is undergoing IND-enabling studies; it is also a narrow-spectrum compound. We propose to develop a platform for efficient discovery of novel antimicrobials. The main problem is the enormous background of toxic, and to a lesser extent, known compounds. We hypothesize that the bottleneck of dereplication can be resolved by differential screening that detects the presence of a promising compound prior to dereplication. Using this approach, we recently discovered darobactins that have a novel scaffold and target the essential outer membrane protein BamA (Imai et al., 2019), and several additional novel compounds. In the proposed project, we will develop an ultra-high throughput screen based on encapsulating producing bacteria together with different fluorescently labeled reporters in microdroplets created in a microfluidics device. Our preliminary data show that sorting droplets can be performed at a rate of 106 a day, and leads to detection of producers of desirable antimicrobials. We will evaluate several modalities of this screen, aimed at discovering selective as well as broad-spectrum compounds acting against Gram-negative bacteria; and anti-persister compounds. The platform is likely to be of use to the field of antibiotic discovery. Leads that come out of this screen will be evaluated in vitro and in animal models of infection. Novel leads that come out of this project will be ready to enter IND-enabling studies.


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 = $1,095,522 )
2025	2025	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	8/12/2025	NON-COMPETING CONTINUATION	$1,095,522
														Subtotal = $1,095,522

Issue Date FY: 2024 ( Subtotal = $1,095,522 )
2024	2024	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	8/1/2024	NON-COMPETING CONTINUATION	$1,095,522
														Subtotal = $1,095,522

Issue Date FY: 2023 ( Subtotal = $1,141,522 )
2023	2023	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	8/8/2023	NON-COMPETING CONTINUATION	$1,141,522
														Subtotal = $1,141,522

Issue Date FY: 2022 ( Subtotal = $1,136,522 )
2022	2022	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	9/2/2022	NEW	$1,136,522
														Subtotal = $1,136,522

Grand Total All Awards = $4,469,088

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Discovering antimicrobials acting against MDR pathogens

Award Number: R01AI170962

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: 09/02/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer