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

Structure-guided design of apramycin analogs to avoid resistance and enhance efficacy

Award Number: R01AI195600
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: 08/17/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

Group Awards By:

View Award Description

Structure-guided design of apramycin analogs to avoid resistance and enhance efficacy - Project Summary New antimicrobials are urgently needed to address the emergence of drug resistance in gram-negative pathogens. Apramycin is an unusual, glycosylated aminocyclitol that has broad-spectrum activity against carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii, and Pseudomonas aeruginosa. These pathogens are currently often untreatable or treatable only with toxic antimicrobials. Therefore, the CDC now categorizes such organisms in their top antibiotic resistance threat level. In contrast to clinically approved aminoglycosides including plazomicin, the apramycin scaffold retains activity against strains expressing widely circulating ribosomal methylases that are found at high frequency in NDM-1 carbapenemase-producing strains. Importantly, apramycin itself does not appear to have significant nephrotoxic and ototoxic side effects that have limited clinical use of other aminoglycosides. Indeed, there is only a single circulating aminoglycoside modifying enzyme (AME) in gram-negatives, present in ~30% of CRE strains, (extremely rare to absent in A. baumannii and P. aeruginosa), that inactivates APR through acetylation at the C-3 amine position in the 2-deoxystreptamine (2-DOS) ring. MICs in A. baumannii and P. aeruginosa are relatively elevated based on action of identified RND efflux pumps. Based on the underlying compelling properties of apramycin, we propose to address the hypothesis that combinatorial derivatization of apramycin's 4-aminoglucose and 2-DOS rings can block inactivation by AME, thereby extending activity spectrum broadly to multidrug-resistant gram-negative ESKAPE pathogens, while optimizing discriminatory interactions with the bacterial ribosome. Together, our goal will be to develop highly selective, potent, non-toxic apramycin analogs with broad in vitro activity spectrum and compelling in vivo activity.


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 = $844,925 )
2026	2026	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	8/17/2026	NEW	$844,925
														Subtotal = $844,925

Grand Total All Awards = $844,925

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Structure-guided design of apramycin analogs to avoid resistance and enhance efficacy

Award Number: R01AI195600

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: 08/17/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer