Project Grant R01AI195600

The National Institute of Allergy and Infectious Diseases awarded Beth Israel Deaconess Medical Center, Inc. $844,925 on August 17, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to design apramycin analogs targeting resistance in gram-negative pathogens.

The project focuses on structure-guided derivatization of apramycin to block inactivation by aminoglycoside-modifying enzymes and extend activity spectrum to multidrug-resistant gram-negative ESKAPE pathogens—carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa—while optimizing ribosomal selectivity and minimizing toxicity. Apramycin retains activity against strains expressing ribosomal methylases that render clinically approved aminoglycosides ineffective and avoids the nephrotoxic and ototoxic side effects that have limited use of other aminoglycosides. The work proposes combinatorial modifications to apramycin's 4-aminoglucose and 2-deoxystreptamine rings to develop highly selective, potent analogs with broad in vitro and in vivo activity.

Performance occurs in Boston, Massachusetts. The period of performance runs through July 31, 2031. The assistance type is a Project Grant, supporting investigator-initiated research at a nonprofit academic medical center.