2. Academic Validation
  3. An enoyl-ACP reductase inhibitor, NITD-916, expresses anti- Mycobacterium abscessus activity

An enoyl-ACP reductase inhibitor, NITD-916, expresses anti- Mycobacterium abscessus activity

  • Antimicrob Agents Chemother. 2025 Jul 2;69(7):e0024925. doi: 10.1128/aac.00249-25.
Yaping Jia 1 2,  Junsheng Fan 1 2,  Zhili Tan 1 2,  Anqi Li 1 2,  Siyuan He 1 2,  Yani Lin 1 2,  Juan Li 1 2,  Zhemin Zhang 1 2,  Bing Li 1 2,  Haiqing Chu 1 2 3
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine,Tongji University, Shanghai, China.
  • 2 School of Medicine, Tongji University, Shanghai, China.
  • 3 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine,Tongji University, Shanghai, China.
PMID: 40407337 DOI: 10.1128/aac.00249-25
Abstract

Antibiotic therapy for Mycobacterium abscessus infections is challenging due to resistance of the organism to many clinically available antimicrobials. Here, the efficacy of NITD-916, an enoyl-ACP reductase inhibitor, in preventing M. abscessus growth in vitro and in vivo is demonstrated. The minimal inhibitory concentrations (MICs) of NITD-916 for 12 non-tuberculosis mycobacteria (NTM) reference strains and a collection of 194 clinical M. abscessus isolates were determined using the broth microdilution method. Compatibility of NITD-916 with 10 clinically important Antibiotics was ascertained by checkerboard assay. The activity of NITD-916 against M. abscessus growing in cultured macrophages was also evaluated. Finally, the potency of NITD-916 in vivo was determined in a mouse model that mimicked an acute pulmonary M. abscessus Infection. NITD-916 was bacteriostatic for M. abscessus replicating in vitro, expressing a MIC50 of 0.125 mg/L and a MIC90 of 1 mg/L against the screened clinical isolates. Furthermore, NITD-916 synergized with clarithromycin in treating 2 out of 5 subsp. massiliense strains. NITD-916 was active against M. abscessus replicating in both cultured macrophages and infected mice. The administration of 100 mg/kg NITD-916 for 14 days resulted in a 5.6 log10 colony-forming units (CFUs) reduction in the Bacterial load in mouse lung tissue. NITD-916 is active against M. abscessus in vitro and in vivo and may be used potentially to treat M. abscessus diseases.

Keywords

Mycobacterium abscessus; NITD-916; NTM; antimicrobial activity; enoyl-ACP reductase inhibitor.

Figures
Products