Advances in antibacterial agents for Mycobacterium fortuitum

Mycobacterium fortuitum is an emerging human pathogen, characterized by an increase in prevalence and antibacterial resistance over the years, highlighting the need for the development of new drugs against this rapidly growing nontuberculous mycobacterium (NTM). To support this crusade, this review summarizes findings from the past two decades concerning compounds with antimycobacterial activity against M. fortuitum. It identifies the most promising and effective chemical frameworks to inspire the development of new therapeutic alternatives for infections caused by this microorganism. Most compounds effective against M. fortuitum are synthetic, with macozinone, featuring a 2-piperazine-benzothiazinone framework, standing out as a notable drug candidate. Among natural products, the polyphenolic polyketide clostrubin and the sansanmycin peptide analogs have shown efficacy against this NTM. Some compounds' mechanisms of action on M. fortuitum have been studied, including NITD-916, which acts as an enoyl-acyl carrier protein reductase inhibitor, and TBAJ-5307, which inhibits F-ATP synthase. Moreover, this review discusses the pathogenic molecular mechanisms and potential therapeutic targets within this mycobacterium.