Exploring the next "phage" of treating non-tuberculous mycobacterial infections

Non-tuberculous mycobacteria (NTM) can present a serious clinical threat due to their resistance to conventional antibiotics and their ability to cause persistent infections. As antimicrobial resistance (AMR) represents one of the most significant global health threats, mycobacteriophages (MPs)-viruses that specifically target mycobacterial species-are emerging as a promising therapeutic addition or alternative. This review explores the biological characteristics, therapeutic mechanisms, and clinical potential of MPs, with a primary focus on their use against NTM infections. Based on data from in vitro studies, animal models, and human compassionate-use cases, we highlight the mycobactericidal efficacy of MPs as well as their potential to complement antibiotic treatment regimens. However, there are key challenges that need to be addressed to implement MPs as therapeutics-such as limited host range, immune response interference, MP resistance, and intracellular delivery barriers. The implementation of MP banks, standardized regulatory protocols, and approved clinical trials is highly essential for MP therapy to transition smoothly into the healthcare sectors. By carrying out coordinated scientific, regulatory, and clinical efforts, MP-based therapy holds a promising potential in combating antibiotic-resistant NTM infections.