Zebrafish Models for Drug Discovery and Therapeutic Validation against Non-Tuberculous Mycobacteria

The incidence of non-tuberculous mycobacteria (NTM) is increasing globally, often surpassing the incidence of new tuberculosis (TB) cases in developed countries. Most NTM are environmental organisms; however, there are a number of opportunistic and pathogenic species that can cause severe infections in animals and humans. Many NTM are intrinsically resistant to anti-TB therapies and are incredibly difficult to treat, resulting in poor treatment outcomes for these patients. Recent advances in preclinical animal models such as the zebrafish models have led to the discovery of highly active antimicrobial and host-directed therapies (HDTs) targeting NTM infections that can be applied to treat human infections. Here, we summarize recent progress and technological advancements in the discovery and development of antimicrobial drugs and HDTs that have been applied to NTM zebrafish infection models. We highlight the future directions for this increasingly applicable animal model for the discovery of next-generation therapies to treat NTM diseases.