A Review on Mycobacteriophages: From Classification to Applications

Mycobacterial infections are a group of life-threatening conditions triggered by fast- or slow-growing mycobacteria. Some mycobacteria, such as Mycobacterium tuberculosis, promote the deaths of millions of lives throughout the world annually. The control of mycobacterial infections is influenced by the challenges faced in the diagnosis of these bacteria and the capability of these pathogens to develop resistance against common antibiotics. Detection of mycobacterial infections is always demanding due to the intracellular nature of these pathogens that, along with the lipidenriched structure of the cell wall, complicates the access to the internal contents of mycobacterial cells. Moreover, recent studies depicted that more than 20% of M. tuberculosis (Mtb) infections are multi-drug resistant (MDR), and only 50% of positive MDR-Mtb cases are responsive to standard treatments. Similarly, the susceptibility of nontuberculosis mycobacteria (NTM) to first-line tuberculosis antibiotics has also declined in recent years. Exploiting mycobacteriophages as viruses that infect mycobacteria has significantly accelerated the diagnosis and treatment of mycobacterial infections. This is because mycobacteriophages, regardless of their cycle type (temperate/lytic), can tackle barriers in the mycobacterial cell wall and make the infected bacteria replicate phage DNA along with their DNA. Although the infectivity of the majority of discovered mycobacteriophages has been evaluated in non-pathogenic M. smegmatis, more research is still ongoing to find mycobacteriophages specific to pathogenic mycobacteria, such as phage DS6A, which has been shown to be able to infect members of the M. tuberculosis complex. Accordingly, this review aimed to introduce some potential mycobacteriophages in the research, specifically those that are infective to the three troublesome mycobacteria, M. tuberculosis, M. avium subsp. paratuberculosis (MAP), and M. abscessus, highlighting their theranostic applications in medicine.