A Review on Mycobacteriophages: From Classification to Applications

Abstract

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 lipid-enriched 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.

Genome sequence of the lytic bacteriophage Alucard, a cluster EE actinophage

“…Actinobacteria phages are increasingly being developed as therapeutics for treating bacterial infections ( 1 ). To shed more light on the ecology and diversity of actinobacteriophages, here we report on bacteriophage Alucard, isolated using Microbacterium foliorum (NRRL B-24224), that contains no detectable prophages or CRISPR systems and is therefore ideal as an isolation host ( 2 ).…”

A novel LysinB from an F2 sub-cluster mycobacteriophageRitSun

“…The role of mycobacteriophages and their derived endolysins in human therapy has gained attention, especially in the last few years when mycobacteriophages were used to treat drug-resistant NTM infections [25,26]. Phages and endolysins can also play an important role in potentially shortening the treatment regimen of TB/NTM infections [9,27]. The mycobacterial cell envelope is more elaborate when compared to Gram-positive and Gram-negative bacteria; it contains an additional mycolylarabinogalactan layer, which forms an ester linkage with the peptidoglycan.…”

Phenotypic Characterization and Comparative Genomic Analyses of Mycobacteriophage WIVsmall as A New Member Assigned to F1 Subcluster

“…Based on the 2022 World Health Organization (WHO) report on tuberculosis (TB), the proportion of multi-drug resistant cases was estimated as being 20% in 2021, and almost 43% of MDR-TB cases were treated between 2018 and 2021 [ 12 ]. Mycobacteriophages, either in isolation or as a cocktail, or as part of a synergistic therapy with antibiotics, have potential in the treatment of mycobacterial infections [ 13 ]. It is reported that 20 patients with antibiotic-refractory mycobacterial infections received treatment with a mycobacteriophage cocktail [ 14 ].…”

“…Additionally, Jessica S. Little and her team reported a case of a 56-year-old patient with a refractory disseminated cutaneous Mycobacterium chelonae infection, who received mycobacteriophage therapy, and experienced a significant improvement in their skin lesions [ 15 ]. Mycobacteriophages can also be utilized as a tool for engineering shuttle plasmids to detect drug-resistant M. tuberculosis strains, including DS6A and TM4-based shuttle plasmids [ 13 , 16 ].…”