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Gene & Protein in Disease Phage therapy for Mycobacterium infections

the development and production of phage therapies, on the degree of shared nucleotides found in their genomic
necessitating extensive time and resources to generate sequences. 35,39,41,42 Twenty of these clusters are subdivided
adequate phage quantities for treatment. Another notable into two to 11 sub-clusters, depending on nucleotide
obstacle is the potential emergence of bacterial resistance sequence similarity. These sub-clusters further categorize
to mycobacteriophages, given that mycobacteria form similar phages into smaller groups within the same cluster
biofilms, offering a protective environment that impedes through a more comprehensive genomic comparison and
phage targeting and infection. 30 analysis. The majority of mycobacteriophages (n = 322)
fall within cluster A, which is further subdivided into 18
Research efforts are underway to address the challenges
in the application of bacteriophages as therapeutic agents. sub-clusters (A1-A14 and A16-A19). Cluster A is the most
One promising approach is the development of synthetic extensive grouping of mycobacteriophages, comprising the
phages, which can be engineered to have enhanced more conventional mycobacteriophages with comparable
stability, efficacy, and specificity against bacterial targets. host ranges and genome structures. The phages within this
In addition, efforts are being made to expand the phage cluster are typically characterized by their mild nature and
affiliation with the Siphonariidae family. They possess tails
library, with the aim of ensuring a broader spectrum of of short to medium length, with genomes featuring 3’ ends
activity against various mycobacterial strains, including and structural genes located in the left arm, transcribed in
drug-resistant forms. These research endeavors have the the forward direction. Integrases are commonly situated
potential to significantly improve the clinical application near the midpoint of the genome, whereas early genes are
and effectiveness of bacteriophage therapy for the treatment
of bacterial infections. 32 often transcribed from the reverse strand and located in the
right arm of the genome. Among the mycobacteriophages
4. The cluster and subcluster of in Cluster A, L5 was the first to be sequenced. Another
mycobacteriophages prominent member of Cluster A is D29, identified by
Froman et al. in 1954, which has a gene length of
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At present, over 2000 mycobacteriophages have 49,127 bp and a guanine-cytosine (GC) content of 63.5%.
been identified, and their genetic sequences have Cluster B comprises several prevalent mycobacteriophages,
been determined. The majority of these phages including Bcep781, K139, and KS5. These phages exhibit
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have been isolated from Mycobacterium smegmatis distinct genome structure and host range compared to those
mc2155. 36-38 The genetic material of these phages is classified in Cluster A. Typically, the phages within this cluster are
as double-stranded DNA, and the majority of them exhibit characterized as virulent. Cluster C is a substantial grouping
a tailed morphology characteristic of phages. Comparative comprising diverse mycobacteriophages, including φE125,
genomic analyses focusing on the nucleotide and gene TW1, and SfV. The phages within this cluster are typically
content levels indicate that despite sharing a common characterized by their virulence. Cluster D, though smaller,
host and the potential for genetic exchange, these phages includes mycobacteriophages with distinctive genomic
exhibit significant diversity. As per the classification configurations, including JG024, phiEa1h, and TW2.
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of mycobacteriophages by Hatfull and Hendrix, a Cluster E is another substantial assemblage (n = 52), but
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bacteriophage family is considered identical if the span it does not have any sub-clusters. Cluster F is a prevalent
of nucleotide sequence similarity encompasses more than category among mycobacteriophages, comprising a total of
50% of the entire genome and if the bacteriophage exhibits 220 phage species, 207 of which are in the F1 sub-cluster.
comparable genomic structure. However, some phages lack Within Cluster F, DS6A is categorized as a solitary phage.
homologous sequences and are, thus, classified as orphan According to the Actinomycete database (https://phagesdb.
families. org/), mycobacteriophage genomes range in size from 41
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Traditional methods for categorizing mycobacteriophages to 165 kb and have a GC content between 50% and 70%.
primarily rely on morphological features and the range The phage genomes within cluster F1 vary in length from
of hosts they infect. However, with advances in genome 52,141 bp to 61,164 bp, with gene counts ranging from 88
sequencing technology, classification methods based on to 113.
genomic data have become more prevalent, offering a The aforementioned are just a few examples of
more precise depiction of phage diversity. One commonly common cluster classifications, and as more data on phage
used genome-based classification system is the phage genomes are gathered, it is likely that additional phage
comparative genomics groups (clusters) system, classifications will be identified. There may be genomic
developed by the Phages DB project. Contemporary characteristics and functions that are shared among
mycobacteriophages can be categorized into 31 clusters different taxonomic groups, but there are also distinct
(A-Z, AA, AB, AC, AD, and AE) and seven singletons based differences. It is important to point out that genomic-based

Volume 3 Issue 3 (2024) 4 doi: 10.36922/gpd.2935