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Gene & Protein in Disease Phage therapy for Mycobacterium infections

guinea pigs. The bacteriophage D29 has demonstrated the there are about 10 phage infections per second, with new
23
capability to infect M. tuberculosis and has been effectively generations emerging every few days. Given these data, it is
utilized in the diagnosis and treatment of TB. 88,89 In not surprising that phage populations are highly diverse. 40
general, mycobacteriophages offer potential as tools to Mycobacteriophages are viruses that infect mycobacterial
address drug-resistant TB, but further investigation and hosts and are of particular interest for two primary reasons.
advancement are necessary to fully realize their clinical First, the abundance of complete mycobacteriophage
potential. Despite persistent challenges in treating drug-
resistant TB, phage therapy, as an innovative therapeutic genome sequences suggests a high level of diversity,
approach, presents a ray of hope in addressing the issue of offering valuable insights into phage genomic diversity
drug resistance in M. tuberculosis. With continued research and the evolutionary mechanisms responsible for this
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and practical application, phage therapy is anticipated diversity. Second, mycobacteriophages offer a rich array
to emerge as an efficacious method for addressing TB of tools for developing genetic systems for hosts, including
and other drug-resistant infections, thereby making a M. tuberculosis, the pathogen responsible for human TB,
significant contribution to the global prevention and and present novel strategies for diagnosing, preventing,
treatment of TB. and treating TB. Furthermore, the discovery and genomic
characterization of new mycobacteriophages provide
Nowadays, mycobacteriophage therapy alone/in an effective platform for introducing authentic research
cocktails or in combination with antibiotics has opened experiences to inexperienced scientists. 100
90
up new horizons for the treatment of infections caused
by pathogenic mycobacteria 91-93 (Table 2). Furthermore, Phage therapy is a treatment modality that employs
engineered shuttle plasmids have been employed for specific phage viruses to target and eliminate bacteria.
diagnostic purposes in the context of mycobacteriophage Depending on how phages are used, phage therapy can be
infection of M. tuberculosis strains. Notably, DS6A and divided into several types. One approach involves using
TM4 have been utilized in various investigations to individual phages, which may have limitations due to
produce shuttle plasmids. 26 their narrow host spectrum and potential for inadequate
immune response. Another approach is phage cocktail
7. Discussion therapy, where a combination of multiple phages is used
Bacteriophages are a type of virus that infects and causes to address bacterial infections, with the objective of
the lysis of bacteria, exhibiting their ability to selectively leveraging diverse phages to augment therapeutic efficacy,
target and eliminate their host bacteria. They are prevalent particularly against MDR strains. The process of preparing
both in natural environments and within the human a phage cocktail entails screening and isolating numerous
body. Essentially, wherever bacteria exist, bacteriophages phages from the environment and then combining them
are also present. The estimated number of phages in the to create a therapeutic mixture. Each phage exhibits
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biosphere is approximately 10 31,97-99 Originating around specificity and can be directed against distinct bacterial
3 billion years ago, phage populations are dynamic and strains. Utilizing multiple phages concurrently enables
continually evolving. They persistently infect host bacteria, the provision of wider protection against diverse bacterial
replicate, and replenish their numbers. It is estimated that types. The advantage of this approach is that it prevents

Table 2. Examples of phage therapy in mycobacterial infections
Patients Underlying conditions Causative agent Phages used References
A total of 20 patients Cystic fibrosis, scleroderma, M. abscessus, M. chelonae, BPs∆33HTH_HRM10, Muddy, ZoeJ∆45, Itos, 94,95
with drug-resistant arthritis, and mendelian Mycobacteroides avium, and BPs∆33HTH_HRMGD03, D29_HRMGD40,
mycobacterial disease susceptibility to mycobacterial Bacillus Calmette-Guerin Fionnbharth∆43∆45, and Fred313cpm∆33
disease
A 26-year-old patients Cystic fibrosis and M. abscessus BPsΔ33HTH_HRM10 and D29_HRMGD40 77
bronchiectasis
An 81-year-old patients Bronchiectasis M. abscessus Muddy, BPs33ΔHTH_HRM10, and ZoeJΔ45 96
A 15-year-old patient Cystic fibrosis and bilateral lung M. abscessus Muddy, BPs33ΔHTH_HRM10, and ZoeJΔ45 76
transplant
A 56-year-old patient Nodular lesions, seronegative M. chelonae Muddy 78
arthritis, and peripheral
neuropathy
Abbreviations: M. abscessus: Mycobacteroides abscessus, M. chelonae: Mycobacteroides chelonae.

Volume 3 Issue 3 (2024) 8 doi: 10.36922/gpd.2935