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Gene & Protein in Disease Phage therapy for Mycobacterium infections

comprehend the underlying mechanisms of resistance to thereby confirming its ability to effectively kill the
phage therapy to mitigate the occurrence of phage resistance. bacterium. Furthermore, LysB shows potential as a viable
Research has demonstrated that the removal of TPP results therapeutic option for promptly decreasing the M. abscessus
in resistance to phage attachment and subsequent infection. burden in the lungs of individuals with cystic fibrosis.
Transposon mutagenesis experiments indicate that the
primary mechanism of phage resistance is the deletion of 6. The application of mycobacteriophage
TPP. TPP is a type of glycolipid that is found within the therapy in clinical settings
cellular membrane, serving as a potential target for phage Mycobacterial infections present a clinical challenge in
recognition and attachment. TPP binds to mycolic acid to treatment due to their inherent resistance to conventional
form trehalolipid, which is considered to be one of the main antibiotics. Mycobacteriosis presents a significant challenge,
substances causing cell wall toxicity and a key factor in the posing a threat to the health and well-being of numerous
emergence of resistance in these bacteria. Bacteriophages individuals, including those with compromised immune
have the potential to achieve autonomy from TPP through systems, as well as animals, on an annual basis. The appearance
a single amino acid substitution in their tail spike protein. of mycobacteria that are resistant to multiple drugs has
Furthermore, the advancement of phage resistance can be prompted numerous inquiries. MDR-TB is characterized
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mitigated through the investigation and utilization of these by the bacteria’s resistance to the antibiotics isoniazid and
bacteriophages for therapeutic purposes. 62,63 rifampicin. Surveys conducted between 2009 and 2016
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5.4. Bactericidal activity of LysB against M. abscess revealed a 20% rise in the prevalence of MDR-TB among
individuals with M. tuberculosis infection. Research has
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Mycobacteria are a subset of Gram-positive bacteria indicated that M. tuberculosis possesses inherent resistance
characterized by a unique cell wall structure. In contrast to numerous antibiotics, potentially compromising the
to other Gram-positive bacteria, their outermost cell wall efficacy of these antibiotics against the pathogen. The
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layer consists of a lipid structure abundant in mycolic acid. mycobacteriophage, as a selective microbicide, presents a
Mycobacteriophage lyases are primarily composed of two promising alternative therapy for mycobacterial infections,
proteins, namely, cell wall lyase (lysin) and perforin (holin), particularly in cases involving MDR strains. The capacity
with LysA and LysB being the predominant forms of the of mycobacteriophages to penetrate the hydrophobic
former (Figure 2). The peptide chains of mycobacterial structures of the cell wall and invade mycobacteria suggests
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peptidoglycan are degraded by LysA, whereas the linkage their potential utility in the detection and management of
between mycobacterial acid and the peptidoglycan- infections resulting from pathogenic mycobacteria.
arabinogalactan complex is cleaved by LysB. Holin proteins
play a crucial role in the precise control of bacterial lysis In general, bacteriophages present numerous benefits,
timing. The assistance of Holin proteins is necessary for such as high specificity, adaptability, short development cycle,
cell wall lyases to cleave the bacterial cell wall, as the lyases low cost, diversity, abundance, lack of cross-resistance, and
lack signal peptides. Hurst-Hess et al. demonstrated the customization. These advantages position bacteriophages as
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efficient and prompt bactericidal activity of LysB, a protein a promising alternative therapy, particularly in the context
encoded by Mycobacteriophage, against M. abscessus. of the escalating issue of antibiotic resistance. Phage therapy
Subsequently, they conducted in vivo experiments using introduces a novel treatment option for patients who do not
mice to assess the efficacy of LysB against M. abscessus, respond to conventional antibiotic therapy or who display
high levels of resistance to it. Bacteriophages are generally
regarded as safe for human use and have been employed in
certain clinical scenarios (Figure 3). In recent years, there have
been numerous successful instances of mycobacteriophages
being utilized in the treatment of mycobacterial infections,
including those caused by M. abscessus, Mycobacteroides
chelonae, and M. tuberculosis.

6.1. Clinical application of bacteriophage of
M. abscess
Mycobacteria, which are classified as Gram-positive
bacteria, have the potential to induce a range of illnesses,
such as TB, osteomyelitis, arthritis, and soft-tissue
Figure 2. Approaches to phage therapy delivery. Holins and spanins
are represented as components of the lytic life cycle, without current infections. M. abscessus is a rapidly proliferating non-
therapeutic applications tuberculous Mycobacterium that is prevalent in various

Volume 3 Issue 3 (2024) 6 doi: 10.36922/gpd.2935