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Gene & Protein in Disease Phage therapy for Mycobacterium infections

6.2. Clinical application of bacteriophage of
M. chelonae
M. chelonae is a rapidly growing, non-tuberculous
Mycobacterium that may cause chronic infections in immune-
compromised hosts. This organism is widely distributed in
the environment and most commonly manifests clinically
as a localized skin or soft-tissue infection or disseminated
skin disease. In the treatment of localized infections, such
as skin infections and osteomyelitis, the utilization of
mycobacteriophages has demonstrated favorable outcomes
and decreased the necessity for prolonged antibiotic therapy.
Mycobacteriophages exhibit a high degree of specificity
Figure 3. The selection and application of the bacteriophages
against M. chelonae, rendering them valuable in the
management of localized infections. Little et al. reported
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environmental settings. M. abscessus infection is a that a 56-year-old patient with refractory M. chelonae
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bacterial infection resulting from the Mycobacterium infection was treated with mycobacteriophage and that the
genus, typically manifesting in proximity to compromised patient’s skin lesions significantly improved.
skin, soft tissue, or bone, and frequently observed in
individuals with weakened immune systems. M. abscessus The advantage of using mycobacteriophage for the
is a clinically common opportunistic pathogen that treatment of localized infections is that it selectively
can infect the bronchial airways of patients with cystic infects and kills M. chelonae without causing damage to
fibrosis, chronic obstructive pulmonary disease, or normal human cells. In addition, phage therapy can also
bronchiectasis, 70,71 and cause disseminated infection in help reduce the use of antibiotics, thereby alleviating
immune-compromised and post-operative patients. It is the problem associated with antibiotic resistance and
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extremely antibiotic-resistant, making it one of the most shortening the treatment period, reducing patient suffering
challenging mycobacterial infections to manage. 73,74 The and healthcare costs.
standard treatment for M. abscessus lung infection involves 6.3. Clinical application of bacteriophage of
prolonged intravenous administration of a combination M. tuberculosis
of macrolides, aminoglycosides, and β-lactam antibiotics.
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However, the success rate of this treatment is only 45%, M. tuberculosis, the causative agent of human TB, has
indicating limited efficacy. The inherent resistance of afflicted humans for approximately 9000 years. The earliest
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M. abscessus to a wide range of antimicrobial agents documented instances of the disease in India and China
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restricts therapeutic options and contributes to unfavorable date back over 3000 years. With the advent of antibiotics
treatment outcomes. The initial effective application of such as streptomycin and isoniazid, the end of TB has been
bacteriophage in treating mycobacterial infection was declared since the late 1950s and early 1960s. 81,82 However,
demonstrated in a 15-year-old patient with cystic fibrosis since the 1990s, there has been a global resurgence of TB
who had contracted disseminated M. abscess following and the emergence of MDR, extensively drug-resistant,
bilateral lung transplantation. A mixture of three phages, and fully drug-resistant M. tuberculosis strains. 83,84 In
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Muddy, ZoeJ, and BPs, was administered intravenously developing nations, the prolonged treatment duration,
in the absence of phage resistance. The phages were adverse side effects, and relatively high cost contribute to
selected based on their ability to infect M. smegmatis and poor adherence to treatment regimens, exacerbating the
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M. abscessus. However, it was found that two of these development of drug-resistant strains and diminishing
mycobacteriophages exhibit low virulence and necessitate the effectiveness of antibiotics.
modification to enhance their antimicrobial efficacy. Mycobacteriophages are viral agents that target
Subsequently, Nick et al. implemented phage therapy in a mycobacteria, including pathogenic M. tuberculosis. These
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cystic fibrosis patient with a lung M. abscess in September phages have been investigated for their potential use in
2020. On day 379 post-phage administration, the patient clinical applications, particularly in the treatment of drug-
underwent a successful lung transplant surgery. This resistant TB. The results of Li et al. demonstrated that
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represents the initial instance of effectively treating drug- phage D29 could alleviate organ lesions and reduce colony-
resistant mycobacterial lung infection using phage therapy, forming units in the organs of guinea pigs afflicted with
offering novel avenues for addressing severe mycobacterial drug-resistant TB. In addition, D29 enhanced the cellular
lung infections and infections in other organs in the future. immune response without inducing adverse effects in the

Volume 3 Issue 3 (2024) 7 doi: 10.36922/gpd.2935