Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis

Allué-Guardia, Anna; Saranathan, Rajagopalan; Chan, John; Torrelles, Jordi B.

doi:10.3390/ijms22020735

Cited by 28 publications

(49 citation statements)

References 237 publications

(308 reference statements)

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“…, Jacobs et al 1993 ; Piuri et al 2009 ). Moreover, they hold great promise for the treatment of drug-resistant tuberculosis strains via bacteriophage therapy, as well as prophylaxis aiding in the prevention of M. tuberculosis infections (see review by Allué-Guardia et al 2021 and references therein). Although studies remain limited to date ( Sula et al 1981 ; Peng et al 2009 ; and see review by Azimi et al 2019 ), research into these medical and therapeutic applications will likely accelerate in the near future, spearheaded by the recently FDA-approved Center for Innovative Phage Applications and Therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Phylogenetic relationships and codon usage bias amongst cluster K mycobacteriophages

Crane

Versoza

Hua

et al. 2021

G3 Genes|Genomes|Genetics

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Bacteriophages infecting pathogenic hosts play an important role in medical research, not only as potential treatments for antibiotic-resistant infections, but also offering novel insights into pathogen genetics and evolution. A prominent example are cluster K mycobacteriophages infecting Mycobacterium tuberculosis, a causative agent of tuberculosis in humans. However, as handling M. tuberculosis as well as other pathogens in a laboratory remains challenging, alternative non-pathogenic relatives, such as M. smegmatis, are frequently used as surrogates to discover therapeutically relevant bacteriophages in a safer environment. Consequently, the individual host ranges of the majority of cluster K mycobacteriophages identified to date remain poorly understood. Here, we characterized the complete genome of Stinson, a temperate sub-cluster K1 mycobacteriophage with a siphoviral morphology. A series of comparative genomic analyses revealed strong similarities with other cluster K mycobacteriophages, including the conservation of an immunity repressor gene and a toxin/antitoxin gene pair. Patterns of codon usage bias across the cluster offered important insights into putative host-ranges in nature, highlighting that although all cluster K mycobacteriophages are able to infect M. tuberculosis, they are less likely to have shared an evolutionary infection history with M. leprae (underlying leprosy) compared to the rest of the genus’ host species. Moreover, sub-cluster K1 mycobacteriophages are able to integrate into the genomes of M. abscessus and M. marinum—two bacteria causing pulmonary and cutaneous infections which are often difficult to treat due to their drug resistance.

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Section: Introductionmentioning

confidence: 99%

Phylogenetic relationships and codon usage bias amongst cluster K mycobacteriophages

Crane

Versoza

Hua

et al. 2021

G3 Genes|Genomes|Genetics

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“…Resistance would thus arise no faster than to antibiotics and only against a single phage at a time. By targeting a range of highly conserved surface receptors that are essential for bacterial survival, and by constantly monitoring resistance arising and updating the phage cocktail, such treatments should remain effective for a long time [10]. Importantly, evolution of broad anti-bacteriophage mechanisms, as seen in response to conventional antibiotic therapy, are unlikely to arise because drug-resistant M. tuberculosis strains accumulate individual target gene mutations rather than broad defence mechanisms such as efflux pumps.…”

Section: Mycobacteriophage Treatmentmentioning

confidence: 99%

“…In the USA, the use of phages is approved for the decontamination of food, plant-based and livestock products, or surfaces [10]. In this context, the U.S. Environmental Protection Agency (EPA) has stated that the literature demonstrates that bacteriophages are ubiquitous naturally occurring organisms, that humans are exposed daily to these organisms without adverse effects, and that phages are non-toxic and non-pathogenic to humans and animals [75].…”

Section: Mycobacteriophage Treatmentmentioning

confidence: 99%

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Mycobacteriophages to Treat Tuberculosis: Dream or Delusion?

et al. 2021

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Rates of antimicrobial resistance are increasing globally while the pipeline of new antibiotics is drying up, putting patients with disease caused by drug-resistant bacteria at increased risk of complications and death. The growing costs for diagnosis and management of drug resistance threaten tuberculosis control where the disease is endemic and resources limited. Bacteriophages are viruses that attack bacteria. Phage preparations served as anti-infective agents long before antibiotics were discovered. Though small in size, phages are the most abundant and diverse biological entity on earth. Phages have co-evolved with their hosts and possess all the tools needed to infect and kill bacteria, independent of drug resistance. Modern biotechnology has improved our understanding of the biology of phages and their possible uses. Phage preparations are available to treat meat, fruit, vegetables, and dairy products against parasites or to prevent contamination with human pathogens, such as Listeria monocytogenes, Escherichia coli, or Staphylococcus aureus. Such phage-treated products are considered fit for human consumption. A number of recent case reports describe in great detail the successful treatment of highly drug-resistant infections with individualized phage preparations. Formal clinical trials with standardized products are slowly emerging. With its highly conserved genome and relative paucity of natural phage defence mechanisms Mycobacterium tuberculosis appears to be a suitable target for phage treatment. A phage cocktail with diverse and strictly lytic phages that kill all lineages of M. tuberculosis, and can be propagated on Mycobacterium smegmatis, has been assembled and is available for the evaluation of optimal dosage and suitable routes of administration for tuberculosis in humans. Phage treatment can be expected to be safe and active on extracellular organisms, but phage penetration to intracellular and granulomatous environments as well as synergistic effects with antibiotics are important questions to address during further evaluation.

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“…An estimated half million infections were rifampin-resistant tuberculosis, and 206,030 were multidrug-resistant tuberculosis (MDR-TB), a 10% increase from 2018 ( 1 ). Characterized bacteriophages could offer an alternative treatment option for MDR-TB ( 2 , 3 ). Mycobacteriophage Joy99 was discovered in soil from a municipal mulch pile in Saint Louis, MO (global positioning system [GPS] coordinates 38.664567 N, 90.3179 W) ( 4 , 5 ).…”

Section: Announcementmentioning

confidence: 99%