Directed Evolution of a Mycobacteriophage

Cebriá-Mendoza, María; Sanjuán, Rafael; Domingo‐Calap, Pilar

doi:10.3390/antibiotics8020046

Cited by 10 publications

(8 citation statements)

References 30 publications

(36 reference statements)

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“…The study investigated the effect of phage inoculum size to achieve desired adaption. 155 Interestingly, their data suggest that using a smaller phage inoculum during evolution studies helps to achieve higher titer, greater plaque size, and efficient lysis compared to larger regimes. As some mycobacteriophage can infect both M. smegmatis and M. tuberculosis, the same study could be expanded using M. tuberculosis as a host for enhancing the potential of phage as a therapeutic.…”

Section: Directed Evolution To Improve Phage Therapymentioning

confidence: 99%

“…As some mycobacteriophage can infect both M. smegmatis and M. tuberculosis, the same study could be expanded using M. tuberculosis as a host for enhancing the potential of phage as a therapeutic. 155 In another study, directed evolution was used for limiting the host range of T7 bacteriophages. T7 phage was grown in the presence of five restrictive and one permissive strain for propagation.…”

Section: Directed Evolution To Improve Phage Therapymentioning

confidence: 99%

See 1 more Smart Citation

Phage engineering and phage‐assisted CRISPR‐Cas delivery to combat multidrug‐resistant pathogens

Khambhati

Bhattacharjee

Gohil

et al. 2022

Bioengineering & Transla Med

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Antibiotic resistance ranks among the top threats to humanity. Due to the frequent use of antibiotics, society is facing a high prevalence of multidrug resistant pathogens, which have managed to evolve mechanisms that help them evade the last line of therapeutics. An alternative to antibiotics could involve the use of bacteriophages (phages), which are the natural predators of bacterial cells. In earlier times, phages were implemented as therapeutic agents for a century but were mainly replaced with antibiotics, and considering the menace of antimicrobial resistance, it might again become of interest due to the increasing threat of antibiotic resistance among pathogens. The current understanding of phage biology and clustered regularly interspaced short palindromic repeats (CRISPR) assisted phage genome engineering techniques have facilitated to generate phage variants with unique therapeutic values. In this review, we briefly explain strategies to engineer bacteriophages. Next, we highlight the literature supporting CRISPR-Cas9-assisted phage engineering for effective and more specific targeting of bacterial pathogens. Lastly, we discuss techniques that either help to increase the fitness, specificity, or lytic ability of bacteriophages to control an infection.

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Section: Directed Evolution To Improve Phage Therapymentioning

confidence: 99%

Section: Directed Evolution To Improve Phage Therapymentioning

confidence: 99%

Phage engineering and phage‐assisted CRISPR‐Cas delivery to combat multidrug‐resistant pathogens

Khambhati

Bhattacharjee

Gohil

et al. 2022

Bioengineering & Transla Med

View full text Add to dashboard Cite

show abstract

“…Such is the case of cluster G phage mutants with single residue substitutions in their tail proteins that infect M. tuberculosis strains more efficiently [ 156 ]. The use of directed evolution is also being explored as a tool to increase the infectivity of mycobacteriophages under different experimental conditions [ 160 ].…”

Section: Phage Therapy To Treat Multidrug-resistant Tbmentioning

confidence: 99%

Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis

Allué-Guardia

Saranathan

Chan

et al. 2021

IJMS

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The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage therapy against bacteria has been around for more than a century and, although its implementation was abandoned after the introduction of drugs, it is now making a comeback and gaining renewed interest in Western medicine as an alternative to treat drug-resistant pathogens. Mycobacteriophages are genetically diverse viruses that specifically infect mycobacterial hosts, including members of the M. tuberculosis complex. This review describes general features of mycobacteriophages and their mechanisms of killing M. tuberculosis, as well as their advantages and limitations as therapeutic and prophylactic agents against drug-resistant M. tuberculosis strains. This review also discusses the role of human lung micro-environments in shaping the availability of mycobacteriophage receptors on the M. tuberculosis cell envelope surface, the risk of potential development of bacterial resistance to mycobacteriophages, and the interactions with the mammalian host immune system. Finally, it summarizes the knowledge gaps and defines key questions to be addressed regarding the clinical application of phage therapy for the treatment of drug-resistant tuberculosis.

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“…This is because they only replicate in the presence of bacteria causing the infection, thus reducing damage to the natural microflora. In addition, genetic exchange between phages rarely happens [16][17][18]. Therefore, as the frequency of therapy increases, the treatment doses and periods needed to achieve an optimal effect are expected to decrease [16,17].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, genetic exchange between phages rarely happens [16][17][18]. Therefore, as the frequency of therapy increases, the treatment doses and periods needed to achieve an optimal effect are expected to decrease [16,17]. Phage therapy has been used for the treatment of infections related to burn injuries or soft tissue and skin trauma, osteomyelitis, sepsis, bacteremia, and otitis media as well as urinary tract, pulmonary, and prosthetic device-associated infections.…”

Section: Introductionmentioning

confidence: 99%

Phage Therapy in the Era of Multidrug Resistance in Bacteria: A Systematic Review

Aranaga

Pantoja

Martínez

et al. 2022

IJMS

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Bacteriophages offer an alternative for the treatment of multidrug-resistant bacterial diseases as their mechanism of action differs from that of antibiotics. However, their application in the clinical field is limited to specific cases of patients with few or no other alternative therapies. This systematic review assesses the effectiveness and safety of phage therapy against multidrug-resistant bacteria through the evaluation of studies published over the past decade. To that end, a bibliographic search was carried out in the PubMed, Science Direct, and Google Scholar databases. Of the 1500 studies found, 27 met the inclusion criteria, with a total of 165 treated patients. Treatment effectiveness, defined as the reduction in or elimination of the bacterial load, was 85%. Except for two patients who died from causes unrelated to phage therapy, no serious adverse events were reported. This shows that phage therapy could be an alternative treatment for patients with infections associated with multidrug-resistant bacteria. However, owing to the phage specificity required for the treatment of various bacterial strains, this therapy must be personalized in terms of bacteriophage type, route of administration, and dosage.

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Directed Evolution of a Mycobacteriophage

Cited by 10 publications

References 30 publications

Phage engineering and phage‐assisted CRISPR‐Cas delivery to combat multidrug‐resistant pathogens

Phage engineering and phage‐assisted CRISPR‐Cas delivery to combat multidrug‐resistant pathogens

Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis

Phage Therapy in the Era of Multidrug Resistance in Bacteria: A Systematic Review

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