Efficacy of phage therapy in preclinical models of bacterial infection: a systematic review and meta-analysis

Gómez‐Ochoa, Sergio Alejandro; Pitton, Melissa; Valente, Luca; Vesga, Cristian David Sosa; Largo, Jorge; Quiroga-Centeno, Andrea Carolina; Vargas, Juliana Alexandra Hernández; Trujillo-Cáceres, Silvia Juliana; Muka, Taulant; Cameron, David R.; Que, Yok-Ai

doi:10.1016/s2666-5247(22)00288-9

Cited by 16 publications

(9 citation statements)

References 78 publications

(90 reference statements)

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“…This includes systems for quantifying phage suppression and resistance and a robust in vitro/in vivo model for evaluating cocktail activity against polymicrobial infections. While several of these elements have antecedents in the literature 22,56,57 , their incorporation into an integrated system, will facilitate further development of phage-antibiotic cocktails for these and other pathogens.…”

Section: Discussionmentioning

confidence: 99%

A Blueprint for Broadly Effective Bacteriophage Therapy Against Bacterial Infections

Kim,

Chen,

Echterhof

et al. 2024

Preprint

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Bacteriophage therapy is a tantalizing therapeutic option for anti-microbial resistant bacterial infections but is currently limited to personalized therapy due to the narrow host range of individual phages. Theoretically, cocktails incorporating numerous phages targeting all possible bacterial receptor specificities could confer broad host range. Practically, however, extensive bacterial diversity and the complexity of phage-phage interactions precludes this approach. Here, using screening protocols for identifying 'complementarity groups' of phages using non-redundant receptors, we generate effective, broad-range phage cocktails that prevent emergence of bacterial resistance. Further, phage complementarity groups have characteristic interactions with particular antibiotic classes, making it possible to predict phage-antibiotic as well as phage-phage interactions. Using this strategy, we generate three phage-antibiotic cocktails, each effective against >96% of 153 Pseudomonas aeruginosa clinical isolates, including when used in biofilm cultures and wound infections in vivo. We similarly develop effective Staphylococcus aureus phage-antibiotic cocktails and demonstrate the utility of combined cocktails against polymicrobial (mixed P. aeruginosa/S. aureus) cultures, highlighting the broad applicability of this approach. These studies establish a blueprint for effective, broad-spectrum phage therapy cocktails and enable off-the-shelf phage-based therapeutics for antimicrobial-resistant bacterial infections.

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Section: Discussionmentioning

confidence: 99%

A Blueprint for Broadly Effective Bacteriophage Therapy Against Bacterial Infections

Kim,

Chen,

Echterhof

et al. 2024

Preprint

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“… 17 Meanwhile, Gómez-Ochoa et al employed a broader approach where they searched for animal-only studies published in any language, but their date range was limited to database inception, which was 1963. 84 …”

Section: Discussionmentioning

confidence: 99%

Phage Therapy in the Management of Urinary Tract Infections: A Comprehensive Systematic Review

Al-Anany,

Hooey,

Cook

et al. 2023

PHAGE

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Urinary tract infections (UTIs) are a problem worldwide, affecting almost half a billion people each year. Increasing antibiotic resistance and limited therapeutic options have led to the exploration of alternative therapies for UTIs, including bacteriophage (phage) therapy. This systematic review aims at evaluating the efficacy of phage therapy in treating UTIs. We employed a comprehensive search strategy for any language, any animal, and any publication date. A total of 55 in vivo and clinical studies were included. Of the studies, 22% were published in a non-English language, 32.7% were before the year 1996, and the rest were after 2005. The results of this review suggest that phage therapy for UTIs can be effective; more than 72% of the included articles reported microbiological and clinical improvements. On the other hand, only 5 randomized controlled trials have been completed, and case reports and case series information were frequently incomplete for analysis. Overall, this comprehensive systematic review identifies preliminary evidence supporting the potential of phage therapy as a safe and viable option for the treatment of UTIs.

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“…E. coli is the leading cause of mortality associated with antimicrobial resistance, accounting for over 800,000 lives globally in 2019 alone (59). Several recent studies have proposed phage therapy as a potential alternative to antibiotics against MDR E. coli infections (60). However, it is well-established that intricate surface encapsulation changes can affect phage binding to initiate an attack (10-14, 61, 62).…”

Section: Discussionmentioning

confidence: 99%

Extensive diversity inEscherichia coliGroup 3 capsules is driven by recombination and plasmid transfer from multiple species

Hong

Qin

Forga

et al. 2023

Preprint

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Bacterial capsules provide protection against environmental challenges and host immunity. Historically, Escherichia coli K serotyping scheme, which relies on the hypervariable capsules, has identified around 80 K forms that fall into four distinct groups. Based on recent work by us and others, we predicted that E. coli capsular diversity is grossly underestimated. We exploited Group 3 capsule gene clusters, the best genetically defined capsule group in E. coli, to analyse publicly available E. coli sequences for overlooked capsular diversity within the species. We report the discovery of seven novel Group 3 clusters that fall into two distinct subgroups (3A and 3B). The majority of the 3B capsule clusters were found on plasmids, contrary to the defining feature of Group 3 capsule genes localising at the serA locus on the E. coli chromosome. Other new Group 3 capsule clusters were derived from ancestral sequences through recombination events between shared genes within the serotype variable central region 2. Intriguingly, flanking regions 1 and 3, known to be conserved areas among capsule clusters, showed considerable intra-subgroup variation in clusters from the 3B subgroup, containing genes of shared ancestry with other Enterobacteriaceae species. Variation of Group 3 kps clusters within dominant E. coli lineages, including multi-drug-resistant pathogenic lineages, further supports that E. coli capsules are undergoing rigorous change. Given the pivotal role of capsular polysaccharides in phage predation, our findings raise attention to the need of monitoring kps evolutionary dynamics in pathogenic E. coli in supporting phage therapy.

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Efficacy of phage therapy in preclinical models of bacterial infection: a systematic review and meta-analysis

Cited by 16 publications

References 78 publications

A Blueprint for Broadly Effective Bacteriophage Therapy Against Bacterial Infections

A Blueprint for Broadly Effective Bacteriophage Therapy Against Bacterial Infections

Phage Therapy in the Management of Urinary Tract Infections: A Comprehensive Systematic Review

Extensive diversity inEscherichia coliGroup 3 capsules is driven by recombination and plasmid transfer from multiple species

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