The Phage: Biology and Therapeutic Use

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 16666

Special Issue Editors


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Guest Editor
School of Life Sciences, University of Nottingham, Nottingham, UK
Interests: phage therapy

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Guest Editor
Evolution Biotechnologies, Sharnbrook, UK
Interests: phage therapy; biological control

Special Issue Information

Dear Colleagues,

Phage therapy -  the use of bacteriophages as specific antibacterial therapeutic agents – has been around for over a hundred years. In that time it has been seen as everything from an almost miraculous cure to a failed alternative to “real” medicine. In recent years, based on a far more complete understanding of bacteriophage biology, opinion has swung once again and bacteriophages are seen once more as a viable approach to the very real crisis of antibiotic resistance. As it has been for some time, the key is obtaining hard, verifiable clinical data.

This special edition of “Microorganisms”, entitled "The Phage: Biology and Therapeutic Use" is intended to contain both reviews and original articles focussed on the emerging data in the field, and on supporting the viability of this approach in an area with real unmet need. With invited articles contributed by experts from around the world, it is intended to form a valuable resource for both workers in the field and curious newcomers to the sometimes abstruse field of bacteriophages, their biology, and the emerging potential for their therapeutic use.

Prof. Dr. Richard James
Dr. David R. Harper
Guest Editors

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Keywords

  • bacteriophage
  • phage therapy
  • antibiotic resistance
  • novel antibiotics
  • clinical trials

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Published Papers (4 papers)

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Research

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24 pages, 11828 KiB  
Article
The Citizen Phage Library: Rapid Isolation of Phages for the Treatment of Antibiotic Resistant Infections in the UK
by Julie Fletcher, Robyn Manley, Christian Fitch, Christina Bugert, Karen Moore, Audrey Farbos, Michelle Michelsen, Shayma Alathari, Nicola Senior, Alice Mills, Natalie Whitehead, James Soothill, Stephen Michell and Ben Temperton
Microorganisms 2024, 12(2), 253; https://doi.org/10.3390/microorganisms12020253 - 25 Jan 2024
Cited by 3 | Viewed by 5508
Abstract
Antimicrobial resistance poses one of the greatest threats to global health and there is an urgent need for new therapeutic options. Phages are viruses that infect and kill bacteria and phage therapy could provide a valuable tool for the treatment of multidrug-resistant infections. [...] Read more.
Antimicrobial resistance poses one of the greatest threats to global health and there is an urgent need for new therapeutic options. Phages are viruses that infect and kill bacteria and phage therapy could provide a valuable tool for the treatment of multidrug-resistant infections. In this study, water samples collected by citizen scientists as part of the Citizen Phage Library (CPL) project, and wastewater samples from the Environment Agency yielded phages with activity against clinical strains Klebsiella pneumoniae BPRG1484 and Enterobacter cloacae BPRG1482. A total of 169 and 163 phages were found for K. pneumoniae and E. cloacae, respectively, within four days of receiving the strains. A third strain (Escherichia coli BPRG1486) demonstrated cross-reactivity with 42 E. coli phages already held in the CPL collection. Seed lots were prepared for four K. pneumoniae phages and a cocktail combining these phages was found to reduce melanisation in a Galleria mellonella infection model. The resources and protocols utilised by the Citizen Phage Library enabled the rapid isolation and characterisation of phages targeted against multiple strains. In the future, within a clearly defined regulatory framework, phage therapy could be made available on a named-patient basis within the UK. Full article
(This article belongs to the Special Issue The Phage: Biology and Therapeutic Use)
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15 pages, 2135 KiB  
Article
Efficacy of Different Encapsulation Techniques on the Viability and Stability of Diverse Phage under Simulated Gastric Conditions
by Sicelo B. Dlamini, Adriano M. Gigante, Steven P. T. Hooton and Robert J. Atterbury
Microorganisms 2023, 11(10), 2389; https://doi.org/10.3390/microorganisms11102389 - 25 Sep 2023
Cited by 2 | Viewed by 2268
Abstract
Salmonella causes a range of diseases in humans and livestock of considerable public health and economic importance. Widespread antimicrobial use, particularly in intensively produced livestock (e.g., poultry and pigs) may contribute to the rise of multidrug-resistant Salmonella strains. Alternative treatments such as bacteriophages [...] Read more.
Salmonella causes a range of diseases in humans and livestock of considerable public health and economic importance. Widespread antimicrobial use, particularly in intensively produced livestock (e.g., poultry and pigs) may contribute to the rise of multidrug-resistant Salmonella strains. Alternative treatments such as bacteriophages have shown promise when used to reduce the intestinal carriage of Salmonella in livestock. However, the digestive enzymes and low pH encountered in the monogastric GI tract can significantly reduce phage viability and impact therapeutic outcomes. This study deployed alginate–carrageenan microcapsules with and without CaCO3 to protect a genomically diverse set of five Salmonella bacteriophages from simulated gastrointestinal conditions. None of the unprotected phage could be recovered following exposure to pH < 3 for 10 min. Alginate–carrageenan encapsulation improved phage viability at pH 2–2.5 after exposure for 10 min, but not at pH 2 after 1 h. Including 1% (w/v) CaCO3 in the formulation further reduced phage loss to <0.5 log10 PFU/mL, even after 1 h at pH 2. In all cases, phage were efficiently released from the microcapsules following a shift to a neutral pH (7.5), simulating passage to the duodenum. In summary, alginate–carrageenan-CaCO3 encapsulation is a promising approach for targeted intestinal delivery of genomically diverse Salmonella bacteriophages. Full article
(This article belongs to the Special Issue The Phage: Biology and Therapeutic Use)
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8 pages, 1831 KiB  
Communication
Peptidoglycan Endopeptidase from Novel Adaiavirus Bacteriophage Lyses Pseudomonas aeruginosa Strains as Well as Arthrobacter globiformis and A. pascens Bacteria
by Karel Petrzik
Microorganisms 2023, 11(8), 1888; https://doi.org/10.3390/microorganisms11081888 - 26 Jul 2023
Viewed by 1152
Abstract
A novel virus lytic for Pseudomonas aeruginosa has been purified. Its viral particles have a siphoviral morphology with a head 60 nm in diameter and a noncontractile tail 184 nm long. The dsDNA genome consists of 16,449 bp, has cohesive 3′ termini, and [...] Read more.
A novel virus lytic for Pseudomonas aeruginosa has been purified. Its viral particles have a siphoviral morphology with a head 60 nm in diameter and a noncontractile tail 184 nm long. The dsDNA genome consists of 16,449 bp, has cohesive 3′ termini, and encodes 28 putative proteins in a single strain. The peptidoglycan endopeptidase encoded by ORF 16 was found to be the lytic enzyme of this virus. The recombinant, purified enzyme was active up to 55 °C in the pH range 6–9 against all tested isolates of P. aeruginosa, but, surprisingly, also against the distant Gram-positive micrococci Arthrobacter globiformis and A. pascens. Both this virus and its endolysin are further candidates for possible treatment against P. aeruginosa and probably also other bacteria. Full article
(This article belongs to the Special Issue The Phage: Biology and Therapeutic Use)
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Review

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20 pages, 415 KiB  
Review
The Biotechnological Application of Bacteriophages: What to Do and Where to Go in the Middle of the Post-Antibiotic Era
by Su Jin Jo, Jun Kwon, Sang Guen Kim and Seung-Jun Lee
Microorganisms 2023, 11(9), 2311; https://doi.org/10.3390/microorganisms11092311 - 13 Sep 2023
Cited by 10 | Viewed by 5131
Abstract
Amid the escalating challenges of antibiotic resistance, bacterial infections have emerged as a global threat. Bacteriophages (phages), viral entities capable of selectively infecting bacteria, are gaining momentum as promising alternatives to traditional antibiotics. Their distinctive attributes, including host specificity, inherent self-amplification, and potential [...] Read more.
Amid the escalating challenges of antibiotic resistance, bacterial infections have emerged as a global threat. Bacteriophages (phages), viral entities capable of selectively infecting bacteria, are gaining momentum as promising alternatives to traditional antibiotics. Their distinctive attributes, including host specificity, inherent self-amplification, and potential synergy with antibiotics, render them compelling candidates. Phage engineering, a burgeoning discipline, involves the strategic modification of bacteriophages to enhance their therapeutic potential and broaden their applications. The integration of CRISPR-Cas systems facilitates precise genetic modifications, enabling phages to serve as carriers of functional genes/proteins, thereby enhancing diagnostics, drug delivery, and therapy. Phage engineering holds promise in transforming precision medicine, addressing antibiotic resistance, and advancing diverse applications. Emphasizing the profound therapeutic potential of phages, this review underscores their pivotal role in combatting bacterial diseases and highlights their significance in the post-antibiotic era. Full article
(This article belongs to the Special Issue The Phage: Biology and Therapeutic Use)
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