Bacteriophages-Based Technologies for a One Health Society: Applications in Clinical, Veterinary, and Industrial Settings

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 19403

Special Issue Editors

School of Chemistry & Molecular Biosciences, Australian Centre for Ecogenomics, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia
Interests: bacteriophage; antibiotic resistance; synthetic biology; biofilms
Director of Research and Development for TAILΦR Service Center, Baylor College of Medicine, Houston, TX 77030, USA
Interests: bacteriophages; microbiome; phage therapy; antibiotic resistance; E. coli

Special Issue Information

Dear Colleagues,

An alarming escalating rise in global multi-drug resistant bacteria presents a huge environmental, social and economic burden. Suitable alternatives to traditional antibiotic treatments are now being sought in a range of settings. Bacteriophages (phages for short) are viruses that target, infect and kill bacteria. Phage therapy has been a much under-explored alternative to antibiotic use, but a renaissance in phage-based therapies is now highly anticipated.

This Microorganisms research topic will offer deep insights into the latest developments of research dedicated to bacteriophage therapy, consistent with a ‘One Health’ approach, providing potential alternative solutions to treating bacterial pathogens with phages.

This Special Issue topic will appeal to, and provide a platform for, researchers interested in the potential for phage therapy to share their recent results in a variety of environments, including clinical settings, veterinary medicine, and industrial applications, such as food and beverage industries. Research relating to phage therapy in farming practices, namely agriculture and aquaculture, is also very much welcomed. These findings will provide a foundation to enlarge the current application of phage therapies in the treatment of recalcitrant pathogenic bacteria.

We look forward to assembling an issue that highlights some of the best current research in applications for phage therapy across diverse environments.

Dr. Karen D. Weynberg
Dr. Sabrina Green
Guest Editors

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Keywords

  • antibiotic resistance
  • bacteriophage therapy
  • One Health

Published Papers (5 papers)

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Research

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12 pages, 2744 KiB  
Article
Exploration of Bacterial Re-Growth as In Vitro Phenomenon Affecting Methods for Analysis of the Antimicrobial Activity of Chimeric Bacteriophage Endolysins
by Ursula Kaspar, Nina Schleimer, Evgeny A. Idelevich, Sonja Molinaro and Karsten Becker
Microorganisms 2022, 10(2), 445; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10020445 - 15 Feb 2022
Cited by 4 | Viewed by 2095
Abstract
Drug alternatives to combat methicillin-resistant Staphylococcus aureus (MRSA) in human and animal healthcare are urgently needed. Recently, the recombinant bacteriophage endolysins, PRF-119 and its successor substance HY-133, have proven to be highly active against various S. aureus clonal lineages and to exhibit a [...] Read more.
Drug alternatives to combat methicillin-resistant Staphylococcus aureus (MRSA) in human and animal healthcare are urgently needed. Recently, the recombinant bacteriophage endolysins, PRF-119 and its successor substance HY-133, have proven to be highly active against various S. aureus clonal lineages and to exhibit a very rapid bactericidal effect when standard methods for susceptibility testing are applied. Along with subsequent growth curve experiments, a re-growth phenomenon was observed in vitro necessitating its clarification for the assessment of the agent’s stability and activity as well as for methodological aspects of endolysin testing in general. Distinct in vitro parameters were comparatively examined applying also scanning electron microscopy, fluorescence assays and SDS-PAGE analysis. The shape and material of the culture vessels as well as the shaking conditions were identified as factors influencing the in vitro stability and activity of HY-133. The highest function maintenance was observed in plain centrifuge tubes. Based on this, the conditions and parameters of assays for testing the antimicrobial activities of phage endolysins were determined and adjusted. In particular, shear forces should be kept to a minimum. Our results form the basis for both future test standardization and re-growth-independent experiments as prerequisites for exact determination of the antimicrobial activities of engineered endolysins. Full article
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20 pages, 4955 KiB  
Article
Novel Bacteriophages Show Activity against Selected Australian Clinical Strains of Pseudomonas aeruginosa
by Samuel Namonyo, Gilda Carvalho, Jianhua Guo and Karen D. Weynberg
Microorganisms 2022, 10(2), 210; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10020210 - 19 Jan 2022
Cited by 6 | Viewed by 2005
Abstract
Multi-drug resistant (MDR) clinical strains of Pseudomonas aeruginosa are the most prevalent bacteria in the lungs of patients with cystic fibrosis (CF) and burn wounds and among the most common in immunocompromised hospital patients in Australia. There are currently no promising antibiotics in [...] Read more.
Multi-drug resistant (MDR) clinical strains of Pseudomonas aeruginosa are the most prevalent bacteria in the lungs of patients with cystic fibrosis (CF) and burn wounds and among the most common in immunocompromised hospital patients in Australia. There are currently no promising antibiotics in the pipeline being developed against these strains. Phage therapy, which uses viruses known as bacteriophages to infect and kill pathogenic bacteria, could be a possible alternative treatment. To this end, we isolated and characterised four novel phages against Australian clinical strains of P. aeruginosa isolated from patients with cystic fibrosis, from infected blood and joint aspirate in Southeast Queensland, Australia. Activated sludge was enriched for phages using the clinical strains, and four bacteriophages were isolated. The phages were able to cause lysis in a further three identified clinical isolates. Morphology showed that they were all tailed phages (of the order Caudovirales), two belonging to the family Myoviridae and the others assigned to the Podoviridae and Siphoviridae. Their genomes were sequenced to reveal a doubled stranded DNA topology with genome sizes ranging from 42 kb to 65 kb. In isolating and characterising these novel phages, we directed our efforts toward the development and use of these phages as candidates for phage therapy as an alternative strategy for the management or elimination of these pathogenic strains. Here we describe novel phage candidates for potential therapeutic treatment of MDR Australian clinical isolates of P. aeruginosa. Full article
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21 pages, 4291 KiB  
Article
A Mycobacteriophage-Based Vaccine Platform: SARS-CoV-2 Antigen Expression and Display
by Krista G. Freeman, Katherine S. Wetzel, Yu Zhang, Kira M. Zack, Deborah Jacobs-Sera, Sara M. Walters, Dominique J. Barbeau, Anita K. McElroy, John V. Williams and Graham F. Hatfull
Microorganisms 2021, 9(12), 2414; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9122414 - 23 Nov 2021
Cited by 6 | Viewed by 2417
Abstract
The explosion of SARS-CoV-2 infections in 2020 prompted a flurry of activity in vaccine development and exploration of various vaccine platforms, some well-established and some new. Phage-based vaccines were described previously, and we explored the possibility of using mycobacteriophages as a platform for [...] Read more.
The explosion of SARS-CoV-2 infections in 2020 prompted a flurry of activity in vaccine development and exploration of various vaccine platforms, some well-established and some new. Phage-based vaccines were described previously, and we explored the possibility of using mycobacteriophages as a platform for displaying antigens of SARS-CoV-2 or other infectious agents. The potential advantages of using mycobacteriophages are that a large and diverse variety of them have been described and genomically characterized, engineering tools are available, and there is the capacity to display up to 700 antigen copies on a single particle approximately 100 nm in size. The phage body may itself be a good adjuvant, and the phages can be propagated easily, cheaply, and to high purity. Furthermore, the recent use of these phages therapeutically, including by intravenous administration, suggests an excellent safety profile, although efficacy can be restricted by neutralizing antibodies. We describe here the potent immunogenicity of mycobacteriophage Bxb1, and Bxb1 recombinants displaying SARS-CoV-2 Spike protein antigens. Full article
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20 pages, 2950 KiB  
Article
Novel Phage-Derived Depolymerase with Activity against Proteus mirabilis Biofilms
by Cormac J. Rice, Stephen A. Kelly, Seamus C. O’Brien, Erinn M. Melaugh, Jan C. B. Ganacias, Zheng Hua Chai, Brendan F. Gilmore and Timofey Skvortsov
Microorganisms 2021, 9(10), 2172; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9102172 - 19 Oct 2021
Cited by 14 | Viewed by 5199
Abstract
The adherence of Proteus mirabilis to the surface of urinary catheters leads to colonization and eventual blockage of the catheter lumen by unique crystalline biofilms produced by these opportunistic pathogens, making P. mirabilis one of the leading causes of catheter-associated urinary tract infections. [...] Read more.
The adherence of Proteus mirabilis to the surface of urinary catheters leads to colonization and eventual blockage of the catheter lumen by unique crystalline biofilms produced by these opportunistic pathogens, making P. mirabilis one of the leading causes of catheter-associated urinary tract infections. The Proteus biofilms reduce efficiency of antibiotic-based treatment, which in turn increases the risk of antibiotic resistance development. Bacteriophages and their enzymes have recently become investigated as alternative treatment options. In this study, a novel Proteus bacteriophage (vB_PmiS_PM-CJR) was isolated from an environmental sample and fully characterized. The phage displayed depolymerase activity and the subsequent genome analysis revealed the presence of a pectate lyase domain in its tail spike protein. The protein was heterologously expressed and purified; the ability of the purified tail spike to degrade Proteus biofilms was tested. We showed that the application of the tail spike protein was able to reduce the adherence of bacterial biofilm to plastic pegs in a MBEC (minimum biofilm eradication concentration) assay and improve the survival of Galleria mellonella larvae infected with Proteus mirabilis. Our study is the first to successfully isolate and characterize a biofilm depolymerase from a Proteus phage, demonstrating the potential of this group of enzymes in treatment of Proteus infections. Full article
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Review

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20 pages, 613 KiB  
Review
Essential Topics for the Regulatory Consideration of Phages as Clinically Valuable Therapeutic Agents: A Perspective from Spain
by Roberto Vázquez, Roberto Díez-Martínez, Pilar Domingo-Calap, Pedro García, Diana Gutiérrez, Maite Muniesa, María Ruiz-Ruigómez, Rafael Sanjuán, María Tomás, María Ángeles Tormo-Mas and Pilar García
Microorganisms 2022, 10(4), 717; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10040717 - 26 Mar 2022
Cited by 12 | Viewed by 6174
Abstract
Antibiotic resistance is one of the major challenges that humankind shall face in the short term. (Bacterio)phage therapy is a valuable therapeutic alternative to antibiotics and, although the concept is almost as old as the discovery of phages, its wide application was hindered [...] Read more.
Antibiotic resistance is one of the major challenges that humankind shall face in the short term. (Bacterio)phage therapy is a valuable therapeutic alternative to antibiotics and, although the concept is almost as old as the discovery of phages, its wide application was hindered in the West by the discovery and development of antibiotics in the mid-twentieth century. However, research on phage therapy is currently experiencing a renaissance due to the antimicrobial resistance problem. Some countries are already adopting new ad hoc regulations to favor the short-term implantation of phage therapy in clinical practice. In this regard, the Phage Therapy Work Group from FAGOMA (Spanish Network of Bacteriophages and Transducing Elements) recently contacted the Spanish Drugs and Medical Devices Agency (AEMPS) to promote the regulation of phage therapy in Spain. As a result, FAGOMA was asked to provide a general view on key issues regarding phage therapy legislation. This review comes as the culmination of the FAGOMA initiative and aims at appropriately informing the regulatory debate on phage therapy. Full article
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