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Special Issue "Hurdles for Phage Therapy (PT) to Become a Reality"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Bacterial Viruses".

Deadline for manuscript submissions: closed (15 February 2019)

Special Issue Editor

Guest Editor
Dr. Harald Brüssow

Nestlé Research Center, Lausanne, Switzerland
E-Mail
Interests: Diarrhea, Bacteriophages, Microbiota, Nutrition and Health, Pediatrics

Special Issue Information

Dear Colleagues,

With the rise of antibiotic resistance to critical levels in a number of important bacterial pathogens, a return to a pre-antibiotic era is feared. Consequently, interest into alternative antimicrobial agents has grown. Phage therapy is a potential alternative or an adjunct to antibiotics. Indeed, commercial phage cocktails against numerous bacterial infections are available as over-the-counter drugs in several member states of the former Soviet Union. However, only few exploratory controlled human phage therapy trials have been conducted outside the Soviet Union and no phage products have so far been registered for medical use in Western countries.

In this Special Issue of Viruses, we want to explore reasons for the lack of clinical progress in the field of phage therapy by conducting a gap analysis. Particularly welcome are critical analyses of our knowledge gaps on phage-pathogen interaction in animal or human hosts, articles that suggest regulatory requirements for such medical phage products, contributions that discuss models to finance phage production and controlled clinical trials, and discussions on the role of governmental and international health agencies in this process. Phage therapy will not be a panacea and we invite manuscripts that identify infectious diseases that are likely to respond to phage therapy.

Specific knowledge gaps:

1)   What in vitro phenotypes of phages could guide the selection of phages with suitable in vivo phenotype for PT?
2)   Is metagenome analysis from natural infection sites in humans a better way to identify phages with suitable in vivo replication potential?
3)   The problem of producing the therapeutically phage on pathogenic vs. non-pathogenic production strains.
4)   Purification, formulation and genetic safety assessment of the produced phages.
5)   Resistance development to phages occurring during PT.
6)   The unchartered area of phage-bacterium interaction within the mammalian or avian host.

Practical aspects:

7)   Is it possible to formulate a set of rules with respect to infection type, which predict successful interventions?
8)   Learning lessons from previous clinical trials.
9)   The regulatory framework for PT.
10) Need PT trials be organized by governmental agencies?
11) NGO and crowd funding for PT in developing countries.

Dr. Harald Brüssow
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Phage therapy
  • phage phenotypes
  • infection targets
  • in vivo phage-bacterium interaction
  • clinical trial organization

Published Papers (30 papers)

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Research

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Open AccessCommunication
New Bacteriophages against Emerging Lineages ST23 and ST258 of Klebsiella pneumoniae and Efficacy Assessment in Galleria mellonella Larvae
Viruses 2019, 11(5), 411; https://doi.org/10.3390/v11050411
Received: 14 February 2019 / Revised: 26 April 2019 / Accepted: 29 April 2019 / Published: 3 May 2019
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Abstract
Klebsiella pneumoniae is a bacterial pathogen of high public health importance. Its polysaccharide capsule is highly variable but only a few capsular types are associated with emerging pathogenic sublineages. The aim of this work is to isolate and characterize new lytic bacteriophages and [...] Read more.
Klebsiella pneumoniae is a bacterial pathogen of high public health importance. Its polysaccharide capsule is highly variable but only a few capsular types are associated with emerging pathogenic sublineages. The aim of this work is to isolate and characterize new lytic bacteriophages and assess their potential to control infections by the ST23 and ST258 K. pneumoniae sublineages using a Galleria mellonella larvae model. Three selected bacteriophages, targeting lineages ST258 (bacteriophages vB_KpnP_KL106-ULIP47 and vB_KpnP_KL106-ULIP54) and ST23 (bacteriophage vB_KpnP_K1-ULIP33), display specificity for capsular types KL106 and K1, respectively. These podoviruses belong to the Autographivirinae subfamily and their genomes are devoid of lysogeny or toxin-associated genes. In a G. mellonella larvae model, a mortality rate of 70% was observed upon infection by K. pneumoniae ST258 and ST23. This number was reduced to 20% upon treatment with bacteriophages at a multiplicity of infection of 10. This work increases the number of characterized bacteriophages infecting K. pneumoniae and provides information regarding genome sequence and efficacy during preclinical phage therapy against two prominent sublineages of this bacterial species. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessArticle
Protection of Phage Applications in Crop Production: A Patent Landscape
Viruses 2019, 11(3), 277; https://doi.org/10.3390/v11030277
Received: 19 February 2019 / Revised: 14 March 2019 / Accepted: 16 March 2019 / Published: 19 March 2019
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Abstract
In agriculture, the prevention and treatment of bacterial infections represents an increasing challenge. Traditional (chemical) methods have been restricted to ensure public health and to limit the occurrence of resistant strains. Bacteriophages could be a sustainable alternative. A major hurdle towards the commercial [...] Read more.
In agriculture, the prevention and treatment of bacterial infections represents an increasing challenge. Traditional (chemical) methods have been restricted to ensure public health and to limit the occurrence of resistant strains. Bacteriophages could be a sustainable alternative. A major hurdle towards the commercial implementation of phage-based biocontrol strategies concerns aspects of regulation and intellectual property protection. Within this study, two datasets have been composed to analyze both scientific publications and patent documents and to get an idea on the focus of research and development (R&D) by means of an abstract and claim analysis. A total of 137 papers and 49 patent families were found from searching public databases, with their numbers increasing over time. Within this dataset, the majority of the patent documents were filed by non-profit organizations in Asia. There seems to be a good correlation between the papers and patent documents in terms of targeted bacterial genera. Furthermore, granted patents seem to claim rather broad and cover methods of treatment. This review shows that there is indeed growing publishing and patenting activity concerning phage biocontrol. Targeted research is needed to further stimulate the exploration of phages within integrated pest management strategies and to deal with bacterial infections in crop production. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessCommunication
Processing Phage Therapy Requests in a Brussels Military Hospital: Lessons Identified
Viruses 2019, 11(3), 265; https://doi.org/10.3390/v11030265
Received: 19 February 2019 / Revised: 10 March 2019 / Accepted: 14 March 2019 / Published: 17 March 2019
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Abstract
There is a growing interest in phage therapy as a complementary tool against antimicrobial resistant infections. Since 2007, phages have been used sporadically to treat bacterial infections in well-defined cases in the Queen Astrid military hospital (QAMH) in Brussels, Belgium. In the last [...] Read more.
There is a growing interest in phage therapy as a complementary tool against antimicrobial resistant infections. Since 2007, phages have been used sporadically to treat bacterial infections in well-defined cases in the Queen Astrid military hospital (QAMH) in Brussels, Belgium. In the last two years, external requests for phage therapy have increased significantly. From April 2013 to April 2018, 260 phage therapy requests were addressed to the QAMH. Of these 260 requests, only 15 patients received phage therapy. In this paper, we analyze the phage therapy requests and outcomes in order to improve upon the overall capacity for phage therapy at the QAMH. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessArticle
Design and Preclinical Development of a Phage Product for the Treatment of Antibiotic-Resistant Staphylococcus aureus Infections
Viruses 2019, 11(1), 88; https://doi.org/10.3390/v11010088
Received: 20 December 2018 / Revised: 14 January 2019 / Accepted: 16 January 2019 / Published: 21 January 2019
Cited by 1 | PDF Full-text (1960 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bacteriophages, viruses that only kill specific bacteria, are receiving substantial attention as nontraditional antibacterial agents that may help alleviate the growing antibiotic resistance problem in medicine. We describe the design and preclinical development of AB-SA01, a fixed-composition bacteriophage product intended to treat Staphylococcus [...] Read more.
Bacteriophages, viruses that only kill specific bacteria, are receiving substantial attention as nontraditional antibacterial agents that may help alleviate the growing antibiotic resistance problem in medicine. We describe the design and preclinical development of AB-SA01, a fixed-composition bacteriophage product intended to treat Staphylococcus aureus infections. AB-SA01 contains three naturally occurring, obligately lytic myoviruses related to Staphylococcus phage K. AB-SA01 component phages have been sequenced and contain no identifiable bacterial virulence or antibiotic resistance genes. In vitro, AB-SA01 killed 94.5% of 401 clinical Staphylococcus aureus isolates, including methicillin-resistant and vancomycin-intermediate ones for a total of 95% of the 205 known multidrug-resistant isolates. The spontaneous frequency of resistance to AB-SA01 was ≤3 × 10−9, and resistance emerging to one component phage could be complemented by the activity of another component phage. In both neutropenic and immunocompetent mouse models of acute pneumonia, AB-SA01 reduced lung S. aureus populations equivalently to vancomycin. Overall, the inherent characteristics of AB-SA01 component phages meet regulatory and generally accepted criteria for human use, and the preclinical data presented here have supported production under good manufacturing practices and phase 1 clinical studies with AB-SA01. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessArticle
Enterococcus faecalis Countermeasures Defeat a Virulent Picovirinae Bacteriophage
Viruses 2019, 11(1), 48; https://doi.org/10.3390/v11010048
Received: 14 December 2018 / Revised: 29 December 2018 / Accepted: 31 December 2018 / Published: 10 January 2019
Cited by 1 | PDF Full-text (4251 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Enterococcus faecalis is an opportunistic pathogen that has emerged as a major cause of nosocomial infections worldwide. Many clinical strains are indeed resistant to last resort antibiotics and there is consequently a reawakening of interest in exploiting virulent phages to combat them. However, [...] Read more.
Enterococcus faecalis is an opportunistic pathogen that has emerged as a major cause of nosocomial infections worldwide. Many clinical strains are indeed resistant to last resort antibiotics and there is consequently a reawakening of interest in exploiting virulent phages to combat them. However, little is still known about phage receptors and phage resistance mechanisms in enterococci. We made use of a prophageless derivative of the well-known clinical strain E. faecalis V583 to isolate a virulent phage belonging to the Picovirinae subfamily and to the P68 genus that we named Idefix. Interestingly, most isolates of E. faecalis tested—including V583—were resistant to this phage and we investigated more deeply into phage resistance mechanisms. We found that E. faecalis V583 prophage 6 was particularly efficient in resisting Idefix infection thanks to a new abortive infection (Abi) mechanism, which we designated Abiα. It corresponded to the Pfam domain family with unknown function DUF4393 and conferred a typical Abi phenotype by causing a premature lysis of infected E. faecalis. The abiα gene is widespread among prophages of enterococci and other Gram-positive bacteria. Furthermore, we identified two genes involved in the synthesis of the side chains of the surface rhamnopolysaccharide that are important for Idefix adsorption. Interestingly, mutants in these genes arose at a frequency of ~10−4 resistant mutants per generation, conferring a supplemental bacterial line of defense against Idefix. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessArticle
Antibiotic Therapy Using Phage Depolymerases: Robustness Across a Range of Conditions
Viruses 2018, 10(11), 622; https://doi.org/10.3390/v10110622
Received: 26 October 2018 / Revised: 9 November 2018 / Accepted: 10 November 2018 / Published: 12 November 2018
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Abstract
Phage-derived depolymerases directed against bacterial capsules are showing therapeutic promise in various animal models of infection. However, individual animal model studies are often constrained by use of highly specific protocols, such that results may not generalize to even slight modifications. Here we explore [...] Read more.
Phage-derived depolymerases directed against bacterial capsules are showing therapeutic promise in various animal models of infection. However, individual animal model studies are often constrained by use of highly specific protocols, such that results may not generalize to even slight modifications. Here we explore the robustness of depolymerase therapies shown to succeed in a previous study of mice. Treatment success rates were reduced by treatment delay, more so for some enzymes than others: K1- and K5 capsule-degrading enzymes retained partial efficacy on delay, while K30 depolymerase did not. Phage were superior to enzymes under delayed treatment only for K1. Route of administration (intramuscular versus intraperitoneal) mattered for success of K1E, possibly for K1F, not for K1H depolymerase. Significantly, K1 capsule-degrading enzymes proved highly successful when using immune-suppressed, leukopenic mice, even with delayed treatment. Evolution of bacteria resistant to K1-degrading enzymes did not thwart therapeutic success in leukopenic mice, likely because resistant bacteria were avirulent. In combination with previous studies these results continue to support the efficacy of depolymerases as antibacterial agents in vivo, but system-specific details are becoming evident. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessArticle
Characterizing Phage Genomes for Therapeutic Applications
Viruses 2018, 10(4), 188; https://doi.org/10.3390/v10040188
Received: 13 March 2018 / Revised: 6 April 2018 / Accepted: 9 April 2018 / Published: 10 April 2018
Cited by 7 | PDF Full-text (10429 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Multi-drug resistance is increasing at alarming rates. The efficacy of phage therapy, treating bacterial infections with bacteriophages alone or in combination with traditional antibiotics, has been demonstrated in emergency cases in the United States and in other countries, however remains to be approved [...] Read more.
Multi-drug resistance is increasing at alarming rates. The efficacy of phage therapy, treating bacterial infections with bacteriophages alone or in combination with traditional antibiotics, has been demonstrated in emergency cases in the United States and in other countries, however remains to be approved for wide-spread use in the US. One limiting factor is a lack of guidelines for assessing the genomic safety of phage candidates. We present the phage characterization workflow used by our team to generate data for submitting phages to the Federal Drug Administration (FDA) for authorized use. Essential analysis checkpoints and warnings are detailed for obtaining high-quality genomes, excluding undesirable candidates, rigorously assessing a phage genome for safety and evaluating sequencing contamination. This workflow has been developed in accordance with community standards for high-throughput sequencing of viral genomes as well as principles for ideal phages used for therapy. The feasibility and utility of the pipeline is demonstrated on two new phage genomes that meet all safety criteria. We propose these guidelines as a minimum standard for phages being submitted to the FDA for review as investigational new drug candidates. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessArticle
Rapid Identification of Intact Staphylococcal Bacteriophages Using Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry
Viruses 2018, 10(4), 176; https://doi.org/10.3390/v10040176
Received: 13 March 2018 / Revised: 1 April 2018 / Accepted: 2 April 2018 / Published: 4 April 2018
Cited by 4 | PDF Full-text (1152 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Staphylococcus aureus is a major causative agent of infections associated with hospital environments, where antibiotic-resistant strains have emerged as a significant threat. Phage therapy could offer a safe and effective alternative to antibiotics. Phage preparations should comply with quality and safety requirements; therefore, [...] Read more.
Staphylococcus aureus is a major causative agent of infections associated with hospital environments, where antibiotic-resistant strains have emerged as a significant threat. Phage therapy could offer a safe and effective alternative to antibiotics. Phage preparations should comply with quality and safety requirements; therefore, it is important to develop efficient production control technologies. This study was conducted to develop and evaluate a rapid and reliable method for identifying staphylococcal bacteriophages, based on detecting their specific proteins using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling that is among the suggested methods for meeting the regulations of pharmaceutical authorities. Five different phage purification techniques were tested in combination with two MALDI-TOF MS matrices. Phages, either purified by CsCl density gradient centrifugation or as resuspended phage pellets, yielded mass spectra with the highest information value if ferulic acid was used as the MALDI matrix. Phage tail and capsid proteins yielded the strongest signals whereas the culture conditions had no effect on mass spectral quality. Thirty-seven phages from Myoviridae, Siphoviridae or Podoviridae families were analysed, including 23 siphophages belonging to the International Typing Set for human strains of S. aureus, as well as phages in preparations produced by Microgen, Bohemia Pharmaceuticals and MB Pharma. The data obtained demonstrate that MALDI-TOF MS can be used to effectively distinguish between Staphylococcus-specific bacteriophages. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessCommunication
The Magistral Phage
Viruses 2018, 10(2), 64; https://doi.org/10.3390/v10020064
Received: 15 January 2018 / Revised: 2 February 2018 / Accepted: 3 February 2018 / Published: 6 February 2018
Cited by 28 | PDF Full-text (348 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Since time immemorial, phages—the viral parasites of bacteria—have been protecting Earth’s biosphere against bacterial overgrowth. Today, phages could help address the antibiotic resistance crisis that affects all of society. The greatest hurdle to the introduction of phage therapy in Western medicine is the [...] Read more.
Since time immemorial, phages—the viral parasites of bacteria—have been protecting Earth’s biosphere against bacterial overgrowth. Today, phages could help address the antibiotic resistance crisis that affects all of society. The greatest hurdle to the introduction of phage therapy in Western medicine is the lack of an appropriate legal and regulatory framework. Belgium is now implementing a pragmatic phage therapy framework that centers on the magistral preparation (compounding pharmacy in the US) of tailor-made phage medicines. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessArticle
Characterization of vB_SauM-fRuSau02, a Twort-Like Bacteriophage Isolated from a Therapeutic Phage Cocktail
Viruses 2017, 9(9), 258; https://doi.org/10.3390/v9090258
Received: 29 June 2017 / Revised: 29 August 2017 / Accepted: 11 September 2017 / Published: 14 September 2017
Cited by 6 | PDF Full-text (5329 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Staphylococcus aureus is a commensal and pathogenic bacterium that causes infections in humans and animals. It is a major cause of nosocomial infections worldwide. Due to increasing prevalence of multidrug resistance, alternative methods to eradicate the pathogen are necessary. In this respect, polyvalent [...] Read more.
Staphylococcus aureus is a commensal and pathogenic bacterium that causes infections in humans and animals. It is a major cause of nosocomial infections worldwide. Due to increasing prevalence of multidrug resistance, alternative methods to eradicate the pathogen are necessary. In this respect, polyvalent staphylococcal myoviruses have been demonstrated to be excellent candidates for phage therapy. Here we present the characterization of the bacteriophage vB_SauM-fRuSau02 (fRuSau02) that was isolated from a commercial Staphylococcus bacteriophage cocktail produced by Microgen (Moscow, Russia). The genomic analysis revealed that fRuSau02 is very closely related to the phage MSA6, and possesses a large genome (148,464 bp), with typical modular organization and a low G+C (30.22%) content. It can therefore be classified as a new virus among the genus Twortlikevirus. The genome contains 236 predicted genes, 4 of which were interrupted by insertion sequences. Altogether, 78 different structural and virion-associated proteins were identified from purified phage particles by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The host range of fRuSau02 was tested with 135 strains, including 51 and 54 Staphylococcus aureus isolates from humans and pigs, respectively, and 30 coagulase-negative Staphylococcus strains of human origin. All clinical S. aureus strains were at least moderately sensitive to the phage, while only 39% of the pig strains were infected. Also, some strains of Staphylococcus intermedius, Staphylococcus lugdunensis, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus saprophyticus and Staphylococcus pseudointer were sensitive. We conclude that fRuSau02, a phage therapy agent in Russia, can serve as an alternative to antibiotic therapy against S. aureus. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Review

Jump to: Research, Other

Open AccessReview
Evaluation of Phage Therapy in the Context of Enterococcus faecalis and Its Associated Diseases
Viruses 2019, 11(4), 366; https://doi.org/10.3390/v11040366
Received: 19 March 2019 / Revised: 16 April 2019 / Accepted: 17 April 2019 / Published: 20 April 2019
PDF Full-text (7794 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bacteriophages (phages) or bacterial viruses have been proposed as natural antimicrobial agents to fight against antibiotic-resistant bacteria associated with human infections. Enterococcus faecalis is a gut commensal, which is occasionally found in the mouth and vaginal tract, and does not usually cause clinical [...] Read more.
Bacteriophages (phages) or bacterial viruses have been proposed as natural antimicrobial agents to fight against antibiotic-resistant bacteria associated with human infections. Enterococcus faecalis is a gut commensal, which is occasionally found in the mouth and vaginal tract, and does not usually cause clinical problems. However, it can spread to other areas of the body and cause life-threatening infections, such as septicemia, endocarditis, or meningitis, in immunocompromised hosts. Although E. faecalis phage cocktails are not commercially available within the EU or USA, there is an accumulated evidence from in vitro and in vivo studies that have shown phage efficacy, which supports the idea of applying phage therapy to overcome infections associated with E. faecalis. In this review, we discuss the potency of bacteriophages in controlling E. faecalis, in both in vitro and in vivo scenarios. E. faecalis associated bacteriophages were compared at the genome level and an attempt was made to categorize phages with respect to their suitability for therapeutic application, using orthocluster analysis. In addition, E. faecalis phages have been examined for the presence of antibiotic-resistant genes, to ensure their safe use in clinical conditions. Finally, the domain architecture of E. faecalis phage-encoded endolysins are discussed. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessReview
Current State of Compassionate Phage Therapy
Viruses 2019, 11(4), 343; https://doi.org/10.3390/v11040343
Received: 1 March 2019 / Revised: 4 April 2019 / Accepted: 6 April 2019 / Published: 12 April 2019
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Abstract
There is a current unmet medical need for the treatment of antibiotic-resistant infections, and in the absence of approved alternatives, some clinicians are turning to empirical ones, such as phage therapy, for compassionate treatment. Phage therapy is ideal for compassionate use due to [...] Read more.
There is a current unmet medical need for the treatment of antibiotic-resistant infections, and in the absence of approved alternatives, some clinicians are turning to empirical ones, such as phage therapy, for compassionate treatment. Phage therapy is ideal for compassionate use due to its long-standing historical use and publications, apparent lack of adverse effects, and solid support by fundamental research. Increased media coverage and peer-reviewed articles have given rise to a more widespread familiarity with its therapeutic potential. However, compassionate phage therapy (cPT) remains limited to a small number of experimental treatment centers or associated with individual physicians and researchers. It is possible, with the creation of guidelines and a greater central coordination, that cPT could reach more of those in need, starting by increasing the availability of phages. Subsequent steps, particularly production and purification, are difficult to scale, and treatment paradigms stand highly variable between cases, or are frequently not reported. This article serves both to synopsize cPT publications to date and to discuss currently available phage sources for cPT. As the antibiotic resistance crisis continues to grow and the future of phage therapy clinical trials remains undetermined, cPT represents a possibility for bridging the gap between current treatment failures and future approved alternatives. Streamlining the process of cPT will help to ensure high quality, therapeutically-beneficial, and safe treatment. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessReview
Towards Inhaled Phage Therapy in Western Europe
Viruses 2019, 11(3), 295; https://doi.org/10.3390/v11030295
Received: 15 February 2019 / Revised: 12 March 2019 / Accepted: 20 March 2019 / Published: 23 March 2019
PDF Full-text (253 KB) | HTML Full-text | XML Full-text
Abstract
The emergence of multidrug-resistant bacteria constitutes a great challenge for modern medicine, recognized by leading medical experts and politicians worldwide. Rediscovery and implementation of bacteriophage therapy by Western medicine might be one solution to the problem of increasing antibiotic failure. In some Eastern [...] Read more.
The emergence of multidrug-resistant bacteria constitutes a great challenge for modern medicine, recognized by leading medical experts and politicians worldwide. Rediscovery and implementation of bacteriophage therapy by Western medicine might be one solution to the problem of increasing antibiotic failure. In some Eastern European countries phage therapy is used for treating infectious diseases. However, while the European Medicines Agency (EMA) advised that the development of bacteriophage-based therapies should be expedited due to its significant potential, EMA emphasized that phages cannot be recommended for approval before efficacy and safety have been proven by appropriately designed preclinical and clinical trials. More evidence-based data is required, particularly in the areas of pharmacokinetics, repeat applications, immunological reactions to the application of phages as well as the interactions and effects on bacterial biofilms and organ-specific environments. In this brief review we summarize advantages and disadvantages of phage therapy and discuss challenges to the establishment of phage therapy as approved treatment for multidrug-resistant bacteria. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
Open AccessReview
Interactions between Bacteriophage, Bacteria, and the Mammalian Immune System
Viruses 2019, 11(1), 10; https://doi.org/10.3390/v11010010
Received: 4 December 2018 / Revised: 19 December 2018 / Accepted: 21 December 2018 / Published: 25 December 2018
Cited by 3 | PDF Full-text (4144 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The human body is host to large numbers of bacteriophages (phages)–a diverse group of bacterial viruses that infect bacteria. Phage were previously regarded as bystanders that only impacted immunity indirectly via effects on the mammalian microbiome. However, it has become clear that phages [...] Read more.
The human body is host to large numbers of bacteriophages (phages)–a diverse group of bacterial viruses that infect bacteria. Phage were previously regarded as bystanders that only impacted immunity indirectly via effects on the mammalian microbiome. However, it has become clear that phages also impact immunity directly, in ways that are typically anti-inflammatory. Phages can modulate innate immunity via phagocytosis and cytokine responses, but also impact adaptive immunity via effects on antibody production and effector polarization. Phages may thereby have profound effects on the outcome of bacterial infections by modulating the immune response. In this review we highlight the diverse ways in which phages interact with human cells. We present a computational model for predicting these complex and dynamic interactions. These models predict that the phageome may play important roles in shaping mammalian-bacterial interactions. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessReview
Resistance Development to Bacteriophages Occurring during Bacteriophage Therapy
Viruses 2018, 10(7), 351; https://doi.org/10.3390/v10070351
Received: 10 June 2018 / Revised: 27 June 2018 / Accepted: 28 June 2018 / Published: 30 June 2018
Cited by 5 | PDF Full-text (280 KB) | HTML Full-text | XML Full-text
Abstract
Bacteriophage (phage) therapy, i.e., the use of viruses that infect bacteria as antimicrobial agents, is a promising alternative to conventional antibiotics. Indeed, resistance to antibiotics has become a major public health problem after decades of extensive usage. However, one of the main questions [...] Read more.
Bacteriophage (phage) therapy, i.e., the use of viruses that infect bacteria as antimicrobial agents, is a promising alternative to conventional antibiotics. Indeed, resistance to antibiotics has become a major public health problem after decades of extensive usage. However, one of the main questions regarding phage therapy is the possible rapid emergence of phage-resistant bacterial variants, which could impede favourable treatment outcomes. Experimental data has shown that phage-resistant variants occurred in up to 80% of studies targeting the intestinal milieu and 50% of studies using sepsis models. Phage-resistant variants have also been observed in human studies, as described in three out of four clinical trials that recorded the emergence of phage resistance. On the other hand, recent animal studies suggest that bacterial mutations that confer phage-resistance may result in fitness costs in the resistant bacterium, which, in turn, could benefit the host. Thus, phage resistance should not be underestimated and efforts should be made to develop methodologies for monitoring and preventing it. Moreover, understanding and taking advantage of the resistance-induced fitness costs in bacterial pathogens is a potentially promising avenue. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
Open AccessReview
Delivering Phage Products to Combat Antibiotic Resistance in Developing Countries: Lessons Learned from the HIV/AIDS Epidemic in Africa
Viruses 2018, 10(7), 345; https://doi.org/10.3390/v10070345
Received: 30 May 2018 / Revised: 24 June 2018 / Accepted: 26 June 2018 / Published: 27 June 2018
PDF Full-text (528 KB) | HTML Full-text | XML Full-text
Abstract
The antimicrobial resistance (AMR) crisis and HIV/AIDS epidemic exhibit many parallels. In both, infectious diseases have caused millions of deaths worldwide, with AMR expected to kill even more people each year than HIV/AIDS did at its peak. In addition, both have required or [...] Read more.
The antimicrobial resistance (AMR) crisis and HIV/AIDS epidemic exhibit many parallels. In both, infectious diseases have caused millions of deaths worldwide, with AMR expected to kill even more people each year than HIV/AIDS did at its peak. In addition, both have required or will require new classes of drugs for control. For HIV/AIDS, development of vital antiretroviral drugs (ARVs) was accomplished in several stages: expanding public awareness about the disease, gathering commitment from the international community to tackle the problem, and eventually establishing policies and global funds to deliver new therapeutics. For AMR, the pursuit of new antimicrobials appears to be following a similar trajectory. This paper examines how lessons and processes leading to ARVs might be applied to developing AMR drugs, in particular bacteriophages (phages). These possess many essential characteristics: inexpensive manufacture, rapid drug development, and a ready means to prevent phage-resistant microbes from emerging. However, the broad application of phage-based products has yet to be fully demonstrated, and will require both international coordination and modified regulatory policies. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessReview
The Diversity of Bacterial Lifestyles Hampers Bacteriophage Tenacity
Viruses 2018, 10(6), 327; https://doi.org/10.3390/v10060327
Received: 18 May 2018 / Revised: 8 June 2018 / Accepted: 11 June 2018 / Published: 15 June 2018
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Abstract
Phage therapy is based on a simple concept: the use of a virus (bacteriophage) that is capable of killing specific pathogenic bacteria to treat bacterial infections. Since the pioneering work of Félix d’Herelle, bacteriophages (phages) isolated in vitro have been shown to be [...] Read more.
Phage therapy is based on a simple concept: the use of a virus (bacteriophage) that is capable of killing specific pathogenic bacteria to treat bacterial infections. Since the pioneering work of Félix d’Herelle, bacteriophages (phages) isolated in vitro have been shown to be of therapeutic value. Over decades of study, a large number of rather complex mechanisms that are used by phages to hijack bacterial resources and to produce their progeny have been deciphered. While these mechanisms have been identified and have been studied under optimal conditions in vitro, much less is known about the requirements for successful viral infections in relevant natural conditions. This is particularly true in the context of phage therapy. Here, we highlight the parameters affecting phage replication in both in vitro and in vivo environments, focusing, in particular, on the mammalian digestive tract. We propose avenues for increasing the knowledge-guided implementation of phages as therapeutic tools. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessReview
Phage Therapy: What Have We Learned?
Viruses 2018, 10(6), 288; https://doi.org/10.3390/v10060288
Received: 18 April 2018 / Revised: 11 May 2018 / Accepted: 22 May 2018 / Published: 28 May 2018
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Abstract
In this article we explain how current events in the field of phage therapy may positively influence its future development. We discuss the shift in position of the authorities, academia, media, non-governmental organizations, regulatory agencies, patients, and doctors which could enable further advances [...] Read more.
In this article we explain how current events in the field of phage therapy may positively influence its future development. We discuss the shift in position of the authorities, academia, media, non-governmental organizations, regulatory agencies, patients, and doctors which could enable further advances in the research and application of the therapy. In addition, we discuss methods to obtain optimal phage preparations and suggest the potential of novel applications of phage therapy extending beyond its anti-bacterial action. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessReview
Framing the Future with Bacteriophages in Agriculture
Viruses 2018, 10(5), 218; https://doi.org/10.3390/v10050218
Received: 27 March 2018 / Revised: 20 April 2018 / Accepted: 22 April 2018 / Published: 25 April 2018
Cited by 5 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
The ability of agriculture to continually provide food to a growing world population is of crucial importance. Bacterial diseases of plants and animals have continually reduced production since the advent of crop cultivation and animal husbandry practices. Antibiotics have been used extensively to [...] Read more.
The ability of agriculture to continually provide food to a growing world population is of crucial importance. Bacterial diseases of plants and animals have continually reduced production since the advent of crop cultivation and animal husbandry practices. Antibiotics have been used extensively to mitigate these losses. The rise of antimicrobial resistant (AMR) bacteria, however, together with consumers’ calls for antibiotic-free products, presents problems that threaten sustainable agriculture. Bacteriophages (phages) are proposed as bacterial population control alternatives to antibiotics. Their unique properties make them highly promising but challenging antimicrobials. The use of phages in agriculture also presents a number of unique challenges. This mini-review summarizes recent development and perspectives of phages used as antimicrobial agents in plant and animal agriculture at the farm level. The main pathogens and their adjoining phage therapies are discussed. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
Open AccessReview
Bacteriophage Applications for Food Production and Processing
Viruses 2018, 10(4), 205; https://doi.org/10.3390/v10040205
Received: 19 March 2018 / Revised: 10 April 2018 / Accepted: 11 April 2018 / Published: 19 April 2018
Cited by 12 | PDF Full-text (352 KB) | HTML Full-text | XML Full-text
Abstract
Foodborne illnesses remain a major cause of hospitalization and death worldwide despite many advances in food sanitation techniques and pathogen surveillance. Traditional antimicrobial methods, such as pasteurization, high pressure processing, irradiation, and chemical disinfectants are capable of reducing microbial populations in foods to [...] Read more.
Foodborne illnesses remain a major cause of hospitalization and death worldwide despite many advances in food sanitation techniques and pathogen surveillance. Traditional antimicrobial methods, such as pasteurization, high pressure processing, irradiation, and chemical disinfectants are capable of reducing microbial populations in foods to varying degrees, but they also have considerable drawbacks, such as a large initial investment, potential damage to processing equipment due to their corrosive nature, and a deleterious impact on organoleptic qualities (and possibly the nutritional value) of foods. Perhaps most importantly, these decontamination strategies kill indiscriminately, including many—often beneficial—bacteria that are naturally present in foods. One promising technique that addresses several of these shortcomings is bacteriophage biocontrol, a green and natural method that uses lytic bacteriophages isolated from the environment to specifically target pathogenic bacteria and eliminate them from (or significantly reduce their levels in) foods. Since the initial conception of using bacteriophages on foods, a substantial number of research reports have described the use of bacteriophage biocontrol to target a variety of bacterial pathogens in various foods, ranging from ready-to-eat deli meats to fresh fruits and vegetables, and the number of commercially available products containing bacteriophages approved for use in food safety applications has also been steadily increasing. Though some challenges remain, bacteriophage biocontrol is increasingly recognized as an attractive modality in our arsenal of tools for safely and naturally eliminating pathogenic bacteria from foods. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
Open AccessReview
Criteria for Selecting Suitable Infectious Diseases for Phage Therapy
Viruses 2018, 10(4), 177; https://doi.org/10.3390/v10040177
Received: 16 March 2018 / Revised: 30 March 2018 / Accepted: 30 March 2018 / Published: 5 April 2018
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Abstract
One of the main issues with phage therapy from its earliest days has been the selection of appropriate disease targets. In early work, when the nature of bacteriophages was unknown, many inappropriate targets were selected, including some now known to have no bacterial [...] Read more.
One of the main issues with phage therapy from its earliest days has been the selection of appropriate disease targets. In early work, when the nature of bacteriophages was unknown, many inappropriate targets were selected, including some now known to have no bacterial involvement whatsoever. More recently, with greatly increased understanding of the highly specific nature of bacteriophages and of their mechanisms of action, it has been possible to select indications with an increased chance of a successful therapeutic outcome. The factors to be considered include the characteristics of the infection to be treated, the characteristics of the bacteria involved, and the characteristics of the bacteriophages themselves. At a later stage all of this information then informs trial design and regulatory considerations. Where the work is undertaken towards the development of a commercial product it is also necessary to consider the planned market, protection of intellectual property, and the sourcing of funding to support the work. It is clear that bacteriophages are not a “magic bullet”. However, with careful and appropriate selection of a limited set of initial targets, it should be possible to obtain proof of concept for the many elements required for the success of phage therapy. In time, success with these initial targets could then support more widespread use. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessReview
In Vitro Characteristics of Phages to Guide ‘Real Life’ Phage Therapy Suitability
Viruses 2018, 10(4), 163; https://doi.org/10.3390/v10040163
Received: 14 March 2018 / Revised: 27 March 2018 / Accepted: 29 March 2018 / Published: 30 March 2018
Cited by 5 | PDF Full-text (687 KB) | HTML Full-text | XML Full-text
Abstract
The increasing problem of antibiotic-resistant pathogens has put enormous pressure on healthcare providers to reduce the application of antibiotics and to identify alternative therapies. Phages represent such an alternative with significant application potential, either on their own or in combination with antibiotics to [...] Read more.
The increasing problem of antibiotic-resistant pathogens has put enormous pressure on healthcare providers to reduce the application of antibiotics and to identify alternative therapies. Phages represent such an alternative with significant application potential, either on their own or in combination with antibiotics to enhance the effectiveness of traditional therapies. However, while phage therapy may offer exciting therapeutic opportunities, its evaluation for safe and appropriate use in humans needs to be guided initially by reliable and appropriate assessment techniques at the laboratory level. Here, we review the process of phage isolation and the application of individual pathogens or reference collections for the development of specific or “off-the-shelf” preparations. Furthermore, we evaluate current characterization approaches to assess the in vitro therapeutic potential of a phage including its spectrum of activity, genome characteristics, storage and administration requirements and effectiveness against biofilms. Lytic characteristics and the ability to overcome anti-phage systems are also covered. These attributes direct phage selection for their ultimate application as antimicrobial agents. We also discuss current pitfalls in this research area and propose that priority should be given to unify current phage characterization approaches. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessOpinion
Phage Therapy Regulation: From Night to Dawn
Viruses 2019, 11(4), 352; https://doi.org/10.3390/v11040352
Received: 28 February 2019 / Revised: 23 March 2019 / Accepted: 7 April 2019 / Published: 17 April 2019
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Abstract
After decades of disregard in the Western world, phage therapy is witnessing a return of interest. However, the pharmaceutical legislation that has since been implemented is basically designed for regulating industrially-made pharmaceuticals, devoid of any patient customization and intended for large-scale distribution. Accordingly, [...] Read more.
After decades of disregard in the Western world, phage therapy is witnessing a return of interest. However, the pharmaceutical legislation that has since been implemented is basically designed for regulating industrially-made pharmaceuticals, devoid of any patient customization and intended for large-scale distribution. Accordingly, the resulting regulatory framework is hardly reconcilable with the concept of sustainable phage therapy, involving tailor-made medicinal products in the global perspective of both evolutionary and personalized medicine. The repeated appeal for a dedicated regulatory framework has not been heard by the European legislature, which, in this matter, features a strong resistance to change despite the precedent of the unhindered implementation of advanced therapy medicinal product (ATMPs) regulation. It is acknowledged that in many aspects, phage therapy medicinal products are quite unconventional pharmaceuticals and likely this lack of conformity to the canonical model hampered the development of a suitable regulatory pathway. However, the regulatory approaches of countries where phage therapy traditions and practice have never been abandoned are now being revisited by some Western countries, opening new avenues for phage therapy regulation. As a next step, supranational and international organizations are urged to take over the initiatives originally launched by national regulatory authorities. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
Open AccessOpinion
Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections
Viruses 2019, 11(1), 18; https://doi.org/10.3390/v11010018
Received: 27 November 2018 / Revised: 18 December 2018 / Accepted: 21 December 2018 / Published: 28 December 2018
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Abstract
The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for [...] Read more.
The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists between trials and compassionate use in order to better develop future phage treatment and clinical applications. The multitude of observations reported over the years in the literature constitutes an invaluable experience, and we add to this by presenting a number of cases of patients treated compassionately with phages throughout the past decade with a focus on osteoarticular infections. Additionally, an abundance of scientific literature into phage-related areas is transforming our knowledge base, creating a greater understanding that should be applied for future clinical applications. Due to the increasing number of treatment failures anticipatedfrom the perspective of a possible post-antibiotic era, we believe that the introduction of bacteriophages into the therapeutic arsenal seems a scientifically sound and eminently practicable consideration today as a substitute or adjuvant to antibiotic therapy. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
Open AccessBrief Report
Production of Bacteriophages by Listeria Cells Entrapped in Organic Polymers
Viruses 2018, 10(6), 324; https://doi.org/10.3390/v10060324
Received: 13 May 2018 / Revised: 7 June 2018 / Accepted: 8 June 2018 / Published: 13 June 2018
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Abstract
Applications for bacteriophages as antimicrobial agents are increasing. The industrial use of these bacterial viruses requires the production of large amounts of suitable strictly lytic phages, particularly for food and agricultural applications. This work describes a new approach for phage production. Phages H387 [...] Read more.
Applications for bacteriophages as antimicrobial agents are increasing. The industrial use of these bacterial viruses requires the production of large amounts of suitable strictly lytic phages, particularly for food and agricultural applications. This work describes a new approach for phage production. Phages H387 (Siphoviridae) and A511 (Myoviridae) were propagated separately using Listeria ivanovii host cells immobilised in alginate beads. The same batch of alginate beads could be used for four successive and efficient phage productions. This technique enables the production of large volumes of high-titer phage lysates in continuous or semi-continuous (fed-batch) cultures. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessComment
Phage Therapy Faces Evolutionary Challenges
Viruses 2018, 10(6), 323; https://doi.org/10.3390/v10060323
Received: 18 May 2018 / Revised: 9 June 2018 / Accepted: 12 June 2018 / Published: 12 June 2018
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Abstract
Antibiotic resistance evolution in bacteria indicates that one of the challenges faced by phage therapy is that, sooner or later, bacteria will evolve resistance to phages. Evidently, this is the case of every known antimicrobial therapy, but here this is also part of [...] Read more.
Antibiotic resistance evolution in bacteria indicates that one of the challenges faced by phage therapy is that, sooner or later, bacteria will evolve resistance to phages. Evidently, this is the case of every known antimicrobial therapy, but here this is also part of a ubiquitous natural process of co-evolution between phages and bacteria. Fundamental evolutionary studies hold some clues that are crucial to limit the problematic process of bacterial resistance during phage applications. First, I discuss here the importance of defining evolutionary and ecological factors influencing bacterial resistance and phage counter-defense mechanisms. Then, I comment on the interest of determining the co-evolutionary dynamics between phages and bacteria that may allow for selecting the conditions that will increase the probability of therapeutic success. I go on to suggest the varied strategies that may ensure the long-term success of phage therapy, including analysis of internal phage parameters and personalized treatments. In practical terms, these types of approaches will define evolutionary criteria regarding how to develop, and when to apply, therapeutic phage cocktails. Integrating this perspective in antimicrobial treatments, such as phage therapy, is among the necessary steps to expand its use in the near future, and to ensure its durability and success. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessComment
Phages Make for Jolly Good Stories
Viruses 2018, 10(4), 209; https://doi.org/10.3390/v10040209
Received: 12 March 2018 / Revised: 15 April 2018 / Accepted: 19 April 2018 / Published: 20 April 2018
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Abstract
Phage therapy has an intriguing history. It was widely used from the 1920s until the 1940s. After this period, it was nearly completely forgotten in the Western world, while it continued to be used in the Soviet part of the globe. The study [...] Read more.
Phage therapy has an intriguing history. It was widely used from the 1920s until the 1940s. After this period, it was nearly completely forgotten in the Western world, while it continued to be used in the Soviet part of the globe. The study of the history of phage therapy provides valuable input into the present development of the field. Science journalists uncovered much of this history and played an important role in the communication of phage therapy after the fall of the Soviet Union, when it came to the attention of Western researchers and doctors. This interest was fueled by the antibiotic resistance crisis. At this time, communication about phage therapy had a wide potential audience, that encompassed medical experts and researchers, as well as the public, because knowledge about this forgotten therapy was very limited. In such a situation, good communication had and still has the potential to catalyze important discussions among different groups; whereas, bad communication could have considerably hindered and still can hinder the possible renaissance of phage therapy. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
Open AccessConference Report
Expert Opinion on Three Phage Therapy Related Topics: Bacterial Phage Resistance, Phage Training and Prophages in Bacterial Production Strains
Viruses 2018, 10(4), 178; https://doi.org/10.3390/v10040178
Received: 31 March 2018 / Revised: 3 April 2018 / Accepted: 3 April 2018 / Published: 5 April 2018
Cited by 10 | PDF Full-text (322 KB) | HTML Full-text | XML Full-text
Abstract
Phage therapy is increasingly put forward as a “new” potential tool in the fight against antibiotic resistant infections. During the “Centennial Celebration of Bacteriophage Research” conference in Tbilisi, Georgia on 26–29 June 2017, an international group of phage researchers committed to elaborate an [...] Read more.
Phage therapy is increasingly put forward as a “new” potential tool in the fight against antibiotic resistant infections. During the “Centennial Celebration of Bacteriophage Research” conference in Tbilisi, Georgia on 26–29 June 2017, an international group of phage researchers committed to elaborate an expert opinion on three contentious phage therapy related issues that are hampering clinical progress in the field of phage therapy. This paper explores and discusses bacterial phage resistance, phage training and the presence of prophages in bacterial production strains while reviewing relevant research findings and experiences. Our purpose is to inform phage therapy stakeholders such as policy makers, officials of the competent authorities for medicines, phage researchers and phage producers, and members of the pharmaceutical industry. This brief also points out potential avenues for future phage therapy research and development as it specifically addresses those overarching questions that currently call for attention whenever phages go into purification processes for application. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
Open AccessBrief Report
Selection of Potential Therapeutic Bacteriophages that Lyse a CTX-M-15 Extended Spectrum β-Lactamase Producing Salmonella enterica Serovar Typhi Strain from the Democratic Republic of the Congo
Viruses 2018, 10(4), 172; https://doi.org/10.3390/v10040172
Received: 9 March 2018 / Revised: 31 March 2018 / Accepted: 2 April 2018 / Published: 3 April 2018
Cited by 3 | PDF Full-text (4060 KB) | HTML Full-text | XML Full-text
Abstract
Recently, a Salmonella Typhi isolate producing CTX-M-15 extended spectrum β-lactamase (ESBL) and with decreased ciprofloxacin susceptibility was isolated in the Democratic Republic of the Congo. We have selected bacteriophages that show strong lytic activity against this isolate and have potential for phage-based treatment [...] Read more.
Recently, a Salmonella Typhi isolate producing CTX-M-15 extended spectrum β-lactamase (ESBL) and with decreased ciprofloxacin susceptibility was isolated in the Democratic Republic of the Congo. We have selected bacteriophages that show strong lytic activity against this isolate and have potential for phage-based treatment of S. Typhi, and Salmonella in general. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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Open AccessConference Report
1st German Phage Symposium—Conference Report
Viruses 2018, 10(4), 158; https://doi.org/10.3390/v10040158
Received: 13 March 2018 / Revised: 23 March 2018 / Accepted: 25 March 2018 / Published: 29 March 2018
Cited by 2 | PDF Full-text (373 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In Germany, phage research and application can be traced back to the beginning of the 20th century. However, with the triumphal march of antibiotics around the world, the significance of bacteriophages faded in most countries, and respective research mainly focused on fundamental questions [...] Read more.
In Germany, phage research and application can be traced back to the beginning of the 20th century. However, with the triumphal march of antibiotics around the world, the significance of bacteriophages faded in most countries, and respective research mainly focused on fundamental questions and niche applications. After a century, we pay tribute to the overuse of antibiotics that led to multidrug resistance and calls for new strategies to combat pathogenic microbes. Against this background, bacteriophages came into the spotlight of researchers and practitioners again resulting in a fast growing “phage community”. In October 2017, part of this community met at the 1st German Phage Symposium to share their knowledge and experiences. The participants discussed open questions and challenges related to phage therapy and the application of phages in general. This report summarizes the presentations given, highlights the main points of the round table discussion and concludes with an outlook for the different aspects of phage application. Full article
(This article belongs to the Special Issue Hurdles for Phage Therapy (PT) to Become a Reality)
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