Antibiotics vs. Phage Therapy

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Bacteriophages".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 36893

Special Issue Editor


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Guest Editor
Department of Molecular Biology, University of Gdańsk, Gdańsk, Poland
Interests: gene expression regulation; DNA replication; bacteriophages; plasmids; human genetic diseases; neurodegeneration
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Special Issue Information

Dear Colleagues,

The antibiotic-resistance crisis demands the development of novel therapeutic approaches. Phage therapy (the use of bacteriophages to combat bacteria) is one of them. However, antibiotics are still important weapons in our fight against pathogenic microorganisms, and must be considered as we assess any novel approaches. This Special Issue is focused on the comparison and interplay between antibiotics and phage therapy. Topics of interest include, but are not limited to, the following issues: (1) comparing the efficacy and safety of antibiotics and phage therapy, (2) the identification and characterization of newly discovered antimicrobial chemical agents and bacteriophages, and (3) assessing the effectiveness of combined therapies using antibiotics together with bacteriophages to combat bacterial infections. Both original papers and review articles are welcome, and will be considered for publication in this Special Issue of Antibiotics.

Prof. Dr. Grzegorz Węgrzyn
Guest Editor

Manuscript Submission Information

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Keywords

  • antibiotic safety
  • antibiotic efficacy
  • bacteriophages
  • phage therapy
  • combination of antibiotic and phage therapies

Published Papers (8 papers)

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Research

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12 pages, 2053 KiB  
Article
Immunogenicity of Endolysin PlyC
by Marek Adam Harhala, Katarzyna Gembara, Daniel C. Nelson, Paulina Miernikiewicz and Krystyna Dąbrowska
Antibiotics 2022, 11(7), 966; https://doi.org/10.3390/antibiotics11070966 - 18 Jul 2022
Cited by 7 | Viewed by 2353
Abstract
Endolysins are bacteriolytic enzymes derived from bacteriophages. They represent an alternative to antibiotics, since they are not susceptible to conventional antimicrobial resistance mechanisms. Since non-human proteins are efficient inducers of specific immune responses, including the IgG response or the development of an allergic [...] Read more.
Endolysins are bacteriolytic enzymes derived from bacteriophages. They represent an alternative to antibiotics, since they are not susceptible to conventional antimicrobial resistance mechanisms. Since non-human proteins are efficient inducers of specific immune responses, including the IgG response or the development of an allergic response mediated by IgE, we evaluated the general immunogenicity of the highly active antibacterial enzyme, PlyC, in a human population and in a mouse model. The study includes the identification of molecular epitopes of PlyC. The overall assessment of potential hypersensitivity to this protein and PlyC-specific IgE testing was also conducted in mice. PlyC induced efficient IgG production in mice, and the molecular analysis revealed that PlyC-specific IgG interacted with four immunogenic regions identified within the PlyCA subunit. In humans, approximately 10% of the population demonstrated IgG reactivity to the PlyCB subunit only, which is attributed to cross-reactions since this was a naïve serum. Of note, in spite of being immunogenic, PlyC induced a normal immune response, without hypersensitivity, since both the animals challenged with PlyC and in the human population PlyC-specific IgE was not detected. Full article
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)
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21 pages, 2041 KiB  
Article
Synergistic Effects of Bacteriophage vB_Eco4-M7 and Selected Antibiotics on the Biofilm Formed by Shiga Toxin-Producing Escherichia coli
by Agnieszka Necel, Sylwia Bloch, Gracja Topka-Bielecka, Agata Janiszewska, Aleksandra Łukasiak, Bożena Nejman-Faleńczyk and Grzegorz Węgrzyn
Antibiotics 2022, 11(6), 712; https://doi.org/10.3390/antibiotics11060712 - 25 May 2022
Cited by 7 | Viewed by 2830
Abstract
Apart from antibiotic resistance of pathogenic bacteria, the formation of biofilms is a feature that makes bacterial infections especially difficulty to treat. Shiga toxin-producing Escherichia coli (STEC) strains are dangerous pathogens, causing severe infections in humans, and capable of biofilm production. We have [...] Read more.
Apart from antibiotic resistance of pathogenic bacteria, the formation of biofilms is a feature that makes bacterial infections especially difficulty to treat. Shiga toxin-producing Escherichia coli (STEC) strains are dangerous pathogens, causing severe infections in humans, and capable of biofilm production. We have reported previously the identification and characterization of the vB_Eco4-M7 bacteriophage, infecting various STEC strains. It was suggested that this phage might be potentially used in phage therapy against these bacteria. Here, we tested the effects of vB_Eco4-M7 alone or in a phage cocktail with another STEC-infecting phage, and/or in a combination with different antibiotics (ciprofloxacin and rifampicin) on biofilm formed by a model STEC strain, named E. coli O157:H7 (ST2-8624). The vB_Eco4-M7 phage appeared effective in anti-biofilm action in all these experimental conditions (2–3-fold reduction of the biofilm density, and 2–3 orders of magnitude reduction of the number of bacterial cells). However, the highest efficiency in reducing a biofilm’s density and number of bacterial cells was observed when phage infection preceded antibiotic treatment (6-fold reduction of the biofilm density, and 5–6 orders of magnitude reduction of the number of bacterial cells). Previous reports indicated that the use of antibiotics to treat STEC-caused infections might be dangerous due to the induction of Shiga toxin-converting prophages from bacterial genomes under stress conditions caused by antibacterial agents. We found that ciprofloxacin was almost as efficient in inducing prophages from the E. coli O15:H7 (ST2-8624) genome as a classical inducer, mitomycin C, while no detectable prophage induction could be observed in rifampicin-treated STEC cells. Therefore, we conclude the latter antibiotic or similarly acting compounds might be candidate(s) as effective and safe drug(s) when used in combination with phage therapy to combat STEC-mediated infections. Full article
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)
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11 pages, 1791 KiB  
Article
Application of Bacteriophages on Shiga Toxin-Producing Escherichia coli (STEC) Biofilm
by Nicola Mangieri, Roberto Foschino and Claudia Picozzi
Antibiotics 2021, 10(11), 1423; https://doi.org/10.3390/antibiotics10111423 - 20 Nov 2021
Cited by 8 | Viewed by 2192
Abstract
Shiga toxin-producing Escherichia coli are pathogenic bacteria able to form biofilms both on abiotic surfaces and on food, thus increasing risks for food consumers. Moreover, biofilms are difficult to remove and more resistant to antimicrobial agents compared to planktonic cells. Bacteriophages, natural predators [...] Read more.
Shiga toxin-producing Escherichia coli are pathogenic bacteria able to form biofilms both on abiotic surfaces and on food, thus increasing risks for food consumers. Moreover, biofilms are difficult to remove and more resistant to antimicrobial agents compared to planktonic cells. Bacteriophages, natural predators of bacteria, can be used as an alternative to prevent biofilm formation or to remove pre-formed biofilm. In this work, four STEC able to produce biofilm were selected among 31 different strains and tested against single bacteriophages and two-phage cocktails. Results showed that our phages were able to reduce biofilm formation by 43.46% both when used as single phage preparation and as a cocktail formulation. Since one of the two cocktails had a slightly better performance, it was used to remove pre-existing biofilms. In this case, the phages were unable to destroy the biofilms and reduce the number of bacterial cells. Our data confirm that preventing biofilm formation in a food plant is better than trying to remove a preformed biofilm and the continuous presence of bacteriophages in the process environment could reduce the number of bacteria able to form biofilms and therefore improve the food safety. Full article
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)
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11 pages, 963 KiB  
Article
Staphylococcus aureus Isolated from the Oral Cavity: Phage Susceptibility in Relation to Antibiotic Resistance
by Katarzyna Garbacz, Ewa Kwapisz, Lidia Piechowicz and Maria Wierzbowska
Antibiotics 2021, 10(11), 1329; https://doi.org/10.3390/antibiotics10111329 - 31 Oct 2021
Cited by 4 | Viewed by 2922
Abstract
Nowadays, research on bacteriophage therapy and its potential use in combination with antibiotics has been gaining momentum. One hundred and ten oral Staphylococcus aureus isolates were phage-typed and their antibiotic resistance was determined by standard and molecular methods. The prevalence of MSSA and [...] Read more.
Nowadays, research on bacteriophage therapy and its potential use in combination with antibiotics has been gaining momentum. One hundred and ten oral Staphylococcus aureus isolates were phage-typed and their antibiotic resistance was determined by standard and molecular methods. The prevalence of MSSA and MRSA strains was 89.1% and 10.9%, respectively. Nearly all (91.8%) analyzed isolates, whether MSSA or MRSA, were susceptible to the phages used from the international set. The highest lytic activity showed phages 79 and 52 A from lytic group I. The predominant phage groups were mixed, the I+III group and a mixed group containing phages from at least three various lytic groups. S. aureus strains sensitive to phage group I were usually resistant to penicillin and susceptible to ciprofloxacin, whereas the strains typeable with group V or group V with the 95 phage were susceptible to most antibiotics. Epidemic CA-MRSA strains (SCCmecIV) of phage type 80/81 carried Panton–Valentine leucocidin genes. Considering the high sensitivity of oral S. aureus to the analyzed phages and the promising results of phage therapies reported by other authors, phage cocktails or phage-antibiotic combinations may potentially find applications in both the prevention and eradication of staphylococcal infections. Full article
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)
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12 pages, 2226 KiB  
Article
Double-Layer Agar (DLA) Modifications for the First Step of the Phage-Antibiotic Synergy (PAS) Identification
by Xymena Stachurska, Marta Roszak, Joanna Jabłońska, Małgorzata Mizielińska and Paweł Nawrotek
Antibiotics 2021, 10(11), 1306; https://doi.org/10.3390/antibiotics10111306 - 26 Oct 2021
Cited by 15 | Viewed by 9245
Abstract
The research carried out so far for phage-antibiotic synergy (PAS) differs as regards the technique of modifying the double-layer agar (DLA) method to show the PAS effect on Petri plates, which may contribute to non-uniform research results. Therefore, there is a need to [...] Read more.
The research carried out so far for phage-antibiotic synergy (PAS) differs as regards the technique of modifying the double-layer agar (DLA) method to show the PAS effect on Petri plates, which may contribute to non-uniform research results. Therefore, there is a need to unify the method to effectively detect the PAS effect, at its most basic in vitro test. In this study, bacteriophage T45 and 43 antibiotics belonging to different antibiotic classes were used. Seven different DLA method modifications were tested, in terms of antibiotic addition placement and presence or absence of the base agar. The overall number of phage plaques per plate mainly depended on the antibiotic used. Differences in plaque quantity depended on the type of the DLA method modification. The largest total number of plaques was obtained by the addition of an antibiotic to a bottom agar with the presence of a top agar. This indicates that even though an antibiotic could manifest the PAS effect by a standard disk method, it would be worth examining if the effect is equally satisfactory when applying antibiotics directly into the agar, with regards to using the same bacteriophage and bacterial host. Full article
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)
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Review

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11 pages, 286 KiB  
Review
Benefits of Combined Phage–Antibiotic Therapy for the Control of Antibiotic-Resistant Bacteria: A Literature Review
by Kevin Diallo and Alain Dublanchet
Antibiotics 2022, 11(7), 839; https://doi.org/10.3390/antibiotics11070839 - 22 Jun 2022
Cited by 27 | Viewed by 3627
Abstract
With the increase in bacterial resistance to antibiotics, more and more therapeutic failures are being reported worldwide. The market for antibiotics is now broken due to the high cost of developing new molecules. A promising solution to bacterial resistance is combined phage–antibiotic therapy, [...] Read more.
With the increase in bacterial resistance to antibiotics, more and more therapeutic failures are being reported worldwide. The market for antibiotics is now broken due to the high cost of developing new molecules. A promising solution to bacterial resistance is combined phage–antibiotic therapy, a century-old method that can potentiate existing antibiotics by prolonging or even restoring their activity against specific bacteria. The aim of this literature review was to provide an overview of different phage–antibiotic combinations and to describe the possible mechanisms of phage–antibiotic synergy. Full article
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)
18 pages, 3437 KiB  
Review
Molecular Modeling the Proteins from the exo-xis Region of Lambda and Shigatoxigenic Bacteriophages
by Logan W. Donaldson
Antibiotics 2021, 10(11), 1282; https://doi.org/10.3390/antibiotics10111282 - 21 Oct 2021
Cited by 3 | Viewed by 2446
Abstract
Despite decades of intensive research on bacteriophage lambda, a relatively uncharacterized region remains between the exo and xis genes. Collectively, exo-xis region genes are expressed during the earliest stages of the lytic developmental cycle and are capable of affecting the molecular events associated [...] Read more.
Despite decades of intensive research on bacteriophage lambda, a relatively uncharacterized region remains between the exo and xis genes. Collectively, exo-xis region genes are expressed during the earliest stages of the lytic developmental cycle and are capable of affecting the molecular events associated with the lysogenic-lytic developmental decision. In Shiga toxin-producing E. coli (STEC) and enterohemorragic E. coli (EHEC) that are responsible for food- and water-borne outbreaks throughout the world, there are distinct differences of exo-xis region genes from their counterparts in lambda phage. Together, these differences may help EHEC-specific phage and their bacterial hosts adapt to the complex environment within the human intestine. Only one exo-xis region protein, Ea8.5, has been solved to date. Here, I have used the AlphaFold and RoseTTAFold machine learning algorithms to predict the structures of six exo-xis region proteins from lambda and STEC/EHEC phages. Together, the models suggest possible roles for exo-xis region proteins in transcription and the regulation of RNA polymerase. Full article
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)
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13 pages, 944 KiB  
Review
Bacteriophage Technology and Modern Medicine
by Aa Haeruman Azam, Xin-Ee Tan, Srivani Veeranarayanan, Kotaro Kiga and Longzhu Cui
Antibiotics 2021, 10(8), 999; https://doi.org/10.3390/antibiotics10080999 - 18 Aug 2021
Cited by 19 | Viewed by 8650
Abstract
The bacteriophage (or phage for short) has been used as an antibacterial agent for over a century but was abandoned in most countries after the discovery and broad use of antibiotics. The worldwide emergence and high prevalence of antimicrobial-resistant (AMR) bacteria have led [...] Read more.
The bacteriophage (or phage for short) has been used as an antibacterial agent for over a century but was abandoned in most countries after the discovery and broad use of antibiotics. The worldwide emergence and high prevalence of antimicrobial-resistant (AMR) bacteria have led to a revival of interest in the long-forgotten antibacterial therapy with phages (phage therapy) as an alternative approach to combatting AMR bacteria. The rapid progress recently made in molecular biology and genetic engineering has accelerated the generation of phage-related products with superior therapeutic potentials against bacterial infection. Nowadays, phage-based technology has been developed for many purposes, including those beyond the framework of antibacterial treatment, such as to suppress viruses by phages, gene therapy, vaccine development, etc. Here, we highlighted the current progress in phage engineering technology and its application in modern medicine. Full article
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)
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