Special Issue "Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come"

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 July 2020).

Special Issue Editors

Prof. Dr. Tomás González Villa
E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Pharmacy, University of Santiago de Compostela, 15706 Santiago de Compostela, Coruna, Spain
Interests: phage therapy; microbiology; microbial biotechnology; food microbiology; molecular microbiology; recombinant microorganisms; microbial bioactive compounds
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Carmen Sieiro
E-Mail Website
Guest Editor
Department of Functional Biology and Health Sciences, Microbiology Unit, University of Vigo, Lagoas-Marcosende, 36310 Vigo, Spain
Interests: microbiology; microbial biotechnology; food microbiology; recombinant microorganisms; microbial enzymes; microbial bioactive compounds; antimicrobials; biopreservatives; biocontrol; bacteriophages; probiotics

Special Issue Information

Dear Colleagues,

Conventional antimicrobials have been for decades the panacea for controlling pathogenic and non-desirable bacteria, ever since the introduction of the “magic-bullet” idea by Paul Ehrlich at the beginning of the XXth century. The prescription, the missuse and most importantly the genesis of several spontaneous mutants has led to the emergence of multiresistant bacteria to antibiotics, commonly used in the treatment of current and deadly forms of diseases both in humans and other animals, to such an extent that practitioners often run out of effective prescriptions. Combination of therapies or treatments, based on different compounds is generally recognized as the more effective strategy to fight resistances. Bacteriophages (phages) are viruses that kill bacteria in a quite specific manner. Proposed a century ago, and then forgotten in western countries, phages and their lysins have emerged recently in the West as promising alternative against pathogenic bacteria, and have to walk together with the current chemotherapy including antibiotics, to design new combined strategies for the control of non-desirable bacteria, particularly those exhibiting multiresistant phenotypes.

This special issue of "Phage therapy, lysin therapy, and antibiotics, a trio due to come" deals with the more recent advances in these combined therapies. The issue welcomes various submission types, such as original research papers, short communications, reviews, case reports, and perspectives.

  • Potential topics for this special issue include, but are not limited to:
  • Search for phages and lysins with new mechanisms of action
  • Advanced phage and lysins therapies or combined therapies with antibiotics in clinics and veterinary, including aquaculture (particularly in intensive cultures)
  • Phage and lysin treatments for food-biopreservation
  • Phage and lysin treatments against phytopathogenic bacteria
  • Phage treatment of drinking water reservoirs
  • Phage treatment of sewage waters
  • Environment control of multidrug resistant bacteria: reversion of multidrug resistances
  • Tailor-made phages and lysins designed for specific purposes: new genetically modified phages and lysins
  • Precise formulation of phages for a variety of uses on/off clinics
  • Prevention of resistances to phages and lysins

Prof. Dr. Tomas. G. Villa
Prof. Carmen Sieiro
Guest Editors

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. Antibiotics 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 and lysin therapies
  • phage lysins
  • lytic bacteriophages
  • lysogenic bacteriophages
  • recombinant bacteriophages
  • recombinant lysins
  • mutated bacteriophages
  • bacterial diseases
  • bacteriophage-assisted antibiotherapy
  • combined therapies

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

Editorial
Phage Therapy, Lysin Therapy, and Antibiotics: A Trio Due to Come
Antibiotics 2020, 9(9), 604; https://doi.org/10.3390/antibiotics9090604 - 15 Sep 2020
Cited by 2 | Viewed by 794
Abstract
Since their introduction, at the beginning of the 20th century, antibiotics were regarded as “magic-bullets”, a term coined by Paul Ehrlich, and, for several decades, considered as the universal panacea to combat pathogenic and/or undesirable bacteria [...] Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)

Research

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Article
Bacteriophage-Induced Lipopolysaccharide Mutations in Escherichia coli Lead to Hypersensitivity to Food Grade Surfactant Sodium Dodecyl Sulfate
Antibiotics 2020, 9(9), 552; https://doi.org/10.3390/antibiotics9090552 - 28 Aug 2020
Cited by 1 | Viewed by 1080
Abstract
Bacteriophages (phages) are considered as one of the most promising antibiotic alternatives in combatting bacterial infectious diseases. However, one concern of employing phage application is the emergence of bacteriophage-insensitive mutants (BIMs). Here, we isolated six BIMs from E. coli B in the presence [...] Read more.
Bacteriophages (phages) are considered as one of the most promising antibiotic alternatives in combatting bacterial infectious diseases. However, one concern of employing phage application is the emergence of bacteriophage-insensitive mutants (BIMs). Here, we isolated six BIMs from E. coli B in the presence of phage T4 and characterized them using genomic and phenotypic methods. Of all six BIMs, a six-amino acid deletion in glucosyltransferase WaaG likely conferred phage resistance by deactivating the addition of T4 receptor glucose to the lipopolysaccharide (LPS). This finding was further supported by the impaired phage adsorption to BIMs and glycosyl composition analysis which quantitatively confirmed the absence of glucose in the LPS of BIMs. Since LPSs actively maintain outer membrane (OM) permeability, phage-induced truncations of LPSs destabilized the OM and sensitized BIMs to various substrates, especially to the food-grade surfactant sodium dodecyl sulfate (SDS). This hypersensitivity to SDS was exploited to design a T4–SDS combination which successfully prevented the generation of BIMs and eliminated the inoculated bacteria. Collectively, phage-driven modifications of LPSs immunized BIMs from T4 predation but increased their susceptibilities as a fitness cost. The findings of this study suggest a novel strategy to enhance the effectiveness of phage-based food safety interventions. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Article
Enzybiotics LYSSTAPH-S and LYSDERM-S as Potential Therapeutic Agents for Chronic MRSA Wound Infections
Antibiotics 2020, 9(8), 519; https://doi.org/10.3390/antibiotics9080519 - 15 Aug 2020
Cited by 1 | Viewed by 1282
Abstract
Antibacterial antibiotic therapy has played an important role in the treatment of bacterial infections for almost a century. The increasing resistance of pathogenic bacteria to antibiotics leads to an attempt to use previously neglected antibacterial therapies. Here we provide information on the two [...] Read more.
Antibacterial antibiotic therapy has played an important role in the treatment of bacterial infections for almost a century. The increasing resistance of pathogenic bacteria to antibiotics leads to an attempt to use previously neglected antibacterial therapies. Here we provide information on the two recombinantly modified antistaphylococcal enzymes derived from lysostaphin (LYSSTAPH-S) and endolysin (LYSDERM-S) derived from kayvirus 812F1 whose target sites reside in the bacterial cell wall. LYSSTAPH-S showed a stable antimicrobial effect over 24-h testing, even in concentrations lower than 1 µg/mL across a wide variety of epidemiologically important sequence types (STs) of methicillin-resistant Staphylococcus aureus (MRSA), especially in the stationary phase of growth (status comparable to chronic infections). LYSDERM-S showed a less potent antimicrobial effect that lasted only a few hours at concentrations of 15 μg/mL and higher. Our data indicate that these antimicrobial enzymes could be of substantial help in the treatment of chronic MRSA wound infections. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Article
Characterization of Clinical MRSA Isolates from Northern Spain and Assessment of Their Susceptibility to Phage-Derived Antimicrobials
Antibiotics 2020, 9(8), 447; https://doi.org/10.3390/antibiotics9080447 - 25 Jul 2020
Cited by 5 | Viewed by 1284
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent nosocomial pathogen, causing a wide range of diseases. The increased frequency of MRSA isolates in hospitals and the emergence of vancomycin resistance have sparked the search for new control strategies. This study aimed to characterize sixty-seven [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent nosocomial pathogen, causing a wide range of diseases. The increased frequency of MRSA isolates in hospitals and the emergence of vancomycin resistance have sparked the search for new control strategies. This study aimed to characterize sixty-seven MRSA isolates collected from both infected patients and asymptomatic carriers in a Spanish hospital. RAPD-PCR allowed the identification of six genetic patterns. We also investigated the presence of genes involved in producing adhesins, toxins and the capsule; the biofilm; and antimicrobial resistance. A notable percentage of the isolates carried virulence genes and showed medium-high ability to form biofilms. Next, we assessed the strains’ susceptibility to two phages (phiIPLA-C1C and phiIPLA-RODI) and one endolysin (LysRODI). All strains were resistant to phiIPLA-C1C, and most (70.2%) were susceptible to phiIPLA-RODI. Regarding LysRODI, all strains displayed susceptibility, although to varying degrees. There was a correlation between endolysin susceptibility and the random amplification of polymorphic DNA (RAPD) profile or the presence of some virulence genes (fnbA, eta, etb, PVL and czr), but that was not observed with biofilm-forming ability, strain origin or phage sensitivity. Taken together, these findings can help to explain the factors influencing endolysin effectiveness, which will contribute to the development of efficient therapies targeting MRSA infections. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Article
Proteomic Characterization of Antibiotic Resistance, and Production of Antimicrobial and Virulence Factors in Streptococcus Species Associated with Bovine Mastitis. Could Enzybiotics Represent Novel Therapeutic Agents Against These Pathogens?
Antibiotics 2020, 9(6), 302; https://doi.org/10.3390/antibiotics9060302 - 04 Jun 2020
Cited by 5 | Viewed by 1717
Abstract
Streptococcus spp. are major mastitis pathogens present in dairy products, which produce a variety of virulence factors that are involved in streptococcal pathogenicity. These include neuraminidase, pyrogenic exotoxin, and M protein, and in addition they might produce bacteriocins and antibiotic-resistance proteins. Unjustifiable misuse [...] Read more.
Streptococcus spp. are major mastitis pathogens present in dairy products, which produce a variety of virulence factors that are involved in streptococcal pathogenicity. These include neuraminidase, pyrogenic exotoxin, and M protein, and in addition they might produce bacteriocins and antibiotic-resistance proteins. Unjustifiable misuse of antimicrobials has led to an increase in antibiotic-resistant bacteria present in foodstuffs. Identification of the mastitis-causing bacterial strain, as well as determining its antibiotic resistance and sensitivity is crucial for effective therapy. The present work focused on the LC–ESI–MS/MS (liquid chromatography–electrospray ionization tandem mass spectrometry) analysis of tryptic digestion peptides from mastitis-causing Streptococcus spp. isolated from milk. A total of 2706 non-redundant peptides belonging to 2510 proteins was identified and analyzed. Among them, 168 peptides were determined, representing proteins that act as virulence factors, toxins, anti-toxins, provide resistance to antibiotics that are associated with the production of lantibiotic-related compounds, or play a role in the resistance to toxic substances. Protein comparisons with the NCBI database allowed the identification of 134 peptides as specific to Streptococcus spp., while two peptides (EATGNQNISPNLTISNAQLNLEDKNK and DLWC*NM*IIAAK) were found to be species-specific to Streptococcus dysgalactiae. This proteomic repository might be useful for further studies and research work, as well as for the development of new therapeutics for the mastitis-causing Streptococcus strains. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Review

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Review
A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives
Antibiotics 2020, 9(9), 580; https://doi.org/10.3390/antibiotics9090580 - 06 Sep 2020
Cited by 2 | Viewed by 1666
Abstract
Cancer is predominantly considered as an environmental disease caused by genetic or epigenetic alterations induced by exposure to extrinsic (e.g., carcinogens, pollutants, radiation) or intrinsic (e.g., metabolic, immune or genetic deficiencies). Over-exposure to antibiotics, which is favored by unregulated access as well as [...] Read more.
Cancer is predominantly considered as an environmental disease caused by genetic or epigenetic alterations induced by exposure to extrinsic (e.g., carcinogens, pollutants, radiation) or intrinsic (e.g., metabolic, immune or genetic deficiencies). Over-exposure to antibiotics, which is favored by unregulated access as well as inappropriate prescriptions by physicians, is known to have led to serious health problems such as the rise of antibiotic resistance, in particular in poorly developed countries. In this review, the attention is focused on evaluating the effects of antibiotic exposure on cancer risk and on the outcome of cancer therapeutic protocols, either directly acting as extrinsic promoters, or indirectly, through interactions with the human gut microbiota. The preponderant evidence derived from information reported over the last 10 years confirms that antibiotic exposure tends to increase cancer risk and, unfortunately, that it reduces the efficacy of various forms of cancer therapy (e.g., chemo-, radio-, and immunotherapy alone or in combination). Alternatives to the current patterns of antibiotic use, such as introducing new antibiotics, bacteriophages or enzybiotics, and implementing dysbiosis-reducing microbiota modulatory strategies in oncology, are discussed. The information is in the end considered from the perspective of the most recent findings on the tumor-specific and intracellular location of the tumor microbiota, and of the most recent theories proposed to explain cancer etiology on the notion of regression of the eukaryotic cells and systems to stages characterized for a lack of coordination among their components of prokaryotic origin, which is promoted by injuries caused by environmental insults. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Review
Recycling Old Antibiotics with Ionic Liquids
Antibiotics 2020, 9(9), 578; https://doi.org/10.3390/antibiotics9090578 - 04 Sep 2020
Cited by 7 | Viewed by 1473
Abstract
Antibiotics are considered one of the great “miracles” of the 20th century. Now in the 21st century in the post-antibiotic era, the miracle is turning into a nightmare, due to the growing problem of the resistance of microorganisms to classic antimicrobials and the [...] Read more.
Antibiotics are considered one of the great “miracles” of the 20th century. Now in the 21st century in the post-antibiotic era, the miracle is turning into a nightmare, due to the growing problem of the resistance of microorganisms to classic antimicrobials and the non-investment by the pharmaceutical industry in new antimicrobial agents. Unfortunately, the current COVID-19 pandemic has demonstrated the global risks associated with uncontrolled infections and the various forms of impact that such a pandemic may have on the economy and on social habits besides the associated morbidity and mortality. Therefore, there is an urgent need to recycle classic antibiotics, as is the case in the use of ionic liquids (ILs) based on antibiotics. Thus, the aim of the present review is to summarize the data on ILs, mainly those with antimicrobial action and especially against resistant strains. The main conclusions of this article are that ILs are flexible due to their ability to modulate cations and anions as a salt, making it possible to combine the properties of both and multiplying the activity of separate cations and anions. Also, these compounds have low cost methods of production, which makes it highly attractive to explore them, especially as antimicrobial agents and against resistant strains. ILs may further be combined with other therapeutic strategies, such as phage or lysine therapy, enhancing the therapeutic arsenal needed to fight this worldwide problem of antibacterial resistance. Thus, the use of ILs as antibiotics by themselves or together with phage therapy and lysine therapy are promising alternatives against pathogenic microorganisms, and may have the possibility to be used in new ways in order to restrain uncontrolled infections. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Review
A Hundred Years of Bacteriophages: Can Phages Replace Antibiotics in Agriculture and Aquaculture?
Antibiotics 2020, 9(8), 493; https://doi.org/10.3390/antibiotics9080493 - 07 Aug 2020
Cited by 13 | Viewed by 2594
Abstract
Agriculture, together with aquaculture, supplies most of the foodstuffs required by the world human population to survive. Hence, bacterial diseases affecting either agricultural crops, fish, or shellfish not only cause large economic losses to producers but can even create food shortages, resulting in [...] Read more.
Agriculture, together with aquaculture, supplies most of the foodstuffs required by the world human population to survive. Hence, bacterial diseases affecting either agricultural crops, fish, or shellfish not only cause large economic losses to producers but can even create food shortages, resulting in malnutrition, or even famine, in vulnerable populations. Years of antibiotic use in the prevention and the treatment of these infections have greatly contributed to the emergence and the proliferation of multidrug-resistant bacteria. This review addresses the urgent need for alternative strategies for the use of antibiotics, focusing on the use of bacteriophages (phages) as biocontrol agents. Phages are viruses that specifically infect bacteria; they are highly host-specific and represent an environmentally-friendly alternative to antibiotics to control and kill pathogenic bacteria. The information evaluated here highlights the effectiveness of phages in the control of numerous major pathogens that affect both agriculture and aquaculture, with special emphasis on scientific and technological aspects still requiring further development to establish phagotherapy as a real universal alternative to antibiotic treatment. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Review
Bacteriophages and Lysins as Possible Alternatives to Treat Antibiotic-Resistant Urinary Tract Infections
Antibiotics 2020, 9(8), 466; https://doi.org/10.3390/antibiotics9080466 - 30 Jul 2020
Cited by 10 | Viewed by 1830
Abstract
Urinary tract infections represent a major public health problem as the rapid emergence of antibiotic-resistant strains among uropathogens is causing the failure of many current treatments. The use of bacteriophages (phages) and their derivatives to combat infectious diseases is an old approach that [...] Read more.
Urinary tract infections represent a major public health problem as the rapid emergence of antibiotic-resistant strains among uropathogens is causing the failure of many current treatments. The use of bacteriophages (phages) and their derivatives to combat infectious diseases is an old approach that has been forgotten by the West for a long time, mostly due to the discovery and great success of antibiotics. In the present so-called “post-antibiotic era”, many researchers are turning their attention to the re-discovered phage therapy, as an effective alternative to antibiotics. Phage therapy includes the use of natural or engineered phages, as well as their purified lytic enzymes to destroy pathogenic strains. Many in vitro and in vivo studies have been conducted, and these have proved the great potential for this therapy against uropathogenic bacteria. Nevertheless, to date, the lack of appropriate clinical trials has hindered its widespread clinic application. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Review
Phages for Biofilm Removal
Antibiotics 2020, 9(5), 268; https://doi.org/10.3390/antibiotics9050268 - 21 May 2020
Cited by 30 | Viewed by 3030
Abstract
Biofilms are clusters of bacteria that live in association with surfaces. Their main characteristic is that the bacteria inside the biofilms are attached to other bacterial cells and to the surface by an extracellular polymeric matrix. Biofilms are capable of adhering to a [...] Read more.
Biofilms are clusters of bacteria that live in association with surfaces. Their main characteristic is that the bacteria inside the biofilms are attached to other bacterial cells and to the surface by an extracellular polymeric matrix. Biofilms are capable of adhering to a wide variety of surfaces, both biotic and abiotic, including human tissues, medical devices, and other materials. On these surfaces, biofilms represent a major threat causing infectious diseases and economic losses. In addition, current antibiotics and common disinfectants have shown limited ability to remove biofilms adequately, and phage-based treatments are proposed as promising alternatives for biofilm eradication. This review analyzes the main advantages and challenges that phages can offer for the elimination of biofilms, as well as the most important factors to be taken into account in order to design effective phage-based treatments. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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