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Antibiotics
Special Issues
Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections
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Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections

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

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 43128

Special Issue Editors

Dr. Bożena Nejman-Faleńczyk

E-Mail Website
Guest Editor
Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland
Interests: small noncoding RNAs; bacteriophage functional genomics; STEC bacteria
Dr. Sylwia Bloch

E-Mail Website
Guest Editor
Laboratory of Phage Therapy, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Gdańsk, Poland
Interests: bacteriophages; phage therapy; EHEC; Shiga toxins; small non-coding RNAs; gene expression

Special Issue Information

Dear Colleagues,

The rapid dissemination of antibiotic-resistant bacteria is occurring worldwide and generates serious medical problems. In the light of this, the search for new, alternative solutions is extremely important. Phage-based strategies seem to be very promising. Therefore, the aim of this Special Issue is to focus on the possibilities for use of whole bacteriophages as well as phage-based agents, e.g., bacteriolysins, antimicrobial peptides (AMPs) or other products of phage origin, to fight against pathogenic bacteria. Among these agents, particular attention will be paid to phage lytic enzymes and their engineered derivatives that are currently the subject of important discussion. In addition, considerations for combined therapies will also be desirable. Please note that we are interested in phage-based approaches that control bacterial infections in different areas, not only medicine. Examples from the agriculture, industry, natural environments, etc. will also be appreciated. Below is a list of the main thematic categories. If needed, related but not completely matching manuscripts will also be considered for publication.

  1. Phage-encoded bacteriolysins and their engineered derivatives;
  2. Antimicrobial peptides or other agents of phage origin to treat bacterial infections;
  3. Phage therapy;
  4. Phage-display as a strategy to generate and deliver antimicrobial agents;
  5. Bacteriophage functional genomics for therapeutic solutions;
  6. Characteristics and applications of new phages;
  7. Bacterial resistance to phages and antibiotics;
  8. Bacteriophages, phage-based agents, and antibiotics in combination treatment.

Dr. Bożena Nejman-Faleńczyk
Dr. Sylwia Bloch
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 submissions that pass pre-check are 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 2900 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

  • bacteriophages
  • bacteriolysins
  • antimicrobial peptides
  • phage therapy
  • antibacterial strategies

Published Papers (7 papers)

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Research

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19 pages, 4226 KiB  
Article
Antibacterial, Antifungal and Anticancer Activities of Compounds Produced by Newly Isolated Streptomyces Strains from the Szczelina Chochołowska Cave (Tatra Mountains, Poland)
by Weronika Jaroszewicz, Patrycja Bielańska, Daria Lubomska, Katarzyna Kosznik-Kwaśnicka, Piotr Golec, Łukasz Grabowski, Ewa Wieczerzak, Weronika Dróżdż, Lidia Gaffke, Karolina Pierzynowska, Grzegorz Węgrzyn and Alicja Węgrzyn
Antibiotics 2021, 10(10), 1212; https://doi.org/10.3390/antibiotics10101212 - 05 Oct 2021
Cited by 18 | Viewed by 3254
Abstract
Resistance of bacteria, fungi and cancer cells to antibiotics and other drugs is recognized as one of the major problems in current medicine. Therefore, a search for new biologically active compounds able to either kill pathogenic cells or inhibit their growth is mandatory. [...] Read more.
Resistance of bacteria, fungi and cancer cells to antibiotics and other drugs is recognized as one of the major problems in current medicine. Therefore, a search for new biologically active compounds able to either kill pathogenic cells or inhibit their growth is mandatory. Hard-to-reach habitats appear to be unexplored sources of microorganisms producing previously unknown antibiotics and other molecules revealing potentially therapeutic properties. Caves belong to such habitats, and Actinobacteria are a predominant group of microorganisms occurring there. This group of bacteria are known for production of many antibiotics and other bioactive compounds. Interestingly, it was demonstrated previously that infection with bacteriophages might enhance production of antibiotics by them. Here, we describe a series of newly isolated strains of Actinobacteria that were found in caves from the Tatra Mountains (Poland). Phage induction tests indicated that some of them may bear active prophages able to produce virions upon treatment with mitomycin C or UV irradiation. Among all the examined bacteria, two newly isolated Streptomyces sp. strains were further characterized to demonstrate their ability to inhibit the growth of pathogenic bacteria (strains of Staphylococcus aureus, Salmonella enterica, Enterococcus sp., Escherichia coli, and Pseudomonas aeruginosa) and fungi (different species and strains from the genus Candida). Moreover, extracts from these Streptomyces strains reduced viability of the breast-cancer cell line T47D. Chemical analyses of these extracts indicated the presence of isomers of dichloranthrabenzoxocinone and 4,10- or 10,12-dichloro-3-O-methylanthrabenzoxocinone, which are putative antimicrobial compounds. Moreover, various previously unknown (unclassified) molecules were also detected using liquid chromatography–mass spectrometry, suggesting that tested Streptomyces strains may synthesize a battery of bioactive compounds with antibacterial, antifungal, and anticancer activities. These results indicate that further studies on the newly isolated Actinobacteria might be a promising approach to develop novel antibacterial, antifungal, and/or anticancer drugs. Full article
(This article belongs to the Special Issue Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections)
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14 pages, 2553 KiB  
Article
Bacteriophage SRD2021 Recognizing Capsular Polysaccharide Shows Therapeutic Potential in Serotype K47 Klebsiella pneumoniae Infections
by Guijuan Hao, Rundong Shu, Liqin Ding, Xia Chen, Yonghao Miao, Jiaqi Wu, Haijian Zhou and Hui Wang
Antibiotics 2021, 10(8), 894; https://doi.org/10.3390/antibiotics10080894 - 22 Jul 2021
Cited by 13 | Viewed by 2585
Abstract
Klebsiella pneumoniae is an opportunistic pathogen posing an urgent threat to global public health, and the capsule is necessary for K. pneumoniae infection and virulence. Phage-derived capsule depolymerases have shown great potential as antivirulence agents in treating carbapenem-resistant K. pneumoniae (CRKP) infections. However, [...] Read more.
Klebsiella pneumoniae is an opportunistic pathogen posing an urgent threat to global public health, and the capsule is necessary for K. pneumoniae infection and virulence. Phage-derived capsule depolymerases have shown great potential as antivirulence agents in treating carbapenem-resistant K. pneumoniae (CRKP) infections. However, the therapeutic potential of phages encoding depolymerases against CRKP remains poorly understood. In this study, we identified a long-tailed phage SRD2021 specific for mucoid CRKP with capsular K47 serotype, which is the predominant infectious K-type in Asia. Genome sequencing revealed that ΦSRD2021 belonged to the Drulisvirus genus and exhibited a capsular depolymerase domain in its tail fiber protein. A transposon-insertion library of host bacteria was constructed to identify the receptor for ΦSRD2021. We found that most phage-resistant mutants converted to a nonmucoid phenotype, including the mutant in wza gene essential for capsular polysaccharides export. Further knockout and complementation experiments confirmed that the Δwza mutant avoided adsorption by ΦSRD2021, indicating that the K47 capsular polysaccharide is the necessary receptor for phage infection. ΦSRD2021 lysed the bacteria mature biofilms and showed a therapeutic effect on the prevention and treatment of CRKP infection in the Galleria mellonella model. Furthermore, ΦSRD2021 also reduced the colonized CRKP in mouse intestines significantly. By recognizing the host capsule as a receptor, our results showed that ΦSRD2021 may be used as a potential antibacterial agent for K47 serotype K. pneumoniae infections. Full article
(This article belongs to the Special Issue Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections)
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Review

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36 pages, 3978 KiB  
Review
Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application
by Katarzyna M. Danis-Wlodarczyk, Daniel J. Wozniak and Stephen T. Abedon
Antibiotics 2021, 10(12), 1497; https://doi.org/10.3390/antibiotics10121497 - 06 Dec 2021
Cited by 39 | Viewed by 9932
Abstract
Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes [...] Read more.
Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes in development pipelines. Innovative antibacterial therapeutics and strategies are, therefore, in grave need. For the last twenty years, antimicrobial enzymes encoded by bacteriophages, viruses that can lyse and kill bacteria, have gained tremendous interest. There are two classes of these phage-derived enzymes, referred to also as enzybiotics: peptidoglycan hydrolases (lysins), which degrade the bacterial peptidoglycan layer, and polysaccharide depolymerases, which target extracellular or surface polysaccharides, i.e., bacterial capsules, slime layers, biofilm matrix, or lipopolysaccharides. Their features include distinctive modes of action, high efficiency, pathogen specificity, diversity in structure and activity, low possibility of bacterial resistance development, and no observed cross-resistance with currently used antibiotics. Additionally, and unlike antibiotics, enzybiotics can target metabolically inactive persister cells. These phage-derived enzymes have been tested in various animal models to combat both Gram-positive and Gram-negative bacteria, and in recent years peptidoglycan hydrolases have entered clinical trials. Here, we review the testing and clinical use of these enzymes. Full article
(This article belongs to the Special Issue Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections)
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13 pages, 1035 KiB  
Review
The Potential Role of Bacteriophages in the Treatment of Recalcitrant Chronic Rhinosinusitis
by Saartje Uyttebroek, Jolien Onsea, Willem-Jan Metsemakers, Lieven Dupont, David Devolder, Jeroen Wagemans, Rob Lavigne, Isabel Spriet and Laura Van Gerven
Antibiotics 2021, 10(6), 675; https://doi.org/10.3390/antibiotics10060675 - 05 Jun 2021
Cited by 7 | Viewed by 6478
Abstract
Chronic rhinosinusitis is a common condition affecting 5–12% of the general population worldwide. In a limited number of cases, the disease is recalcitrant to medical and surgical interventions, causing a major impact on physical, social and emotional well-being and increasing pressure on healthcare [...] Read more.
Chronic rhinosinusitis is a common condition affecting 5–12% of the general population worldwide. In a limited number of cases, the disease is recalcitrant to medical and surgical interventions, causing a major impact on physical, social and emotional well-being and increasing pressure on healthcare systems. Biofilm formation and dysbiosis caused by Staphylococcus aureus and Pseudomonas aeruginosa play a role in the pathogenesis of recalcitrant chronic rhinosinusitis. In these cases, a promising treatment alternative is the application of bacteriophages, which are viruses that infect and lyse bacteria. In this review, we appraise the evidence for the use of bacteriophages in the treatment of recalcitrant chronic rhinosinusitis. Additionally, (dis)advantages of bacteriophages and considerations for implementation of phage therapy in otorhinolaryngology practice will be discussed. Full article
(This article belongs to the Special Issue Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections)
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21 pages, 1459 KiB  
Review
Bacteriophage-Derived Depolymerases against Bacterial Biofilm
by Gracja Topka-Bielecka, Aleksandra Dydecka, Agnieszka Necel, Sylwia Bloch, Bożena Nejman-Faleńczyk, Grzegorz Węgrzyn and Alicja Węgrzyn
Antibiotics 2021, 10(2), 175; https://doi.org/10.3390/antibiotics10020175 - 10 Feb 2021
Cited by 44 | Viewed by 6999
Abstract
In addition to specific antibiotic resistance, the formation of bacterial biofilm causes another level of complications in attempts to eradicate pathogenic or harmful bacteria, including difficult penetration of drugs through biofilm structures to bacterial cells, impairment of immunological response of the host, and [...] Read more.
In addition to specific antibiotic resistance, the formation of bacterial biofilm causes another level of complications in attempts to eradicate pathogenic or harmful bacteria, including difficult penetration of drugs through biofilm structures to bacterial cells, impairment of immunological response of the host, and accumulation of various bioactive compounds (enzymes and others) affecting host physiology and changing local pH values, which further influence various biological functions. In this review article, we provide an overview on the formation of bacterial biofilm and its properties, and then we focus on the possible use of phage-derived depolymerases to combat bacterial cells included in this complex structure. On the basis of the literature review, we conclude that, although these bacteriophage-encoded enzymes may be effective in destroying specific compounds involved in the formation of biofilm, they are rarely sufficient to eradicate all bacterial cells. Nevertheless, a combined therapy, employing depolymerases together with antibiotics and/or other antibacterial agents or factors, may provide an effective approach to treat infections caused by bacteria able to form biofilms. Full article
(This article belongs to the Special Issue Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections)
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17 pages, 351 KiB  
Review
Growing Trend of Fighting Infections in Aquaculture Environment—Opportunities and Challenges of Phage Therapy
by Justyna D. Kowalska, Joanna Kazimierczak, Patrycja M. Sowińska, Ewelina A. Wójcik, Andrzej K. Siwicki and Jarosław Dastych
Antibiotics 2020, 9(6), 301; https://doi.org/10.3390/antibiotics9060301 - 04 Jun 2020
Cited by 32 | Viewed by 6004
Abstract
Phage therapy, a promising alternative to antimicrobial treatment of bacterial diseases, is getting more and more popular, especially due to the rising awareness of antibiotic resistance and restrictions in antibiotics’ use. During recent years, we observed a growing trend of bacteriophages’ application in [...] Read more.
Phage therapy, a promising alternative to antimicrobial treatment of bacterial diseases, is getting more and more popular, especially due to the rising awareness of antibiotic resistance and restrictions in antibiotics’ use. During recent years, we observed a growing trend of bacteriophages’ application in aquaculture, which in each year reports high losses due to bacterial diseases. This review provides an update of the status of bacteriophage therapy for the treatment and prevention of infections in the aquatic environment. As it is still mostly in the scientific stage, there are a few constraints that may prevent effective therapy. Therefore, specific characteristics of bacteriophages, that can act in favor or against their successful use in treatment, were described. We underlined aspects that need to be considered: specificity of phages, bacterial resistance, safety, immune response of the host organism, formulation, administration and stability of phage preparations as well as bacteriophages’ influence on the environment. The biggest challenge to overcome is finding the right balance between the desired and problematic characteristics of bacteriophages. Finally, regulatory approval challenges may be encountered by bacteriophage manufacturers. Even though there are still some technical constraints connected with the global use of bacteriophage therapy, it was concluded that it can be successfully applied in aquaculture. Full article
(This article belongs to the Special Issue Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections)

Other

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7 pages, 216 KiB  
Perspective
Phage Therapy: Towards a Successful Clinical Trial
by Andrzej Górski, Jan Borysowski and Ryszard Międzybrodzki
Antibiotics 2020, 9(11), 827; https://doi.org/10.3390/antibiotics9110827 - 19 Nov 2020
Cited by 62 | Viewed by 6097
Abstract
While phage therapy carried out as compassionate use (experimental therapy) has recently flourished, providing numerous case reports of supposedly healed patients, clinical trials aiming to formally prove their value in accord with current regulatory requirements have failed. In light of the current issue [...] Read more.
While phage therapy carried out as compassionate use (experimental therapy) has recently flourished, providing numerous case reports of supposedly healed patients, clinical trials aiming to formally prove their value in accord with current regulatory requirements have failed. In light of the current issue of increasing antibiotic resistance, the need for a final say regarding the place of phage therapy in modern medicine is evident. We analyze the possible factors that may favor success or lead to the failure of phage therapy: quality of phage preparations, their titer and dosage, as well as external factors that could also contribute to the outcome of phage therapy. Hopefully, better control of these factors may eventually bring about long-awaited positive results. Full article
(This article belongs to the Special Issue Bacteriolysins and Other Phage-Based Strategies to Combat Bacterial Infections)
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