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Antibiotics
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Bacteriophages: An Inspiration for the Development of New Antimicrobial and...
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Bacteriophages: An Inspiration for the Development of New Antimicrobial and Antibiofilm Agents

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

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 19663

Special Issue Editor

Dr. Lucía Fernández

E-Mail Website
Guest Editor
Department of Technology and Biotechnology of Dairy Products, Dairy Research Institute of Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain
Interests: phage-derived antimicrobials; anti-biofilm strategies; antibiotic resistance; Staphylococcus aureus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the context of the current antimicrobial resistance crisis, the development of novel and revamped strategies to fight pathogenic bacteria is paramount. A good example of this is the relatively recent revival of phage therapy. Once discarded as flawed compared to antibiotics, the use of bacterial viruses as sophisticated, high precision weapons is again considered a viable option. Beyond that, bacteriophages also serve as inspiration for the design of new antimicrobial compounds. For instance, phage-derived lytic proteins, also called enzybiotics, can be per se very effective in killing undesired bacteria, while hardly selecting any resistant mutants. Another good example is the application of phage depolymerases to degrade the capsule surrounding bacterial cells and the exopolysaccharides present in the biofilm matrix. Nonetheless, the use of phages or their proteins for biocidal and therapeutic purposes is still shrouded in controversy and further tests are required to attain full regulatory approval. This special issue aims to provide an update on phage-based antimicrobials, including, but not limited to, their efficacy and safety, the design of new protocols to ensure therapeutic success, their combination with other antibacterial agents, their use against bacterial biofilms, and the potential development of bacterial resistance.

Dr. Lucía Fernández
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 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

  • phage therapy
  • phage lytic proteins
  • phage depolymerases: novel antimicrobials
  • antibiofilm agents

Published Papers (5 papers)

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Research

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14 pages, 2646 KiB  
Communication
Characterization of the Bacteriophage-Derived Endolysins PlySs2 and PlySs9 with In Vitro Lytic Activity against Bovine Mastitis Streptococcus uberis
by Niels Vander Elst, Sara B. Linden, Rob Lavigne, Evelyne Meyer, Yves Briers and Daniel C. Nelson
Antibiotics 2020, 9(9), 621; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9090621 - 19 Sep 2020
Cited by 19 | Viewed by 4772
Abstract
Bovine mastitis, an infection of the cow’s mammary gland, is frequently caused by Streptococcus uberis and causes major economic losses in the dairy industry. The intramammary administration of antibiotics currently remains the predominant preventive and therapeutic measure. These antimicrobial compounds, of which some [...] Read more.
Bovine mastitis, an infection of the cow’s mammary gland, is frequently caused by Streptococcus uberis and causes major economic losses in the dairy industry. The intramammary administration of antibiotics currently remains the predominant preventive and therapeutic measure. These antimicrobial compounds, of which some are considered critical in human health care, are frequently applied as dry therapy resulting in their consistent overuse. Therefore, the use of antibiotics in the dairy sector is being questioned. We here identified two endolysins, i.e., PlySs2 and PlySs9, respectively derived from Streptococcus suis serotype-2 and -9 prophages, with lytic activity against S. uberis in an in vitro setting. Both endolysins gave clear lysis zones in spot-on-plate assays and caused a reduction of the optical density in a turbidity reduction assay. In depth characterization identified PlySs9 as the more potent endolysin over PlySs2 with a lower MIC value and about one additional log of killing. PlySs2 and PlySs9 were challenged to a panel of subclinical and clinical S. uberis milk isolates and were both able to lyse all strains tested. Molecular dissection of these endolysins in catalytic and cell wall binding subdomains resulted in major loss of killing and binding activity, respectively. Taken together, we here propose PlySs2 and PlySs9 as candidate compounds to the current antimicrobial arsenal known against bovine mastitis-causing S. uberis as future add-on or replacement strategy to the currently used intramammary antibiotics. Full article
(This article belongs to the Special Issue Bacteriophages: An Inspiration for the Development of New Antimicrobial and Antibiofilm Agents)
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11 pages, 3133 KiB  
Article
A Localized Phage-Based Antimicrobial System: Effect of Alginate on Phage Desorption from β-TCP Ceramic Bone Substitutes
by Rached Ismail, Natalia D. Dorighello Carareto, Jean-Christophe Hornez and Franck Bouchart
Antibiotics 2020, 9(9), 560; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9090560 - 31 Aug 2020
Cited by 3 | Viewed by 2437
Abstract
Tricalcium phosphate (TCP) is a prosthetic material commonly used as a bone substitute to repair osteoarticular diseases and injuries. In this type of bone reconstruction surgery, antibiotics remain the common preventive and therapeutic treatment for bacterial infection. Nevertheless, the emergence of multi-resistant strains [...] Read more.
Tricalcium phosphate (TCP) is a prosthetic material commonly used as a bone substitute to repair osteoarticular diseases and injuries. In this type of bone reconstruction surgery, antibiotics remain the common preventive and therapeutic treatment for bacterial infection. Nevertheless, the emergence of multi-resistant strains requires complimentary or alternative treatments. Today, one of the promising alternative approaches is phage therapy. Phages are bacterial viruses that have several advantages over chemotherapy, such as the specificity of bacterial strain, the absence of side effects, and a rapid response. In this work, we studied the impact of alginate hydrogels for overlaying λvir-phage-loaded β-TCP ceramic bone substitutes, delaying the phage desorption. The results show that the use of a 1% alginate–CaCl2 hydrogel overlapping the β-TCP ceramic pellets leads to higher initial phage concentration on the material and extends the released time of phages to two weeks when compared with control pellets. These alginate-coated biomaterials also generate faster bacterial lysis kinetics and could therefore be a good practical prosthetic device for bone and joint surgeries by allowing local treatment of bacterial infections with phage therapy for a longer period of time. Full article
(This article belongs to the Special Issue Bacteriophages: An Inspiration for the Development of New Antimicrobial and Antibiofilm Agents)
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8 pages, 1116 KiB  
Article
Encapsulation of the Antistaphylococcal Endolysin LysRODI in pH-Sensitive Liposomes
by Silvia Portilla, Lucía Fernández, Diana Gutiérrez, Ana Rodríguez and Pilar García
Antibiotics 2020, 9(5), 242; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9050242 - 09 May 2020
Cited by 33 | Viewed by 4559
Abstract
Phage lysins are promising new therapeutics against multidrug-resistant bacteria. These so-called enzybiotics offer, amongst their most notable advantages, high target specificity and low resistance development. Moreover, there are numerous recent and ongoing studies aimed at demonstrating the efficacy and safety of endolysins in [...] Read more.
Phage lysins are promising new therapeutics against multidrug-resistant bacteria. These so-called enzybiotics offer, amongst their most notable advantages, high target specificity and low resistance development. Moreover, there are numerous recent and ongoing studies aimed at demonstrating the efficacy and safety of endolysins in animal models or even in clinical trials. Nonetheless, as is the case for other antimicrobials, it is important to assess potential strategies that may broaden their potential applications or improve their stability. Encapsulation, for instance, has given very good results for some antibiotics. This study sought to evaluate the feasibility of encapsulating an endolysin against the opportunistic human pathogen Staphylococcus aureus, one of the most problematic bacteria in the context of the current antibiotic resistance crisis. Endolysin LysRODI has antimicrobial activity against many S. aureus strains from different sources, including methicillin-resistant S. aureus (MRSA) isolates. Here, this protein was encapsulated in pH-sensitive liposomes with an efficacy of approximately 47%, retaining its activity after being released from the nanocapsules. Additionally, the encapsulated endolysin effectively reduced S. aureus cell counts by > 2log units in both planktonic cultures and biofilms upon incubation at pH 5. These results demonstrate the viability of LysRODI encapsulation in liposomes for its targeted delivery under mild acidic conditions. Full article
(This article belongs to the Special Issue Bacteriophages: An Inspiration for the Development of New Antimicrobial and Antibiofilm Agents)
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12 pages, 5901 KiB  
Article
Development of Staphylococcus Enzybiotics: The Ph28 Gene of Staphylococcus epidermidis Phage PH15 Is a Two-Domain Endolysin
by Magdy Mohamed Muharram, Ashraf Tawfik Abulhamd, Mohammed F. Aldawsari, Mohamed Hamed Alqarni and Nikolaos E. Labrou
Antibiotics 2020, 9(4), 148; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9040148 - 30 Mar 2020
Cited by 5 | Viewed by 2566
Abstract
Given the worldwide increase in antibiotic resistant bacteria, bacteriophage derived endolysins represent a very promising new alternative class of antibacterials in the fight against infectious diseases. Endolysins are able to degrade the prokaryotic cell wall, and therefore have potential to be exploited for [...] Read more.
Given the worldwide increase in antibiotic resistant bacteria, bacteriophage derived endolysins represent a very promising new alternative class of antibacterials in the fight against infectious diseases. Endolysins are able to degrade the prokaryotic cell wall, and therefore have potential to be exploited for biotechnological and medical purposes. Staphylococcus epidermidis is a Gram-positive multidrug-resistant (MDR) bacterium of human skin. It is a health concern as it is involved in nosocomial infections. Genome-based screening approach of the complete genome of Staphylococcus virus PH15 allowed the identification of an endolysin gene (Ph28; NCBI accession number: YP_950690). Bioinformatics analysis of the Ph28 protein predicted that it is a two-domain enzyme composed by a CHAP (22-112) and MurNAc-LAA (171-349) domain. Phylogenetic analysis and molecular modelling studies revealed the structural and evolutionary features of both domains. The MurNAc-LAA domain was cloned, and expressed in E. coli BL21 (DE3). In turbidity reduction assays, the recombinant enzyme can lyse more efficiently untreated S. epidermidis cells, compared to other Staphylococcus strains, suggesting enhanced specificity for S. epidermidis. These results suggest that the MurNAc-LAA domain from Ph28 endolysin may represent a promising new enzybiotic. Full article
(This article belongs to the Special Issue Bacteriophages: An Inspiration for the Development of New Antimicrobial and Antibiofilm Agents)
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Review

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14 pages, 1776 KiB  
Review
Genetic and Chemical Engineering of Phages for Controlling Multidrug-Resistant Bacteria
by Dingming Guo, Jingchao Chen, Xueyang Zhao, Yanan Luo, Menglu Jin, Fenxia Fan, Chaiwoo Park, Xiaoman Yang, Chuqing Sun, Jin Yan, Weihua Chen and Zhi Liu
Antibiotics 2021, 10(2), 202; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10020202 - 19 Feb 2021
Cited by 17 | Viewed by 4684
Abstract
Along with the excessive use of antibiotics, the emergence and spread of multidrug-resistant bacteria has become a public health problem and a great challenge vis-à-vis the control and treatment of bacterial infections. As the natural predators of bacteria, phages have reattracted researchers’ attentions. [...] Read more.
Along with the excessive use of antibiotics, the emergence and spread of multidrug-resistant bacteria has become a public health problem and a great challenge vis-à-vis the control and treatment of bacterial infections. As the natural predators of bacteria, phages have reattracted researchers’ attentions. Phage therapy is regarded as one of the most promising alternative strategies to fight pathogens in the post-antibiotic era. Recently, genetic and chemical engineering methods have been applied in phage modification. Among them, genetic engineering includes the expression of toxin proteins, modification of host recognition receptors, and interference of bacterial phage-resistant pathways. Chemical engineering, meanwhile, involves crosslinking phage coats with antibiotics, antimicrobial peptides, heavy metal ions, and photothermic matters. Those advances greatly expand the host range of phages and increase their bactericidal efficiency, which sheds light on the application of phage therapy in the control of multidrug-resistant pathogens. This review reports on engineered phages through genetic and chemical approaches. Further, we present the obstacles that this novel antimicrobial has incurred. Full article
(This article belongs to the Special Issue Bacteriophages: An Inspiration for the Development of New Antimicrobial and Antibiofilm Agents)
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