Beyond Phages: Exploring Endolysins as Key Players in the Future of Antibacterial Therapeutics

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

Deadline for manuscript submissions: 31 July 2025 | Viewed by 2328

Special Issue Editor


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Guest Editor
Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Paseo Río Linares, sn, 33300 Villaviciosa, Asturias, Spain
Interests: bacteriophages; endolysins; phage therapy; biocontrol; Staphylococcus aureus; biofilms
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Special Issue Information

Dear Colleagues,

Phage endolysins are enzymes produced by bacteriophages (viruses that infect bacteria) during the final stages of the lytic cycle. These enzymes play a crucial role in the phage lifecycle by breaking down the bacterial cell wall from the inside, leading to the release of newly formed phage particles. Endolysins have gained attention for their potential as novel antimicrobials due to notable advantages, such as their specificity, rapid bactericidal action, synergy with antibiotics, and low likelihood of resistance. Research into the development and application of endolysins as antimicrobials is ongoing, and they hold promise as a valuable addition to the arsenal of antimicrobial strategies, particularly in the context of addressing antibiotic-resistant bacterial infections. The use of endolysins in phage therapy still needs some research to address challenges, optimize treatment protocols, and gather robust clinical evidence. Some therapeutic issues are related to dosing, administration routes, bioavailability, immunogenicity, and ensuring safety and efficacy across diverse patient populations. This Special Issue will explore recent research supporting, but not limited to, the following: (1) clinical evidence on the efficacy and safety of endolysins in humans, (2) progress in developing regulatory frameworks and standards for approval (production, quality control, and clinical use), and (3) development in scaling up the production for commercial use and addressing associated cost.

Dr. Pilar García Suárez
Guest Editor

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Keywords

  • endolysins
  • bacteriophages
  • phage therapy
  • antimicrobial resistance
  • clinical trials
  • regulatory framework

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Published Papers (2 papers)

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Research

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14 pages, 2585 KiB  
Article
Characterization of Clostridium perfringens Phage Endolysin PlyDolk21
by Suyoung Seo, Bokyung Son and Minsuk Kong
Antibiotics 2025, 14(1), 81; https://doi.org/10.3390/antibiotics14010081 - 13 Jan 2025
Viewed by 1292
Abstract
Background: Clostridium perfringens is a significant cause of food poisoning. Broad-spectrum antibiotics, commonly used to control C. perfringens, are becoming less effective due to the rise of antibiotic-resistant strains, necessitating alternative control strategies. Methods: A C. perfringens-infecting bacteriophage, Dolk21, and [...] Read more.
Background: Clostridium perfringens is a significant cause of food poisoning. Broad-spectrum antibiotics, commonly used to control C. perfringens, are becoming less effective due to the rise of antibiotic-resistant strains, necessitating alternative control strategies. Methods: A C. perfringens-infecting bacteriophage, Dolk21, and its endolysin, PlyDolk21, were isolated and characterized. The lytic activity of PlyDolk21 was assessed in comparison to its catalytic domain alone. Both PlyDolk21 and its cell wall binding domain (CBD) were evaluated in beef and milk for their antimicrobial activity and cell wall binding activity, respectively. Results: While phage Dolk21 was specific to certain C. perfringens strains, PlyDolk21 exhibited lytic activity against all C. perfringens strains tested. The full-length PlyDolk21 showed stronger lytic activity compared to its catalytic domain alone. PlyDolk21_CBD successfully bound to C. perfringens in vitro and in foods. Additionally, PlyDolk21 effectively reduced the viable cell counts of C. perfringens by 3-log in beef soup and milk samples. Conclusions: This study demonstrates that PlyDolk21 and its CBD hold potential as a biocontrol and detection agent targeting C. perfringens in various food matrices. Full article
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Review

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30 pages, 4645 KiB  
Review
New Perspectives in the Fight Against Multidrug-Resistant Bacteria: The Potential of Endolysin Biocomposites
by Carlos E. Camacho-González, Cesar S. Cardona-Felix, Alejandro Pérez-Larios, Víctor M. Zamora-Gasga, Sonia G. Sáyago-Ayerdi and Jorge A. Sánchez-Burgos
Antibiotics 2025, 14(5), 457; https://doi.org/10.3390/antibiotics14050457 - 30 Apr 2025
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Abstract
The growing threat of multidrug-resistant bacteria requires innovative therapies beyond traditional antibiotics. This review highlights the potential of endolysin biocomposites using alginate oligosaccharides (AOSs) and modified cellulose (CL) as stabilizers. AOSs could enhance endolysin stability and potentially support colonic fermentation, producing short-chain fatty [...] Read more.
The growing threat of multidrug-resistant bacteria requires innovative therapies beyond traditional antibiotics. This review highlights the potential of endolysin biocomposites using alginate oligosaccharides (AOSs) and modified cellulose (CL) as stabilizers. AOSs could enhance endolysin stability and potentially support colonic fermentation, producing short-chain fatty acids that may synergize with endolysins to combat pathogens and improve gut health. KZ144 and LysPA26 are proposed as optimal candidates for their broad pH range, divalent cation tolerance, and potential effectiveness against Gram-positive and Gram-negative pathogens. Integrating AOSs and CL into biocomposites could offer a novel dual-action strategy against gastrointestinal diseases while potentially reducing antibiotic dependence. Full article
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