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Viruses 2019, 11(2), 96; https://doi.org/10.3390/v11020096

The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole

1
Laboratory of Applied Biotechnology, Department of Biotechnology, Ghent University, Valentin Vaerwijckweg 1, B-9000 Ghent, Belgium
2
Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt
3
MeBioS-Biosensors group, Department of Biosystems, KU Leuven, Willem de Croylaan 42, B-3001 Leuven, Belgium
4
Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Kasteelpark Arenberg 21, B-3001 Leuven, Belgium
5
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Menoufia University, Shebin ElKoum 51132, Egypt
*
Author to whom correspondence should be addressed.
Received: 18 December 2018 / Revised: 16 January 2019 / Accepted: 22 January 2019 / Published: 24 January 2019
(This article belongs to the Special Issue Phage Lytic Enzymes and Their Applications)
Full-Text   |   PDF [255 KB, uploaded 24 January 2019]

Abstract

The therapeutic potential of phages has been considered since their first identification more than a century ago. The evident concept of using a natural predator to treat bacterial infections has, however, since then been challenged considerably. Initially, the vast success of antibiotics almost eliminated the study of phages for therapy. Upon the renaissance of phage therapy research, the most provocative and unique properties of phages such as high specificity, self-replication and co-evolution prohibited a rapid preclinical and clinical development. On the one hand, the typical trajectory followed by small molecule antibiotics could not be simply translated into the preclinical analysis of phages, exemplified by the need for complex broad spectrum or personalized phage cocktails of high purity and the more complex pharmacokinetics. On the other hand, there was no fitting regulatory framework to deal with flexible and sustainable phage therapy approaches, including the setup and approval of adequate clinical trials. While significant advances are incrementally made to eliminate these hurdles, phage-inspired antibacterials have progressed in the slipstream of phage therapy, benefiting from the lack of hurdles that are typically associated with phage therapy. Most advanced are phage lytic enzymes that kill bacteria through peptidoglycan degradation and osmotic lysis. Both phages and their lytic enzymes are now widely considered as safe and have now progressed to clinical phase II to show clinical efficacy as pharmaceutical. Yet, more initiatives are needed to fill the clinical pipeline to beat the typical attrition rates of clinical evaluation and to come to a true evaluation of phages and phage lytic enzymes in the clinic. View Full-Text
Keywords: phage; lytic enzyme; endolysin; antibacterial; antibiotic; preclinical analysis; clinical trial phage; lytic enzyme; endolysin; antibacterial; antibiotic; preclinical analysis; clinical trial
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Abdelkader, K.; Gerstmans, H.; Saafan, A.; Dishisha, T.; Briers, Y. The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole. Viruses 2019, 11, 96.

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