The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole
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 eli...
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doaj-230056f73a8b4c73a78c3814753063282020-11-25T00:33:26ZengMDPI AGViruses1999-49152019-01-011129610.3390/v11020096v11020096The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the WholeKarim Abdelkader0Hans Gerstmans1Amal Saafan2Tarek Dishisha3Yves Briers4Laboratory of Applied Biotechnology, Department of Biotechnology, Ghent University, Valentin Vaerwijckweg 1, B-9000 Ghent, BelgiumLaboratory of Applied Biotechnology, Department of Biotechnology, Ghent University, Valentin Vaerwijckweg 1, B-9000 Ghent, BelgiumDepartment of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, EgyptLaboratory of Applied Biotechnology, Department of Biotechnology, Ghent University, Valentin Vaerwijckweg 1, B-9000 Ghent, BelgiumThe 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.https://www.mdpi.com/1999-4915/11/2/96phagelytic enzymeendolysinantibacterialantibioticpreclinical analysisclinical trial |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karim Abdelkader Hans Gerstmans Amal Saafan Tarek Dishisha Yves Briers |
spellingShingle |
Karim Abdelkader Hans Gerstmans Amal Saafan Tarek Dishisha Yves Briers The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole Viruses phage lytic enzyme endolysin antibacterial antibiotic preclinical analysis clinical trial |
author_facet |
Karim Abdelkader Hans Gerstmans Amal Saafan Tarek Dishisha Yves Briers |
author_sort |
Karim Abdelkader |
title |
The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole |
title_short |
The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole |
title_full |
The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole |
title_fullStr |
The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole |
title_full_unstemmed |
The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole |
title_sort |
preclinical and clinical progress of bacteriophages and their lytic enzymes: the parts are easier than the whole |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2019-01-01 |
description |
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. |
topic |
phage lytic enzyme endolysin antibacterial antibiotic preclinical analysis clinical trial |
url |
https://www.mdpi.com/1999-4915/11/2/96 |
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