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The long and sinuous road to phage-based therapy of Clostridioides difficile infections

With the antibiotic crisis and the rise in antimicrobial resistance worldwide, new therapeutic alternatives are urgently needed. Phage therapy represents one of the most promising alternatives but for some pathogens, such as Clostridioides difficile, important challenges are being faced. The perspec...

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Autores principales: Umansky, Andrew A., Fortier, Louis Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481535/
https://www.ncbi.nlm.nih.gov/pubmed/37680620
http://dx.doi.org/10.3389/fmed.2023.1259427
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author Umansky, Andrew A.
Fortier, Louis Charles
author_facet Umansky, Andrew A.
Fortier, Louis Charles
author_sort Umansky, Andrew A.
collection PubMed
description With the antibiotic crisis and the rise in antimicrobial resistance worldwide, new therapeutic alternatives are urgently needed. Phage therapy represents one of the most promising alternatives but for some pathogens, such as Clostridioides difficile, important challenges are being faced. The perspective of phage therapy to treat C. difficile infections is complicated by the fact that no strictly lytic phages have been identified so far, and current temperate phages generally have a narrow host range. C. difficile also harbors multiple antiphage mechanisms, and the bacterial genome is often a host of one or multiple prophages that can interfere with lytic phage infection. Nevertheless, due to recent advances in phage host receptor recognition and improvements in genetic tools to manipulate phage genomes, it is now conceivable to genetically engineer C. difficile phages to make them suitable for phage therapy. Other phage-based alternatives such as phage endolysins and phage tail-like bacteriocins (avidocins) are also being investigated but these approaches also have their own limitations and challenges. Last but not least, C. difficile produces spores that are resistant to phage attacks and all current antibiotics, and this complicates therapeutic interventions. This mini-review gives a brief historical overview of phage work that has been carried out in C. difficile, presents recent advances in the field, and addresses the most important challenges that are being faced, with potential solutions.
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spelling pubmed-104815352023-09-07 The long and sinuous road to phage-based therapy of Clostridioides difficile infections Umansky, Andrew A. Fortier, Louis Charles Front Med (Lausanne) Medicine With the antibiotic crisis and the rise in antimicrobial resistance worldwide, new therapeutic alternatives are urgently needed. Phage therapy represents one of the most promising alternatives but for some pathogens, such as Clostridioides difficile, important challenges are being faced. The perspective of phage therapy to treat C. difficile infections is complicated by the fact that no strictly lytic phages have been identified so far, and current temperate phages generally have a narrow host range. C. difficile also harbors multiple antiphage mechanisms, and the bacterial genome is often a host of one or multiple prophages that can interfere with lytic phage infection. Nevertheless, due to recent advances in phage host receptor recognition and improvements in genetic tools to manipulate phage genomes, it is now conceivable to genetically engineer C. difficile phages to make them suitable for phage therapy. Other phage-based alternatives such as phage endolysins and phage tail-like bacteriocins (avidocins) are also being investigated but these approaches also have their own limitations and challenges. Last but not least, C. difficile produces spores that are resistant to phage attacks and all current antibiotics, and this complicates therapeutic interventions. This mini-review gives a brief historical overview of phage work that has been carried out in C. difficile, presents recent advances in the field, and addresses the most important challenges that are being faced, with potential solutions. Frontiers Media S.A. 2023-08-23 /pmc/articles/PMC10481535/ /pubmed/37680620 http://dx.doi.org/10.3389/fmed.2023.1259427 Text en Copyright © 2023 Umansky and Fortier. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Umansky, Andrew A.
Fortier, Louis Charles
The long and sinuous road to phage-based therapy of Clostridioides difficile infections
title The long and sinuous road to phage-based therapy of Clostridioides difficile infections
title_full The long and sinuous road to phage-based therapy of Clostridioides difficile infections
title_fullStr The long and sinuous road to phage-based therapy of Clostridioides difficile infections
title_full_unstemmed The long and sinuous road to phage-based therapy of Clostridioides difficile infections
title_short The long and sinuous road to phage-based therapy of Clostridioides difficile infections
title_sort long and sinuous road to phage-based therapy of clostridioides difficile infections
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481535/
https://www.ncbi.nlm.nih.gov/pubmed/37680620
http://dx.doi.org/10.3389/fmed.2023.1259427
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