Diversity, Dynamics and Therapeutic Application of <i>Clostridioides difficile</i> Bacteriophages
<i>Clostridioides difficile</i> causes antibiotic-induced diarrhoea and pseudomembranous colitis in humans and animals. Current conventional treatment relies solely on antibiotics, but <i>C. difficile</i> infection (CDI) cases remain persistently high with concomitant increas...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/12/2772 |
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| author | Janet Y. Nale Anisha M. Thanki Srwa J. Rashid Jinyu Shan Gurinder K. Vinner Ahmed S. A. Dowah Jeffrey K. J. Cheng Thomas Sicheritz-Pontén Martha R. J. Clokie |
| author_facet | Janet Y. Nale Anisha M. Thanki Srwa J. Rashid Jinyu Shan Gurinder K. Vinner Ahmed S. A. Dowah Jeffrey K. J. Cheng Thomas Sicheritz-Pontén Martha R. J. Clokie |
| author_sort | Janet Y. Nale |
| collection | DOAJ |
| description | <i>Clostridioides difficile</i> causes antibiotic-induced diarrhoea and pseudomembranous colitis in humans and animals. Current conventional treatment relies solely on antibiotics, but <i>C. difficile</i> infection (CDI) cases remain persistently high with concomitant increased recurrence often due to the emergence of antibiotic-resistant strains. Antibiotics used in treatment also induce gut microbial imbalance; therefore, novel therapeutics with improved target specificity are being investigated. Bacteriophages (phages) kill bacteria with precision, hence are alternative therapeutics for the targeted eradication of the pathogen. Here, we review current progress in <i>C. difficile</i> phage research. We discuss tested strategies of isolating <i>C. difficile</i> phages directly, and via enrichment methods from various sample types and through antibiotic induction to mediate prophage release. We also summarise phenotypic phage data that reveal their morphological, genetic diversity, and various ways they impact their host physiology and pathogenicity during infection and lysogeny. Furthermore, we describe the therapeutic development of phages through efficacy testing in different in vitro, ex vivo and in vivo infection models. We also discuss genetic modification of phages to prevent horizontal gene transfer and improve lysis efficacy and formulation to enhance stability and delivery of the phages. The goal of this review is to provide a more in-depth understanding of <i>C. difficile</i> phages and theoretical and practical knowledge on pre-clinical, therapeutic evaluation of the safety and effectiveness of phage therapy for CDI. |
| first_indexed | 2024-03-09T15:44:46Z |
| format | Article |
| id | doaj.art-65be4a4b2f5249e389db8d0e3dd0531f |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T15:44:46Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-65be4a4b2f5249e389db8d0e3dd0531f2023-11-24T18:39:24ZengMDPI AGViruses1999-49152022-12-011412277210.3390/v14122772Diversity, Dynamics and Therapeutic Application of <i>Clostridioides difficile</i> BacteriophagesJanet Y. Nale0Anisha M. Thanki1Srwa J. Rashid2Jinyu Shan3Gurinder K. Vinner4Ahmed S. A. Dowah5Jeffrey K. J. Cheng6Thomas Sicheritz-Pontén7Martha R. J. Clokie8Centre for Epidemiology and Planetary Health, Department of Veterinary and Animal Science, Scotland’s Rural College, Inverness IV2 5NA, UKDepartment of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UKDepartment of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UKDepartment of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UKDepartment of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UKDepartment of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UKSchool of Life Sciences, University of Warwick, Coventry CV4 7AL, UKCenter for Evolutionary Hologenomics, The Globe Institute, University of Copenhagen, 1353 Copenhagen, DenmarkDepartment of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK<i>Clostridioides difficile</i> causes antibiotic-induced diarrhoea and pseudomembranous colitis in humans and animals. Current conventional treatment relies solely on antibiotics, but <i>C. difficile</i> infection (CDI) cases remain persistently high with concomitant increased recurrence often due to the emergence of antibiotic-resistant strains. Antibiotics used in treatment also induce gut microbial imbalance; therefore, novel therapeutics with improved target specificity are being investigated. Bacteriophages (phages) kill bacteria with precision, hence are alternative therapeutics for the targeted eradication of the pathogen. Here, we review current progress in <i>C. difficile</i> phage research. We discuss tested strategies of isolating <i>C. difficile</i> phages directly, and via enrichment methods from various sample types and through antibiotic induction to mediate prophage release. We also summarise phenotypic phage data that reveal their morphological, genetic diversity, and various ways they impact their host physiology and pathogenicity during infection and lysogeny. Furthermore, we describe the therapeutic development of phages through efficacy testing in different in vitro, ex vivo and in vivo infection models. We also discuss genetic modification of phages to prevent horizontal gene transfer and improve lysis efficacy and formulation to enhance stability and delivery of the phages. The goal of this review is to provide a more in-depth understanding of <i>C. difficile</i> phages and theoretical and practical knowledge on pre-clinical, therapeutic evaluation of the safety and effectiveness of phage therapy for CDI.https://www.mdpi.com/1999-4915/14/12/2772<i>Clostridioides difficile</i><i>Clostridium difficile</i>bacteriophagesphagesphage therapyinfection models |
| spellingShingle | Janet Y. Nale Anisha M. Thanki Srwa J. Rashid Jinyu Shan Gurinder K. Vinner Ahmed S. A. Dowah Jeffrey K. J. Cheng Thomas Sicheritz-Pontén Martha R. J. Clokie Diversity, Dynamics and Therapeutic Application of <i>Clostridioides difficile</i> Bacteriophages Viruses <i>Clostridioides difficile</i> <i>Clostridium difficile</i> bacteriophages phages phage therapy infection models |
| title | Diversity, Dynamics and Therapeutic Application of <i>Clostridioides difficile</i> Bacteriophages |
| title_full | Diversity, Dynamics and Therapeutic Application of <i>Clostridioides difficile</i> Bacteriophages |
| title_fullStr | Diversity, Dynamics and Therapeutic Application of <i>Clostridioides difficile</i> Bacteriophages |
| title_full_unstemmed | Diversity, Dynamics and Therapeutic Application of <i>Clostridioides difficile</i> Bacteriophages |
| title_short | Diversity, Dynamics and Therapeutic Application of <i>Clostridioides difficile</i> Bacteriophages |
| title_sort | diversity dynamics and therapeutic application of i clostridioides difficile i bacteriophages |
| topic | <i>Clostridioides difficile</i> <i>Clostridium difficile</i> bacteriophages phages phage therapy infection models |
| url | https://www.mdpi.com/1999-4915/14/12/2772 |
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