Diversity, Dynamics and Therapeutic Application of Clostridioides difficile Bacteriophages

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*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Clostridioides difficile causes antibiotic-induced diarrhoea and pseudomembranous colitis in humans and animals. Current conventional treatment relies solely on antibiotics, but C. difficile 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 C. difficile phage research. We discuss tested strategies of isolating C. difficile 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 C. difficile phages and theoretical and practical knowledge on pre-clinical, therapeutic evaluation of the safety and effectiveness of phage therapy for CDI.

Original languageEnglish
Article number2772
JournalViruses
Volume14
Issue number12
Early online date12 Dec 2022
DOIs
Publication statusFirst published - 12 Dec 2022

Bibliographical note

Funding Information:
This work was funded by Biotechnology and Biological Sciences Research Council (BBSRC), grant number RM38G0140 awarded to M.R.J.C.

Publisher Copyright:
© 2022 by the authors.

Keywords

  • bacteriophages
  • Clostridioides difficile
  • Clostridium difficile
  • infection models
  • phage therapy
  • phages
  • Animals
  • Prophages/genetics
  • Humans
  • Anti-Bacterial Agents/therapeutic use
  • Clostridioides
  • Bacteriophages/genetics

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