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This article is part of the Research Topic Gram-positive phages: From isolation to application

Review ARTICLE

Front. Microbiol., 28 April 2014 | http://dx.doi.org/10.3389/fmicb.2014.00184

Clostridium difficile phages: still difficult?

  • Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK

Phages that infect Clostridium difficile were first isolated for typing purposes in the 1980s, but their use was short lived. However, the rise of C. difficile epidemics over the last decade has triggered a resurgence of interest in using phages to combat this pathogen. Phage therapy is an attractive treatment option for C. difficile infection, however, developing suitable phages is challenging. In this review we summarize the difficulties faced by researchers in this field, and we discuss the solutions and strategies used for the development of C. difficile phages for use as novel therapeutics. Epidemiological data has highlighted the diversity and distribution of C. difficile, and shown that novel strains continue to emerge in clinical settings. In parallel with epidemiological studies, advances in molecular biology have bolstered our understanding of C. difficile biology, and our knowledge of phage–host interactions in other bacterial species. These three fields of biology have therefore paved the way for future work on C. difficile phages to progress and develop. Benefits of using C. difficile phages as therapeutic agents include the fact that they have highly specific interactions with their bacterial hosts. Studies also show that they can reduce bacterial numbers in both in vitro and in vivo systems. Genetic analysis has revealed the genomic diversity among these phages and provided an insight into their taxonomy and evolution. No strictly virulent C. difficile phages have been reported and this contributes to the difficulties with their therapeutic exploitation. Although treatment approaches using the phage-encoded endolysin protein have been explored, the benefits of using “whole-phages” are such that they remain a major research focus. Whilst we don’t envisage working with C. difficile phages will be problem-free, sufficient study should inform future strategies to facilitate their development to combat this problematic pathogen.

Keywords: Clostridium difficile, phage therapy, phage evolution, genomics, lysogeny, gut pathogen, nosocomial

Citation: Hargreaves KR and Clokie MRJ (2014) Clostridium difficile phages: still difficult? Front. Microbiol. 5:184. doi: 10.3389/fmicb.2014.00184

Received: 31 January 2014; Accepted: 03 April 2014;
Published online: 28 April 2014.

Edited by:

Jennifer Mahony, University College Cork, Ireland

Reviewed by:

Stephen Tobias Abedon, The Ohio State University, USA
Britt Louise Koskella, University of Exeter, UK

Copyright © 2014 Hargreaves and Clokie. 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) or licensor 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.

*Correspondence: Martha R. J. Clokie, Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester LE1 9HN, UK e-mail: mrjc1@le.ac.uk