[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Better together: bacteriophage combinations significantly reduce Clostridium difficile growth in vitro and proliferation in vivo [ ]
Janet Y. Nale a, Janice Spencer b, Katherine R. Hargreaves a, Anthony M. Buckley b, Przemysław Trzepiński a, Gillian R. Douce b# and Martha R. J. Clokie a#
Author Affiliations: aDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester, England, UK. bInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graham Davies Building, University Place, University of Glasgow, Scotland, UK
Microbiome dysbiosis caused by antibiotic treatment has been associated with both the susceptibility and relapsing of Clostridium difficile infection (CDI). Bacteriophage (phage) therapy offers target specificity and dose amplification in situ, but few studies have focused on their use in CDI treatment. This mainly reflects the lack of strictly virulent phages that target this pathogen. Whilst it is widely accepted that temperate phages are unsuitable for therapeutic purposes due to their transduction potential, analysis of seven C. difficile phages confirmed that this impact could be curtailed by the application of multiple phage types. Here, host range analysis of six myoviruses and one siphovirus was conducted on 80 strains representing 21 major epidemic and clinically severe ribotypes. The phages had complementary coverage; lysing 18 and 62 of the ribotypes and strains tested respectively. Single-phage treatments of ribotypes 076, 014/020 and 027 strains showed an initial reduction in bacterial load followed by emergence of phage-resistant colonies. However, these colonies remained susceptible to phage infection with an unrelated phage. In contrast, specific phage combinations caused complete lysis of C. difficile in vitro and prevented the appearance of resistant/lysogenic clones. Using a hamster model, oral delivery of optimized phage combinations resulted in reduced C. difficile colonization 36 h post-infection. Interestingly, free phages were recovered from the bowel at this time. In a challenge model of the disease, phage treatment delayed the onset of symptoms by 33 h compared to untreated animals. These data demonstrate the therapeutic potential of phage combinations to treat CDI.
Copyright © 2015 Nale et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 International license.
Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Clostridium Difficile; Bacteriophages.