Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model
Clostridium difficile infection (CDI) is a major cause of infectious diarrhea. Conventional antibiotics are not universally effective for all ribotypes, and can trigger dysbiosis, resistance and recurrent infection. Thus, novel therapeutics are needed to replace and/or supplement the current antibio...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-02-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2079-6382/7/1/13 |
| _version_ | 1818875653626265600 |
|---|---|
| author | Janet Y. Nale Tamsin A. Redgwell Andrew Millard Martha R. J. Clokie |
| author_facet | Janet Y. Nale Tamsin A. Redgwell Andrew Millard Martha R. J. Clokie |
| author_sort | Janet Y. Nale |
| collection | DOAJ |
| description | Clostridium difficile infection (CDI) is a major cause of infectious diarrhea. Conventional antibiotics are not universally effective for all ribotypes, and can trigger dysbiosis, resistance and recurrent infection. Thus, novel therapeutics are needed to replace and/or supplement the current antibiotics. Here, we describe the activity of an optimised 4-phage cocktail to clear cultures of a clinical ribotype 014/020 strain in fermentation vessels spiked with combined fecal slurries from four healthy volunteers. After 5 h, we observed ~6-log reductions in C. difficile abundance in the prophylaxis regimen and complete C. difficile eradication after 24 h following prophylactic or remedial regimens. Viability assays revealed that commensal enterococci, bifidobacteria, lactobacilli, total anaerobes, and enterobacteria were not affected by either regimens, but a ~2-log increase in the enterobacteria, lactobacilli, and total anaerobe abundance was seen in the phage-only-treated vessel compared to other treatments. The impact of the phage treatments on components of the microbiota was further assayed using metagenomic analysis. Together, our data supports the therapeutic application of our optimised phage cocktail to treat CDI. Also, the increase in specific commensals observed in the phage-treated control could prevent further colonisation of C. difficile, and thus provide protection from infection being able to establish. |
| first_indexed | 2024-12-19T13:29:55Z |
| format | Article |
| id | doaj.art-0e0cea44fea3499b8b8f4b1835bd56e0 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-12-19T13:29:55Z |
| publishDate | 2018-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-0e0cea44fea3499b8b8f4b1835bd56e02022-12-21T20:19:26ZengMDPI AGAntibiotics2079-63822018-02-01711310.3390/antibiotics7010013antibiotics7010013Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation ModelJanet Y. Nale0Tamsin A. Redgwell1Andrew Millard2Martha R. J. Clokie3Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UKSchool of Life Sciences, University of Warwick, Coventry CV4 7AL, UKDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UKDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, UKClostridium difficile infection (CDI) is a major cause of infectious diarrhea. Conventional antibiotics are not universally effective for all ribotypes, and can trigger dysbiosis, resistance and recurrent infection. Thus, novel therapeutics are needed to replace and/or supplement the current antibiotics. Here, we describe the activity of an optimised 4-phage cocktail to clear cultures of a clinical ribotype 014/020 strain in fermentation vessels spiked with combined fecal slurries from four healthy volunteers. After 5 h, we observed ~6-log reductions in C. difficile abundance in the prophylaxis regimen and complete C. difficile eradication after 24 h following prophylactic or remedial regimens. Viability assays revealed that commensal enterococci, bifidobacteria, lactobacilli, total anaerobes, and enterobacteria were not affected by either regimens, but a ~2-log increase in the enterobacteria, lactobacilli, and total anaerobe abundance was seen in the phage-only-treated vessel compared to other treatments. The impact of the phage treatments on components of the microbiota was further assayed using metagenomic analysis. Together, our data supports the therapeutic application of our optimised phage cocktail to treat CDI. Also, the increase in specific commensals observed in the phage-treated control could prevent further colonisation of C. difficile, and thus provide protection from infection being able to establish.http://www.mdpi.com/2079-6382/7/1/13Clostridium difficileClostridium difficile infectionbacteriophagesphage therapymicrobiomein vitro fermentation model |
| spellingShingle | Janet Y. Nale Tamsin A. Redgwell Andrew Millard Martha R. J. Clokie Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model Antibiotics Clostridium difficile Clostridium difficile infection bacteriophages phage therapy microbiome in vitro fermentation model |
| title | Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model |
| title_full | Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model |
| title_fullStr | Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model |
| title_full_unstemmed | Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model |
| title_short | Efficacy of an Optimised Bacteriophage Cocktail to Clear Clostridium difficile in a Batch Fermentation Model |
| title_sort | efficacy of an optimised bacteriophage cocktail to clear clostridium difficile in a batch fermentation model |
| topic | Clostridium difficile Clostridium difficile infection bacteriophages phage therapy microbiome in vitro fermentation model |
| url | http://www.mdpi.com/2079-6382/7/1/13 |
| work_keys_str_mv | AT janetynale efficacyofanoptimisedbacteriophagecocktailtoclearclostridiumdifficileinabatchfermentationmodel AT tamsinaredgwell efficacyofanoptimisedbacteriophagecocktailtoclearclostridiumdifficileinabatchfermentationmodel AT andrewmillard efficacyofanoptimisedbacteriophagecocktailtoclearclostridiumdifficileinabatchfermentationmodel AT martharjclokie efficacyofanoptimisedbacteriophagecocktailtoclearclostridiumdifficileinabatchfermentationmodel |