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Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection

OBJECTIVES: Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe(3+) saturated) bovine apo-lactoferrin (apo-bLf) and...

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Autores principales: Chilton, C. H., Crowther, G. S., Śpiewak, K., Brindell, M., Singh, G., Wilcox, M. H., Monaghan, T. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790624/
https://www.ncbi.nlm.nih.gov/pubmed/26759363
http://dx.doi.org/10.1093/jac/dkv452
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author Chilton, C. H.
Crowther, G. S.
Śpiewak, K.
Brindell, M.
Singh, G.
Wilcox, M. H.
Monaghan, T. M.
author_facet Chilton, C. H.
Crowther, G. S.
Śpiewak, K.
Brindell, M.
Singh, G.
Wilcox, M. H.
Monaghan, T. M.
author_sort Chilton, C. H.
collection PubMed
description OBJECTIVES: Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe(3+) saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe(3+) saturated) bovine holo-lactoferrin (holo-bLf) in a human in vitro gut model that simulates CDI. METHODS: Two parallel triple-stage chemostat gut models were inoculated with pooled human faeces and spiked with C. difficile spores (strain 027 210, PCR ribotype 027). Holo- or apo-bLf was instilled (5 mg/mL, once daily) for 35 days. After 7 days, clindamycin was instilled (33.9 mg/L, four times daily) to induce simulated CDI. Indigenous microflora populations, C. difficile total counts and spores, cytotoxin titres, short chain fatty acid concentrations, biometal concentrations, lactoferrin concentration and iron content of lactoferrin were monitored daily. RESULTS: In the apo-bLf model, germination of C. difficile spores occurred 6 days post instillation of clindamycin, followed by rapid vegetative cell proliferation and detectable toxin production. By contrast, in the holo-bLf model, only a modest vegetative cell population was observed until 16 days post antibiotic administration. Notably, no toxin was detected in this model. In separate batch culture experiments, holo-bLf prevented C. difficile vegetative cell growth and toxin production, whereas apo-bLf and iron alone did not. CONCLUSIONS: Holo-bLf, but not apo-bLf, delayed C. difficile growth and prevented toxin production in a human gut model of CDI. This inhibitory effect may be iron independent. These observations suggest that bLf in its iron-saturated state could be used as a novel preventative or treatment strategy for CDI.
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spelling pubmed-47906242016-03-16 Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection Chilton, C. H. Crowther, G. S. Śpiewak, K. Brindell, M. Singh, G. Wilcox, M. H. Monaghan, T. M. J Antimicrob Chemother Original Research OBJECTIVES: Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe(3+) saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe(3+) saturated) bovine holo-lactoferrin (holo-bLf) in a human in vitro gut model that simulates CDI. METHODS: Two parallel triple-stage chemostat gut models were inoculated with pooled human faeces and spiked with C. difficile spores (strain 027 210, PCR ribotype 027). Holo- or apo-bLf was instilled (5 mg/mL, once daily) for 35 days. After 7 days, clindamycin was instilled (33.9 mg/L, four times daily) to induce simulated CDI. Indigenous microflora populations, C. difficile total counts and spores, cytotoxin titres, short chain fatty acid concentrations, biometal concentrations, lactoferrin concentration and iron content of lactoferrin were monitored daily. RESULTS: In the apo-bLf model, germination of C. difficile spores occurred 6 days post instillation of clindamycin, followed by rapid vegetative cell proliferation and detectable toxin production. By contrast, in the holo-bLf model, only a modest vegetative cell population was observed until 16 days post antibiotic administration. Notably, no toxin was detected in this model. In separate batch culture experiments, holo-bLf prevented C. difficile vegetative cell growth and toxin production, whereas apo-bLf and iron alone did not. CONCLUSIONS: Holo-bLf, but not apo-bLf, delayed C. difficile growth and prevented toxin production in a human gut model of CDI. This inhibitory effect may be iron independent. These observations suggest that bLf in its iron-saturated state could be used as a novel preventative or treatment strategy for CDI. Oxford University Press 2016-04 2016-01-11 /pmc/articles/PMC4790624/ /pubmed/26759363 http://dx.doi.org/10.1093/jac/dkv452 Text en © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Chilton, C. H.
Crowther, G. S.
Śpiewak, K.
Brindell, M.
Singh, G.
Wilcox, M. H.
Monaghan, T. M.
Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection
title Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection
title_full Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection
title_fullStr Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection
title_full_unstemmed Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection
title_short Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection
title_sort potential of lactoferrin to prevent antibiotic-induced clostridium difficile infection
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790624/
https://www.ncbi.nlm.nih.gov/pubmed/26759363
http://dx.doi.org/10.1093/jac/dkv452
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