Food for thought—The link between Clostridioides difficile metabolism and pathogenesis
Clostridioides difficile (C. difficile) is an opportunistic pathogen that leads to antibiotic-associated diarrhoea and is a leading cause of morbidity and mortality worldwide. Antibiotic usage is the main risk factor leading to C. difficile infection (CDI), as a dysbiotic gut environment allows colo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815643/?tool=EBI |
| _version_ | 1797959161872384000 |
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| author | Andrew Marshall John W. McGrath Robert Graham Geoff McMullan |
| author_facet | Andrew Marshall John W. McGrath Robert Graham Geoff McMullan |
| author_sort | Andrew Marshall |
| collection | DOAJ |
| description | Clostridioides difficile (C. difficile) is an opportunistic pathogen that leads to antibiotic-associated diarrhoea and is a leading cause of morbidity and mortality worldwide. Antibiotic usage is the main risk factor leading to C. difficile infection (CDI), as a dysbiotic gut environment allows colonisation and eventual pathology manifested by toxin production. Although colonisation resistance is mediated by the action of secondary bile acids inhibiting vegetative outgrowth, nutrient competition also plays a role in preventing CDI as the gut microbiota compete for nutrient niches inhibiting C. difficile growth. C. difficile is able to metabolise carbon dioxide, the amino acids proline, hydroxyproline, and ornithine, the cell membrane constituent ethanolamine, and the carbohydrates trehalose, cellobiose, sorbitol, and mucin degradation products as carbon and energy sources through multiple pathways. Zinc sequestration by the host response mediates metabolic adaptation of C. difficile by perhaps signalling an inflamed gut allowing it to acquire abundant nutrients. Persistence within the gut environment is also mediated by the by-products of metabolism through the production of p-cresol, which inhibit gut commensal species growth promoting dysbiosis. This review aims to explore and describe the various metabolic pathways of C. difficile, which facilitate its survival and pathogenesis within the colonised host gut. Author summary Clostridioides difficile (C. difficile) infection (CDI) is a global health threat being the leading cause of antibiotic-associated diarrhoea. CDI is mediated by the toxins TcdA and TcdB, which act to damage the gut epithelium leading to a breakdown in the gut barrier integrity. In addition, CDI possesses a high recurrence rate, owing to the ability of C. difficile to produce highly resilient endospores allowing it to persist following antibiotic treatment regimes. The ability of a pathogen to successfully colonise the gut relies on its ability to acquire and metabolise nutrients from its environment. C. difficile is proposed to act as a bacterial generalist, capitalising on the broad range of available nutrients present within a dysbiotic gut environment. This review describes the metabolic capabilities of C. difficile within the current literature to provide an overview of the genetic and molecular basis in which its metabolism operates following gut colonisation and how this contributes towards pathogenicity. |
| first_indexed | 2024-04-11T00:29:34Z |
| format | Article |
| id | doaj.art-7c584a74fe7742e19cf45f0c8e05c49c |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-11T00:29:34Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-7c584a74fe7742e19cf45f0c8e05c49c2023-01-08T05:30:57ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-01-01191Food for thought—The link between Clostridioides difficile metabolism and pathogenesisAndrew MarshallJohn W. McGrathRobert GrahamGeoff McMullanClostridioides difficile (C. difficile) is an opportunistic pathogen that leads to antibiotic-associated diarrhoea and is a leading cause of morbidity and mortality worldwide. Antibiotic usage is the main risk factor leading to C. difficile infection (CDI), as a dysbiotic gut environment allows colonisation and eventual pathology manifested by toxin production. Although colonisation resistance is mediated by the action of secondary bile acids inhibiting vegetative outgrowth, nutrient competition also plays a role in preventing CDI as the gut microbiota compete for nutrient niches inhibiting C. difficile growth. C. difficile is able to metabolise carbon dioxide, the amino acids proline, hydroxyproline, and ornithine, the cell membrane constituent ethanolamine, and the carbohydrates trehalose, cellobiose, sorbitol, and mucin degradation products as carbon and energy sources through multiple pathways. Zinc sequestration by the host response mediates metabolic adaptation of C. difficile by perhaps signalling an inflamed gut allowing it to acquire abundant nutrients. Persistence within the gut environment is also mediated by the by-products of metabolism through the production of p-cresol, which inhibit gut commensal species growth promoting dysbiosis. This review aims to explore and describe the various metabolic pathways of C. difficile, which facilitate its survival and pathogenesis within the colonised host gut. Author summary Clostridioides difficile (C. difficile) infection (CDI) is a global health threat being the leading cause of antibiotic-associated diarrhoea. CDI is mediated by the toxins TcdA and TcdB, which act to damage the gut epithelium leading to a breakdown in the gut barrier integrity. In addition, CDI possesses a high recurrence rate, owing to the ability of C. difficile to produce highly resilient endospores allowing it to persist following antibiotic treatment regimes. The ability of a pathogen to successfully colonise the gut relies on its ability to acquire and metabolise nutrients from its environment. C. difficile is proposed to act as a bacterial generalist, capitalising on the broad range of available nutrients present within a dysbiotic gut environment. This review describes the metabolic capabilities of C. difficile within the current literature to provide an overview of the genetic and molecular basis in which its metabolism operates following gut colonisation and how this contributes towards pathogenicity.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815643/?tool=EBI |
| spellingShingle | Andrew Marshall John W. McGrath Robert Graham Geoff McMullan Food for thought—The link between Clostridioides difficile metabolism and pathogenesis PLoS Pathogens |
| title | Food for thought—The link between Clostridioides difficile metabolism and pathogenesis |
| title_full | Food for thought—The link between Clostridioides difficile metabolism and pathogenesis |
| title_fullStr | Food for thought—The link between Clostridioides difficile metabolism and pathogenesis |
| title_full_unstemmed | Food for thought—The link between Clostridioides difficile metabolism and pathogenesis |
| title_short | Food for thought—The link between Clostridioides difficile metabolism and pathogenesis |
| title_sort | food for thought the link between clostridioides difficile metabolism and pathogenesis |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815643/?tool=EBI |
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