Negative interactions determine Clostridioides difficile growth in synthetic human gut communities
Abstract Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut micro...
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-10-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.202110355 |
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| author | Susan Hromada Yili Qian Tyler B Jacobson Ryan L Clark Lauren Watson Nasia Safdar Daniel Amador‐Noguez Ophelia S Venturelli |
| author_facet | Susan Hromada Yili Qian Tyler B Jacobson Ryan L Clark Lauren Watson Nasia Safdar Daniel Amador‐Noguez Ophelia S Venturelli |
| author_sort | Susan Hromada |
| collection | DOAJ |
| description | Abstract Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition. |
| format | Article |
| id | doaj-art-bd5ffbd93c85490aaac50f95aedc4ea4 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-bd5ffbd93c85490aaac50f95aedc4ea42025-08-20T03:42:04ZengSpringer NatureMolecular Systems Biology1744-42922021-10-01171011910.15252/msb.202110355Negative interactions determine Clostridioides difficile growth in synthetic human gut communitiesSusan Hromada0Yili Qian1Tyler B Jacobson2Ryan L Clark3Lauren Watson4Nasia Safdar5Daniel Amador‐Noguez6Ophelia S Venturelli7Department of Biochemistry, University of Wisconsin‐MadisonDepartment of Biochemistry, University of Wisconsin‐MadisonDepartment of Bacteriology, University of Wisconsin‐MadisonDepartment of Biochemistry, University of Wisconsin‐MadisonDivision of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin‐MadisonDivision of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin‐MadisonDepartment of Bacteriology, University of Wisconsin‐MadisonDepartment of Biochemistry, University of Wisconsin‐MadisonAbstract Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition.https://doi.org/10.15252/msb.202110355Clostridioides difficilecomputational modelingecological interactionspathogen invasionsystems biology |
| spellingShingle | Susan Hromada Yili Qian Tyler B Jacobson Ryan L Clark Lauren Watson Nasia Safdar Daniel Amador‐Noguez Ophelia S Venturelli Negative interactions determine Clostridioides difficile growth in synthetic human gut communities Molecular Systems Biology Clostridioides difficile computational modeling ecological interactions pathogen invasion systems biology |
| title | Negative interactions determine Clostridioides difficile growth in synthetic human gut communities |
| title_full | Negative interactions determine Clostridioides difficile growth in synthetic human gut communities |
| title_fullStr | Negative interactions determine Clostridioides difficile growth in synthetic human gut communities |
| title_full_unstemmed | Negative interactions determine Clostridioides difficile growth in synthetic human gut communities |
| title_short | Negative interactions determine Clostridioides difficile growth in synthetic human gut communities |
| title_sort | negative interactions determine clostridioides difficile growth in synthetic human gut communities |
| topic | Clostridioides difficile computational modeling ecological interactions pathogen invasion systems biology |
| url | https://doi.org/10.15252/msb.202110355 |
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