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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Autores principales:	Susan Hromada, Yili Qian, Tyler B Jacobson, Ryan L Clark, Lauren Watson, Nasia Safdar, Daniel Amador‐Noguez, Ophelia S Venturelli
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Clostridioides difficile computational modeling ecological interactions pathogen invasion systems biology Biology (General) QH301-705.5 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bd5ffbd93c85490aaac50f95aedc4ea4
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spelling	oai:doaj.org-article:bd5ffbd93c85490aaac50f95aedc4ea42021-11-11T11:30:48ZNegative interactions determine Clostridioides difficile growth in synthetic human gut communities1744-429210.15252/msb.202110355https://doaj.org/article/bd5ffbd93c85490aaac50f95aedc4ea42021-10-01T00:00:00Zhttps://doi.org/10.15252/msb.202110355https://doaj.org/toc/1744-4292Abstract 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.Susan HromadaYili QianTyler B JacobsonRyan L ClarkLauren WatsonNasia SafdarDaniel Amador‐NoguezOphelia S VenturelliWileyarticleClostridioides difficilecomputational modelingecological interactionspathogen invasionsystems biologyBiology (General)QH301-705.5Medicine (General)R5-920ENMolecular Systems Biology, Vol 17, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridioides difficile computational modeling ecological interactions pathogen invasion systems biology Biology (General) QH301-705.5 Medicine (General) R5-920
spellingShingle	Clostridioides difficile computational modeling ecological interactions pathogen invasion systems biology Biology (General) QH301-705.5 Medicine (General) R5-920 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
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
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
title	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_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_sort	negative interactions determine clostridioides difficile growth in synthetic human gut communities
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/bd5ffbd93c85490aaac50f95aedc4ea4
work_keys_str_mv	AT susanhromada negativeinteractionsdetermineclostridioidesdifficilegrowthinsynthetichumangutcommunities AT yiliqian negativeinteractionsdetermineclostridioidesdifficilegrowthinsynthetichumangutcommunities AT tylerbjacobson negativeinteractionsdetermineclostridioidesdifficilegrowthinsynthetichumangutcommunities AT ryanlclark negativeinteractionsdetermineclostridioidesdifficilegrowthinsynthetichumangutcommunities AT laurenwatson negativeinteractionsdetermineclostridioidesdifficilegrowthinsynthetichumangutcommunities AT nasiasafdar negativeinteractionsdetermineclostridioidesdifficilegrowthinsynthetichumangutcommunities AT danielamadornoguez negativeinteractionsdetermineclostridioidesdifficilegrowthinsynthetichumangutcommunities AT opheliasventurelli negativeinteractionsdetermineclostridioidesdifficilegrowthinsynthetichumangutcommunities
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Negative interactions determine Clostridioides difficile growth in synthetic human gut communities

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