Negative Interactions Determine Clostridioides Difficile Growth in Synthetic Human Gut Communities

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2021 Oct 25

PMID 34693621

Citations 24

Authors

Susan Hromada

Yili Qian

Tyler B Jacobson

Ryan L Clark

Lauren Watson

Nasia Safdar

Daniel Amador-Noguez

Ophelia S Venturelli

Affiliations

Soon will be listed here.

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.

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