Negative interactions determine Clostridioides difficile growth in synthetic human gut communities.

Autor: Hromada S; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, USA., Qian Y; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA., Jacobson TB; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA., Clark RL; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA., Watson L; Division of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.; Department of Medicine, William S. Middleton Veterans Hospital Madison, Madison, WI, USA., Safdar N; Division of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.; Department of Medicine, William S. Middleton Veterans Hospital Madison, Madison, WI, USA., Amador-Noguez D; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA., Venturelli OS; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2021 Oct; Vol. 17 (10), pp. e10355.
DOI: 10.15252/msb.202110355
Abstrakt: 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.
(© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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