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© Bruno Dupuy, Claire Morvan, Institut Pasteur
Cellules végétative et spores de Clostridioides difficile / Vegative cells and spores of Clostridioides difficile
Publication : Cell host & microbe

Predictive regulatory and metabolic network models for systems analysis of Clostridioides difficile.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell host & microbe - 10 Nov 2021

Arrieta-Ortiz ML, Immanuel SRC, Turkarslan S, Wu WJ, Girinathan BP, Worley JN, DiBenedetto N, Soutourina O, Peltier J, Dupuy B, Bry L, Baliga NS

Link to Pubmed [PMID] – 34637780

Link to DOI – 10.1016/j.chom.2021.09.008

Cell Host Microbe 2021 Nov; 29(11): 1709-1723.e5

We present predictive models for comprehensive systems analysis of Clostridioides difficile, the etiology of pseudomembranous colitis. By leveraging 151 published transcriptomes, we generated an EGRIN model that organizes 90% of C. difficile genes into a transcriptional regulatory network of 297 co-regulated modules, implicating genes in sporulation, carbohydrate transport, and metabolism. By advancing a metabolic model through addition and curation of metabolic reactions including nutrient uptake, we discovered 14 amino acids, diverse carbohydrates, and 10 metabolic genes as essential for C. difficile growth in the intestinal environment. Finally, we developed a PRIME model to uncover how EGRIN-inferred combinatorial gene regulation by transcription factors, such as CcpA and CodY, modulates essential metabolic processes to enable C. difficile growth relative to commensal colonization. The C. difficile interactive web portal provides access to these model resources to support collaborative systems-level studies of context-specific virulence mechanisms in C. difficile.