• Citation: Arrieta-Ortiz et al. 2020. bioRxiv. Predictive regulatory and metabolic network models for systems analysis of Clostridioides difficile

    Clostridioides difficile causes >500,000 infections, >30,000 deaths, and > $5 billion/year in US healthcare costs, and rates continue to rise. Antimicrobial therapy that ablates the commensal microbiota commonly triggers infection, allowing the pathogen to proliferate and release toxins that damage host mucosal surfaces. Resistance to commonly prescribed antibiotics occurs in >20% of patient isolates, a problem that confounds treatment and increases risks for recurrent infections. In this research program, we are building predictive and mechanistic models to define mechanisms by which C. difficile responds to antibiotics, host and microbiota-origin factors, and to develop therapeutic interventions to prevent colonization, infection and recurrence of C. difficile.

    The multi-institutional team from ISB, Brigham & Women’s Hospital (BWH), the Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur is interrogating the diverse capabilities of C. difficile by longitudinally profiling changes in its transcriptome, protein-DNA interactions, and phenotypes across dozens of environments and in vivo host-contexts. We are integrating these multi-omics datasets and generating systems-scale regulatory and metabolic network models to dissect conditionally active programs that control virulence (e.g., toxin production), colonization, and adaptive responses of C. difficile. These models and datasets will enable hypothesis-driven experimentation to characterize conditional vulnerabilities of C. difficile across diverse host-relevant contexts and enable rational formulation of effective therapy regimens.


Nitin S. Baliga, PhD. Professor, Senior Vice President and Director
Mario Arrieta-Ortiz Research Scientist
Serdar Turkarslan Senior Research Scientist
Selva Rupa C. Immanuel Postdoctoral Fellow
Lynn Bry, MD, PhD. Associate Professor of Pathology at Harvard Medical School and Associate Director of the Clinical Microbiology Laboratory at Brigham & Women's Hospital.
Mary Delaney
Vladimir Yeliseyev
Jay Worley
Brintha Girinathan
Nick DiBenedetto
Olivia Trofimuk
Qing Liu
Kit Cummins
Bruno Dupuy, PhD. the head of the Pathogenesis of Bacterial Anaerobes laboratory at the Institut Pasteur.
Claire MORVAN Permanent Researcher