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© Bruno Dupuy, Claire Morvan, Institut Pasteur
Cellules végétative et spores de Clostridioides difficile / Vegative cells and spores of Clostridioides difficile
News

Highlighted publication: “In vivo commensal control of Clostridioides difficile virulence” Girinathan et al., Cell Host & Microbes, Pathenogenesis of Bacterial Anaerobes team

In this collaborative paper, the Team “Pathenogenesis of Microbial Anaerobes” led by Bruno Dupuy illustrates how metabolically distinct species of Clostridia protect against or worsen Clostridioides difficile infection in mice by modulating the pathogen’s colonization, growth, and virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenter Paraclostridium bifermentans survive infection with reduced disease severity, while mice colonized with the butyrate-producer, Clostridium sardiniense, succumb more rapidly. Systematic in vivo analyses revealed how each commensal alters the gut-nutrient environment to modulate the pathogen’s metabolism, gene reg- ulatory networks, and toxin production. Oral administration of P. bifermentans rescues conventional, clinda- mycin-treated mice from lethal C. difficile infection in a manner similar to that of monocolonized animals, thereby supporting the therapeutic potential of this commensal species.

Those findings lay the foundation for mechanistically informed therapies to counter  disease using systems biology approaches to define host-commensal-pathogen interactions in vivo.

In vivo commensal control of Clostridioides difficile virulence

Cell Host & Microbe Vol. 29 Issue 11p1693–1708.e7 Published online: October 11, 2021

Brintha P. Girinathan, Nicholas DiBenedetto, Jay N. Worley, Johann Peltier, Mario L. Arrieta-Ortiz, Selva Rupa Christinal Immanuel, Richard Lavin, Mary L. Delaney, Christopher K. Cummins, Maria Hoffman, Yan Luo, Narjol Gonzalez-Escalona, Marc Allard, Andrew B. Onderdonk, Georg K. Gerber, Abraham L. Sonenshein, Nitin S. Baliga, Bruno Dupuy, and Lynn Bry

https://doi.org/10.1016/j.chom.2021.09.007