In vivo commensal control of Clostridioides difficile virulence.

Autor:	Girinathan BP; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., DiBenedetto N; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Worley JN; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; National Center of Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA., Peltier J; Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, UMR CNRS 2001, Université de Paris, 25-28 Rue du Dr. Roux, Institut Pasteur, 75015 Paris Cedex, France; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198, Gif-sur-yvette Cedex, France., Arrieta-Ortiz ML; Institute for Systems Biology, Seattle, WA 98109, USA., Immanuel SRC; Institute for Systems Biology, Seattle, WA 98109, USA., Lavin R; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Delaney ML; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Clinical Microbiology Laboratory, Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115, USA., Cummins CK; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Hoffman M; Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, Department of Microbiology, College Park, MD 20740, USA., Luo Y; Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, Department of Microbiology, College Park, MD 20740, USA., Gonzalez-Escalona N; Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, Department of Microbiology, College Park, MD 20740, USA., Allard M; Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, Department of Microbiology, College Park, MD 20740, USA., Onderdonk AB; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Clinical Microbiology Laboratory, Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115, USA., Gerber GK; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Health Sciences & Technology, Cambridge, MA 02139, USA., Sonenshein AL; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA., Baliga NS; Institute for Systems Biology, Seattle, WA 98109, USA., Dupuy B; Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, UMR CNRS 2001, Université de Paris, 25-28 Rue du Dr. Roux, Institut Pasteur, 75015 Paris Cedex, France., Bry L; Massachusetts Host-Microbiome Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Clinical Microbiology Laboratory, Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115, USA. Electronic address: lbry@bwh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Cell host & microbe [Cell Host Microbe] 2021 Nov 10; Vol. 29 (11), pp. 1693-1708.e7. Date of Electronic Publication: 2021 Oct 11.
DOI:	10.1016/j.chom.2021.09.007
Abstrakt:	Leveraging systems biology approaches, we illustrate 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 regulatory networks, and toxin production. Oral administration of P. bifermentans rescues conventional, clindamycin-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. Our findings lay the foundation for mechanistically informed therapies to counter C. difficile disease using systems biology approaches to define host-commensal-pathogen interactions in vivo. Competing Interests: Declaration of interests L.B. and G.K.G. are co-inventors on patents for C. difficile microbiota therapeutics. L.B., G.K.G., and A.L.S. are SAB members and hold stock in ParetoBio. G.K.G.is an SAB member and holds stock in Kaleido, Inc. A.L.S. is a co-owner of ExArca Pharmaceuticals. The remaining authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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