title: Microbiota-derived hydrogen fuels Salmonella typhimurium invasion of the gut ecosystem.
abstract: The intestinal microbiota features intricate metabolic interactions involving the breakdown and reuse of host- and diet-derived nutrients. The competition for these resources can limit pathogen growth. Nevertheless, some enteropathogenic bacteria can invade this niche through mechanisms that remain largely unclear. Using a mouse model for Salmonella diarrhea and a transposon mutant screen, we discovered that initial growth of Salmonella Typhimurium (S. Tm) in the unperturbed gut is powered by S. Tm hyb hydrogenase, which facilitates consumption of hydrogen (H2), a central intermediate of microbiota metabolism. In competitive infection experiments, a hyb mutant exhibited reduced growth early in infection compared to wild-type S. Tm, but these differences were lost upon antibiotic-mediated disruption of the host microbiota. Additionally, introducing H2-consuming bacteria into the microbiota interfered with hyb-dependent S. Tm growth. Thus, H2 is an Achilles' heel of microbiota metabolism that can be subverted by pathogens and might offer opportunities to prevent infection.
authors: Institute of Microbiology, ETH Zürich, CH-8093 Zurich, Switzerland.
authors: Lisa
authors: L
authors: Maier
authors: SIB Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Rounak
authors: R
authors: Vyas
authors: Institute of Microbiology, ETH Zürich, CH-8093 Zurich, Switzerland.
authors: Carmen Dolores
authors: CD
authors: Cordova
authors: SIB Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Helen
authors: H
authors: Lindsay
authors: SIB Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Thomas Sebastian Benedikt
authors: TS
authors: Schmidt
authors: Max-von-Pettenkofer Institute, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany.
authors: Sandrine
authors: S
authors: Brugiroux
authors: Institute of Microbiology, ETH Zürich, CH-8093 Zurich, Switzerland.
authors: Balamurugan
authors: B
authors: Periaswamy
authors: Institute of Microbiology, ETH Zürich, CH-8093 Zurich, Switzerland.
authors: Rebekka
authors: R
authors: Bauer
authors: Institute of Microbiology, ETH Zürich, CH-8093 Zurich, Switzerland.
authors: Alexander
authors: A
authors: Sturm
authors: Department of Environmental Microbiology, Eawag and Department of Environmental Systems Sciences, ETH Zurich, CH-8600 Dübendorf, Switzerland.
authors: Frank
authors: F
authors: Schreiber
authors: SIB Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Christian
authors: C
authors: von Mering
authors: SIB Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Mark D
authors: MD
authors: Robinson
authors: Max-von-Pettenkofer Institute, Ludwig-Maximilians-Universität Munich, 80336 Munich, Germany.
authors: Bärbel
authors: B
authors: Stecher
authors: Institute of Microbiology, ETH Zürich, CH-8093 Zurich, Switzerland. Electronic address: wolf-dietrich.hardt@micro.biol.ethz.ch.
authors: Wolf-Dietrich
authors: WD
authors: Hardt
mesh_terms: D000818:Animals; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006859:Hydrogen / Q000378:metabolism*; D006864:Hydrogenase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016254:Mutagenesis, Insertional; D012481:Salmonella Infections, Animal / Q000382:microbiology; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D006859:Hydrogen; D006864:Hydrogenase