title: Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium.
abstract: Protection against enteric infections, also termed colonization resistance, results from mutualistic interactions of the host and its indigenous microbes. The gut microbiota of humans and mice is highly diverse and it is therefore challenging to assign specific properties to its individual members. Here, we have used a collection of murine bacterial strains and a modular design approach to create a minimal bacterial community that, once established in germ-free mice, provided colonization resistance against the human enteric pathogen Salmonella enterica serovar Typhimurium (S. Tm). Initially, a community of 12 strains, termed Oligo-Mouse-Microbiota (Oligo-MM12), representing members of the major bacterial phyla in the murine gut, was selected. This community was stable over consecutive mouse generations and provided colonization resistance against S. Tm infection, albeit not to the degree of a conventional complex microbiota. Comparative (meta)genome analyses identified functions represented in a conventional microbiome but absent from the Oligo-MM12. By genome-informed design, we created an improved version of the Oligo-MM community harbouring three facultative anaerobic bacteria from the mouse intestinal bacterial collection (miBC) that provided conventional-like colonization resistance. In conclusion, we have established a highly versatile experimental system that showed efficacy in an enteric infection model. Thus, in combination with exhaustive bacterial strain collections and systems-based approaches, genome-guided design can be used to generate insights into microbe-microbe and microbe-host interactions for the investigation of ecological and disease-relevant mechanisms in the intestine.
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Brugiroux
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Beutler
authors.affiliation: Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network Chemistry meets Microbiology, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Carina
authors.initials: C
authors.lastname: Pfann
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.|German Center for Infection Research (DZIF); Partner Site Munich.
authors.forename: Debora
authors.initials: D
authors.lastname: Garzetti
authors.affiliation: Center for Bioinformatics, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Ruscheweyh
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Ring
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Diehl
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Herp
authors.affiliation: Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lötscher
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
authors.forename: Saib
authors.initials: S
authors.lastname: Hussain
authors.affiliation: DSMZ - German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany.
authors.forename: Boyke
authors.initials: B
authors.lastname: Bunk
authors.affiliation: DSMZ - German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Pukall
authors.affiliation: Center for Bioinformatics, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Huson
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.|Computational Biology of Infection Research, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Philipp C
authors.initials: PC
authors.lastname: Münch
authors.affiliation: Computational Biology of Infection Research, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.|Department of Algorithmic Bioinformatics, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Alice C
authors.initials: AC
authors.lastname: McHardy
authors.affiliation: Maurice Müller Laboratories, Department of Clinical Research (DKF), UVCM, University Hospital, 3010 Bern, Switzerland.
authors.forename: Kathy D
authors.initials: KD
authors.lastname: McCoy
authors.affiliation: Maurice Müller Laboratories, Department of Clinical Research (DKF), UVCM, University Hospital, 3010 Bern, Switzerland.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Macpherson
authors.affiliation: Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network Chemistry meets Microbiology, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Alexander
authors.identifier: http://orcid.org/0000-0001-8923-5882
authors.initials: A
authors.lastname: Loy
authors.affiliation: ZIEL Institute for Food and Health, Technische Universität München, 85354 Freising, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Clavel
authors.affiliation: Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network Chemistry meets Microbiology, University of Vienna, A-1090 Vienna, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Berry
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.|German Center for Infection Research (DZIF); Partner Site Munich.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Stecher
mesh_terms: D000818:Animals; D000898:Antibiosis; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D051379:Mice; D012481:Salmonella Infections, Animal / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000502:physiology*