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Nat Microbiol. 2016 Nov 21;2:16215. doi: 10.1038/nmicrobiol.2016.215.

Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium.

Author information

1
Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
2
Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network Chemistry meets Microbiology, University of Vienna, A-1090 Vienna, Austria.
3
German Center for Infection Research (DZIF); Partner Site Munich.
4
Center for Bioinformatics, University of Tübingen, 72076 Tübingen, Germany.
5
Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
6
DSMZ - German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany.
7
Computational Biology of Infection Research, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
8
Department of Algorithmic Bioinformatics, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
9
Maurice Müller Laboratories, Department of Clinical Research (DKF), UVCM, University Hospital, 3010 Bern, Switzerland.
10
ZIEL Institute for Food and Health, Technische Universität München, 85354 Freising, Germany.

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.

PMID:
27869789
DOI:
10.1038/nmicrobiol.2016.215
[Indexed for MEDLINE]

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