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

Brugiroux, Sandrine; Beutler, Markus; Pfann, Carina; Garzetti, Debora; Ruscheweyh, Hans-Joachim; Ring, Diana; Diehl, Manuel; Herp, Simone; Lötscher, Yvonne; Hussain, Saib; Bunk, Boyke; Pukall, Rüdiger; Huson, Daniel H; Münch, Philipp C; McHardy, Alice C; McCoy, Kathleen; Macpherson, Andrew; Loy, Alexander; Clavel, Thomas; Berry, David; ... (2016). Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium. Nature Microbiology, 2, p. 16215. Nature Publishing Group 10.1038/nmicrobiol.2016.215

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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-MM(12)), 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-MM(12). 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

McCoy, Kathleen and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2058-5276

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

03 May 2017 10:07

Last Modified:

07 May 2017 02:23

Publisher DOI:

10.1038/nmicrobiol.2016.215

PubMed ID:

27869789

BORIS DOI:

10.7892/boris.94419

URI:

https://boris.unibe.ch/id/eprint/94419

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