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Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth

Kentner, David and Martano, Giuseppe and Callon, Morgane and Chiquet, Petra and Brodmann, Maj and Burton, Olga and Wahlander, Asa and Nanni, Paolo and Delmotte, Nathanaël and Grossmann, Jonas and Limenitakis, Julien and Schlapbach, Ralph and Kiefer, Patrick and Vorholt, Julia A. and Hiller, Sebastian and Bumann, Dirk. (2014) Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth. Proceedings of the National Academy of Sciences of the United States of America, 111 (27). pp. 9929-9934.

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Official URL: http://edoc.unibas.ch/dok/A6271985

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Abstract

Shigella flexneri proliferate in infected human epithelial cells at exceptionally high rates. This vigorous growth has important consequences for rapid progression to life-threatening bloody diarrhea, but the underlying metabolic mechanisms remain poorly understood. Here, we used metabolomics, proteomics, and genetic experiments to determine host and Shigella metabolism during infection in a cell culture model. The data suggest that infected host cells maintain largely normal fluxes through glycolytic pathways, but the entire output of these pathways is captured by Shigella, most likely in the form of pyruvate. This striking strategy provides Shigella with an abundant favorable energy source, while preserving host cell ATP generation, energy charge maintenance, and survival, despite ongoing vigorous exploitation. Shigella uses a simple three-step pathway to metabolize pyruvate at high rates with acetate as an excreted waste product. The crucial role of this pathway for Shigella intracellular growth suggests targets for antimicrobial chemotherapy of this devastating disease.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann)
UniBasel Contributors:Bumann, Dirk and Callon, Morgane and Hiller Odermatt, Sebastian
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
e-ISSN:1091-6490
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Dec 2017 13:24
Deposited On:10 Oct 2014 09:19

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