Header

UZH-Logo

Maintenance Infos

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


Kentner, David; Martano, Giuseppe; Callon, Morgane; Chiquet, Petra; Brodmann, Maj; Burton, Olga; Wahlander, Asa; Nanni, Paolo; Delmotte, Nathanaël; Grossmann, Jonas; Limenitakis, Julien; Schlapbach, Ralph; Kiefer, Patrick; Vorholt, Julia A; Hiller, Sebastian; 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):9929-9934.

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.

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.

Statistics

Citations

19 citations in Web of Science®
19 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

20 downloads since deposited on 29 Jan 2015
12 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:8 July 2014
Deposited On:29 Jan 2015 11:43
Last Modified:08 Dec 2017 11:30
Publisher:National Academy of Sciences
ISSN:0027-8424
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1073/pnas.1406694111
PubMed ID:24958876

Download

Download PDF  'Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth'.
Preview
Filetype: PDF
Size: 945kB
View at publisher