Citrobacter rodentium Subverts ATP Flux and Cholesterol Homeostasis in Intestinal Epithelial Cells In Vivo.
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Date
2017-11-07Author
Berger, CN
Crepin, VF
Roumeliotis, TI
Wright, JC
Carson, D
Pevsner-Fischer, M
Furniss, RCD
Dougan, G
Dori-Bachash, M
Yu, L
Clements, A
Collins, JW
Elinav, E
Larrouy-Maumus, GJ
Choudhary, JS
Frankel, G
Type
Journal Article
Metadata
Show full item recordAbstract
The intestinal epithelial cells (IECs) that line the gut form a robust line of defense against ingested pathogens. We investigated the impact of infection with the enteric pathogen Citrobacter rodentium on mouse IEC metabolism using global proteomic and targeted metabolomics and lipidomics. The major signatures of the infection were upregulation of the sugar transporter Sglt4, aerobic glycolysis, and production of phosphocreatine, which mobilizes cytosolic energy. In contrast, biogenesis of mitochondrial cardiolipins, essential for ATP production, was inhibited, which coincided with increased levels of mucosal O2 and a reduction in colon-associated anaerobic commensals. In addition, IECs responded to infection by activating Srebp2 and the cholesterol biosynthetic pathway. Unexpectedly, infected IECs also upregulated the cholesterol efflux proteins AbcA1, AbcG8, and ApoA1, resulting in higher levels of fecal cholesterol and a bloom of Proteobacteria. These results suggest that C. rodentium manipulates host metabolism to evade innate immune responses and establish a favorable gut ecosystem.
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Subject
Intestinal Mucosa
Cell Line
Mitochondria
Epithelial Cells
Feces
Animals
Mice, Inbred C3H
Mice, Inbred C57BL
Humans
Mice
Citrobacter rodentium
Cholesterol
Adenosine Triphosphate
Proteomics
Female
Male
Immunity, Innate
Metabolomics
Research team
Functional Proteomics Group
Language
eng
Date accepted
2017-09-06
License start date
2017-11
Citation
Cell metabolism, 2017, 26 (5), pp. 738 - 752.e6
Publisher
CELL PRESS