Imperial College London
Portrait Picture

ProfessorGadFrankel

Faculty of Natural Sciences, Department of Life Sciences

Professor of Molecular Pathogenesis
 
 
 
//

Contact

 

+44 (0)20 7594 5253g.frankel

 
 
//

Location

 

1.46Flowers buildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Carson:2020:10.1111/cmi.13126,
author = {Carson, D and Barry, R and Eve, GD H and Roumeliotis, T and García-Weber, D and Mullineaux, Sanders C and Elinav, E and Arrieumerlou, C and Choudhary, J and Frankel, G},
doi = {10.1111/cmi.13126},
journal = {Cellular Microbiology},
pages = {1--17},
title = {Citrobacter rodentium induces rapid and unique metabolic and inflammatory responses in mice suffering from severe disease},
url = {http://dx.doi.org/10.1111/cmi.13126},
volume = {22},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The mouse pathogen Citrobacter rodentium is used to model infections with enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC). Pathogenesis is commonly modelled in mice developing mild disease (e.g., C57BL/6). However, little is known about host responses in mice exhibiting severe colitis (e.g., C3H/HeN), which arguably provide a more clinically relevant model for human paediatric enteric infection. Infection of C3H/HeN mice with C. rodentium results in rapid colonic colonisation, coinciding with induction of key inflammatory signatures and colonic crypt hyperplasia. Infection also induces dramatic changes to bioenergetics in intestinal epithelial cells, with transition from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and higher abundance of SGLT4, LDHA, and MCT4. Concomitantly, mitochondrial proteins involved in the TCA cycle and OXPHOS were in lower abundance. Similar to observations in C57BL/6 mice, we detected simultaneous activation of cholesterol biogenesis, import, and efflux. Distinctly, however, the pattern recognition receptors NLRP3 and ALPK1 were specifically induced in C3H/HeN. Using cellbased assays revealed that C. rodentium activates the ALPK1/TIFA axis, which is dependent on the ADPheptose biosynthesis pathway but independent of the Type III secretion system. This study reveals for the first time the unfolding intestinal epithelial cells' responses during severe infectious colitis, which resemble EPEC human infections.
AU  - Carson,D
AU  - Barry,R
AU  - Eve,GD H
AU  - Roumeliotis,T
AU  - García-Weber,D
AU  - Mullineaux,Sanders C
AU  - Elinav,E
AU  - Arrieumerlou,C
AU  - Choudhary,J
AU  - Frankel,G
DO  - 10.1111/cmi.13126
EP  - 17
PY  - 2020///
SN  - 1462-5814
SP  - 1
TI  - Citrobacter rodentium induces rapid and unique metabolic and inflammatory responses in mice suffering from severe disease
T2  - Cellular Microbiology
UR  - http://dx.doi.org/10.1111/cmi.13126
UR  - https://onlinelibrary.wiley.com/doi/full/10.1111/cmi.13126
UR  - http://hdl.handle.net/10044/1/74359
VL  - 22
ER  -
Download