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Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration.

Lopez CA, Miller BM, Rivera-Chávez F, Velazquez EM, Byndloss MX, Chávez-Arroyo A, Lokken KL, Tsolis RM, Winter SE, Bäumler AJ
Science. 2016 353 (6305): 1249-53

PMID: 27634526 · PMCID: PMC5127919 · DOI:10.1126/science.aag3042

Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonic crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown mechanism. Here, we show that by triggering colonic crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygenation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the γ-secretase inhibitor dibenzazepine to diminish Notch-driven colonic crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C. rodentium infection. We conclude that C. rodentium uses its T3SS to induce histopathological lesions that generate an intestinal microenvironment in which growth of the pathogen is fueled by aerobic respiration.

Copyright © 2016, American Association for the Advancement of Science.

MeSH Terms (21)

Aerobiosis Amyloid Precursor Protein Secretases Animals Citrobacter rodentium Colitis Colon Cytochromes Dibenzazepines Electron Transport Chain Complex Proteins Enterobacteriaceae Infections Gene Deletion Hyperplasia Intestinal Mucosa Ki-67 Antigen Mice Mice, Inbred C3H Mice, Inbred C57BL Nitrates Oxidoreductases Receptors, Notch Virulence Factors

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