TY - JOUR
T1 - Fucose sensing regulates bacterial intestinal colonization
AU - Pacheco, Alline R.
AU - Curtis, Meredith M.
AU - Ritchie, Jennifer M.
AU - Munera, Diana
AU - Waldor, Matthew K.
AU - Moreira, Cristiano G.
AU - Sperandio, Vanessa
N1 - Funding Information:
Acknowledgements We thank M. Kendall for comments. We thank the microarray core facility. This work was supported by the National Institutes of Health (NIH) Grants AI053067, AI77853 and AI077613, and the Burroughs Wellcome Fund (to V.S.) and NIH Grant AI42347 and HHMI (to M.K.W.). M.M.C. was supported through NIH Training Grant5 T32 AI7520-14. The contents are solely the responsibility of the authors anddo not represent the official views of the NIH NIAID.
PY - 2012/12/6
Y1 - 2012/12/6
N2 - The mammalian gastrointestinal tract provides a complex and competitive environment for the microbiota. Successful colonization by pathogens requires scavenging nutrients, sensing chemical signals, competing with the resident bacteria and precisely regulating the expression of virulence genes. The gastrointestinal pathogen enterohaemorrhagic Escherichia coli (EHEC) relies on inter-kingdom chemical sensing systems to regulate virulence gene expression. Here we show that these systems control the expression of a novel two-component signal transduction system, named FusKR, where FusK is the histidine sensor kinase and FusR the response regulator. FusK senses fucose and controls expression of virulence and metabolic genes. This fucose-sensing system is required for robust EHEC colonization of the mammalian intestine. Fucose is highly abundant in the intestine. Bacteroides thetaiotaomicron produces multiple fucosidases that cleave fucose from host glycans, resulting in high fucose availability in the gut lumen. During growth in mucin, B. thetaiotaomicron contributes to EHEC virulence by cleaving fucose from mucin, thereby activating the FusKR signalling cascade, modulating the virulence gene expression of EHEC. Our findings suggest that EHEC uses fucose, a host-derived signal made available by the microbiota, to modulate EHEC pathogenicity and metabolism.
AB - The mammalian gastrointestinal tract provides a complex and competitive environment for the microbiota. Successful colonization by pathogens requires scavenging nutrients, sensing chemical signals, competing with the resident bacteria and precisely regulating the expression of virulence genes. The gastrointestinal pathogen enterohaemorrhagic Escherichia coli (EHEC) relies on inter-kingdom chemical sensing systems to regulate virulence gene expression. Here we show that these systems control the expression of a novel two-component signal transduction system, named FusKR, where FusK is the histidine sensor kinase and FusR the response regulator. FusK senses fucose and controls expression of virulence and metabolic genes. This fucose-sensing system is required for robust EHEC colonization of the mammalian intestine. Fucose is highly abundant in the intestine. Bacteroides thetaiotaomicron produces multiple fucosidases that cleave fucose from host glycans, resulting in high fucose availability in the gut lumen. During growth in mucin, B. thetaiotaomicron contributes to EHEC virulence by cleaving fucose from mucin, thereby activating the FusKR signalling cascade, modulating the virulence gene expression of EHEC. Our findings suggest that EHEC uses fucose, a host-derived signal made available by the microbiota, to modulate EHEC pathogenicity and metabolism.
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U2 - 10.1038/nature11623
DO - 10.1038/nature11623
M3 - Letter
C2 - 23160491
AN - SCOPUS:84870501494
SN - 0028-0836
VL - 492
SP - 113
EP - 117
JO - Nature
JF - Nature
IS - 7427
ER -