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Fucose sensing regulates bacterial intestinal colonization

Abstract

The mammalian gastrointestinal tract provides a complex and competitive environment for the microbiota1. Successful colonization by pathogens requires scavenging nutrients, sensing chemical signals, competing with the resident bacteria and precisely regulating the expression of virulence genes2. The gastrointestinal pathogen enterohaemorrhagic Escherichia coli (EHEC) relies on inter-kingdom chemical sensing systems to regulate virulence gene expression3,4. 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 intestine5. Bacteroides thetaiotaomicron produces multiple fucosidases that cleave fucose from host glycans, resulting in high fucose availability in the gut lumen6. 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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Figure 1: The two-component system FusKR of EHEC.
Figure 2: z0462/z0463 regulates LEE expression.
Figure 3: Z0462 and Z0463 is a fucose-sensing two-component system.
Figure 4: FusK in pathogen–microbiota–host associations.

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Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

Microarray data are deposited in the Gene Expression Omnibus under accession number GSE34991.

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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 Grant 5 T32 AI7520-14. The contents are solely the responsibility of the authors and do not represent the official views of the NIH NIAID.

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A.R.P. led the project and performed experiments, designed experiments and wrote the paper. M.M.C. J.M.R., D.M., M.K.W. and C.G.M. helped with some experiments. V.S. designed experiments and wrote the paper.

Corresponding author

Correspondence to Vanessa Sperandio.

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The authors declare no competing financial interests.

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Pacheco, A., Curtis, M., Ritchie, J. et al. Fucose sensing regulates bacterial intestinal colonization. Nature 492, 113–117 (2012). https://doi.org/10.1038/nature11623

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