Fucose sensing regulates bacterial intestinal colonization

• Published in: Nature (London) Vol. 492; no. 7427; pp. 113 - 117
• Main Authors: Pacheco, Alline R., Curtis, Meredith M., Ritchie, Jennifer M., Munera, Diana, Waldor, Matthew K., Moreira, Cristiano G., Sperandio, Vanessa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.12.2012; Nature Publishing Group
• Subjects: 631/208/200; 631/326/41/1969; 631/326/41/2531; 631/80/86; alpha-L-Fucosidase - metabolism; Animal, plant and microbial ecology; Animals; Bacterial Proteins - metabolism; Bacteriology; Bacteroides - enzymology; Bacteroides - growth & development; Bacteroides - metabolism; Biological and medical sciences; Cellular signal transduction; Colonization; Competition; Drug therapy; E coli; Enterohemorrhagic Escherichia coli - genetics; Enterohemorrhagic Escherichia coli - growth & development; Enterohemorrhagic Escherichia coli - pathogenicity; Escherichia coli; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Fucose - metabolism; Fundamental and applied biological sciences. Psychology; Gastrointestinal diseases; Gastrointestinal system; Gastrointestinal tract; Gastrointestinal Tract - metabolism; Gastrointestinal Tract - microbiology; Gene expression; Gene Expression Regulation, Bacterial; Genetic aspects; Health aspects; Histidine; Humanities and Social Sciences; Kinases; letter; Mammals; Microbial ecology; Microbiology; Microbiota (Symbiotic organisms); Mucins - metabolism; multidisciplinary; Normal microflora of man and animals. Rumen; Pathogens; Physiological aspects; Protein Kinases - genetics; Protein Kinases - metabolism; Rabbits; Receptors, Adrenergic - metabolism; Resveratrol; Risk factors; Science; Signal Transduction; Transcription Factors - genetics; Transcription Factors - metabolism; Virulence - genetics; Virulence Factors - genetics; United States; Animal microorganism relation; Escherichia coli; Virulence; Gut; Signal transduction; Vertebrata; Mammalia; Pathogenic; Bacteria; Associated microflora; Microbial community; Enterobacteriaceae; Fucose
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature11623

FusKR, a fucose-sensing two-component system, has been identified in enterohaemorrhagic E. coli , linking fucose utilization and virulence factor gene expression and providing insight into how sensing of a host signal can facilitate bacterial colonization. Control of intestinal microbiota Enterohaemorrhagic Escherichia coli (EHEC) possess a number of virulence factors that promote colonization of the mammalian gut. This study describes the discovery of a new regulatory twist in virulence-factor expression by EHEC. A novel two-component system is shown to sense fucose and regulate both fucose utilization and virulence-factor gene expression. Fucose is liberated from host glycans by members of the resident microbiota, so these findings highlight a complex interplay between the host, microbiota and invading pathogens. The mammalian gastrointestinal tract provides a complex and competitive environment for the microbiota 1 . Successful colonization by pathogens requires scavenging nutrients, sensing chemical signals, competing with the resident bacteria and precisely regulating the expression of virulence genes 2 . The gastrointestinal pathogen enterohaemorrhagic Escherichia coli (EHEC) relies on inter-kingdom chemical sensing systems to regulate virulence gene expression 3 , 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 intestine 5 . Bacteroides thetaiotaomicron produces multiple fucosidases that cleave fucose from host glycans, resulting in high fucose availability in the gut lumen 6 . 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.