Editors' ChoiceMicrobiology

Bacterial Cooperation

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Science Signaling  11 Dec 2012:
Vol. 5, Issue 254, pp. ec314
DOI: 10.1126/scisignal.2003861

Trillions of commensal bacteria live in the human gastrointestinal tract, so pathogenic bacteria experience extreme competition for resources. Pacheco et al. found that the commensal bacterium Bacteroides thetaiotaomicron, which grows in intestinal mucin, produced fucose that the pathogenic bacterium enterohaemorrhagic Escherichia coli (EHEC) used to regulate its metabolism and effectively compete for nutrients in order to successfully colonize the intestinal epithelium. The locus of enterocyte effacement (LEE) is an EHEC pathogenicity locus encoding its own transcriptional regulator, Ler, and a type III secretion system, and its expression is stimulated by host adrenergic hormones and by the microbial product autoinducer-3. However, induction of this locus is energetically expensive for the bacteria. The two-component systems that activate LEE also repressed z0462 and z0463, which encode a putative histidine kinase with homology to sugar sensors and a response regulator (a transcription factor regulated by a histidine kinase), respectively, thus comprising a putative two-component system. Transcriptional analysis of EHEC lacking either of these genes indicated that the system primarily functioned to repress transcription of target genes, including ler, which encodes the transcriptional regulator that stimulates LEE, and the fuc genes, which encode proteins needed for fucose metabolism. Expression of z0463 was increased in EHEC cultured with intestinal cells that produced mucus, which contains polymers of fucose, compared with those that did not. Liposomes containing z0462 exhibited autophosphorylation in response to fucose, but not glucose or ribose, indicating that z0462 was a fucose sensor, and thus was named FusK, and z0463 was named FusR as the fucose-sensing response regulator. Bacteria lacking fusK failed to repress ler in response to fucose, and repression of ler in wild-type bacteria was promoted by culturing the bacteria with B. thetaiotaomicron to degrade the mucin and release fucose. In vitro competition assays indicated that the ability of FusK-deficient bacteria to use fucose, which could confer a growth advantage in fucose, was countered by the overexpression of LEE, which is energetically expensive, because FusK-deficient bacteria did not have a growth advantage over wild-type bacteria when cultured in fucose-containing medium. When cultured in mucin in the absence of B. thetaiotaomicron, the wild-type bacteria had a growth advantage over the FusK-deficient cells that was negated by growth in the presence of mucin and B. thetaiotaomicron. In vivo competition assays in infant rabbits also showed that the wild-type bacteria that could sense and respond to fucose were more effective at gut colonization than were the FusK-deficient bacteria. A double mutant that could not respond to fucose and could not activate fuc genes was also outcompeted by wild-type bacteria in in vivo competition assays, suggesting that repression of LEE, not the ability to alter fucose metabolism, is the key to the competition. The authors propose that the FusK-FusR two-component system functions to repress the energy-expensive expression of LEE in the intestinal mucus layer, where the cells cannot infect the epithelium, and that once close to the epithelial surface, the response to the host adrenergic signal takes over, repressing FusK-FusR signaling and stimulating virulence through LEE.

A. R. Pacheco, M. M. Curtis, J. M. Ritchie, D. Munera, M. K. Waldor, C. G. Moreira, V. Sperandio, Fucose sensing regulates bacterial intestinal colonization. Nature 492, 113–117 (2012). [PubMed]

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