. Here, we show that whereas NanR, a sialic acid-response regulator, binds to region 1, NagC, a GlcNAc-6P-responsive protein, binds to region 2 instead. The NanR-and NagC-binding sites lie adjacent to deoxyadenosine methylase (Dam) methylation sites (5 -GATC) that are protected from modification, and the two regulators are shown to be required for methylation protection at regions 1 and 2, respectively. Mutations in nanR and nagC diminish fimB expression, and both fimB expression and FimB recombination are inhibited by GlcNAc (3-and >35-fold, respectively). Sialic acid catabolism generates GlcNAc-6-P, and whereas GlcNAc disrupts methylation protection by NagC alone, Neu5Ac inhibits the protection mediated by both NanR and NagC as expected. Type 1 fimbriae are proinflammatory, and host defenses enhance the release of both Neu5Ac and GlcNAc by a variety of mechanisms. Inhibition of type 1 fimbriation by these amino sugars may thus help balance the interaction between E. coli and its hosts. type 1 fimbriae

SummaryThe phase variation of type 1 fimbriation in Escherichia coli is controlled by the inversion of a 314 bp element of DNA, determined by FimB (switching in both directions) or FimE (switching from the ON-to-OFF orientation predominantly), and influenced by auxiliary factors IHF, Lrp and H-NS. The fimB gene is separated from the divergently transcribed yjhATS operon by a large (1.4 kbp) intergenic region of unknown function. Here, we show that fimB expression is regulated by multiple cis-active sequences that lie far upstream ( > 600 bp) of the transcription start sites for the recombinase gene. Two regions characterized further (regions 1 and 2) show sequence identity, and each coincides with a methylation-protected Dam (5 ¢ ¢ ¢ ¢ -GATC) site. Regions 1 and 2 apparently control fimB expression by an antirepression mechanism that involves additional sequences proximal to yjhA . Region 1 encompasses a 27 bp DNA sequence conserved upstream of genes known ( nanAT ) or suspected ( yjhBC ) to be involved in sialic acid metabolism, and we show that FimB expression and recombination are suppressed by Nacetylneuraminic acid. We propose that E. coli recognizes the amino sugars as a harbinger of potential host defence activation, and suppresses the expression of type 1 fimbriae in response.