Integrated regulatory responses of fimB to N-acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12.
Bacterial-host attachment by means of bacterial adhesins is a key step in host colonization. Phase variation (reversible on-off switching) of the type 1 fimbrial adhesin of Escherichia coli involves a DNA inversion catalyzed by FimB (switching in either direction) or FimE (mainly on-to-off switching). fimB is separated from the divergent yjhATS operon by a large (1.4 kbp) intergenic region. Short ( approximately 28 bp) cis-active elements (regions 1 and 2) close to yjhA stimulate fimB expression and are required for sialic acid (Neu(5)Ac) sensitivity of its expression [El-Labany, S., Sohanpal, B. K., Lahooti, M., Akerman, R. & Blomfield, I. C. (2003) Mol. Microbiol. 49, 1109-1118]. 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, Neu(5)Ac inhibits the protection mediated by both NanR and NagC as expected. Type 1 fimbriae are proinflammatory, and host defenses enhance the release of both Neu(5)Ac 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.
Sohanpal
Baljinder K
BK
Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom.
El-Labany
Sammia
S
Lahooti
Maryam
M
Plumbridge
Jacqueline A
JA
Blomfield
Ian C
IC
D000117:Acetylglucosamine / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D001483:Base Sequence; D019175:DNA Methylation; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial / Q000187:drug effects; D019426:Integrases / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology*; D011995:Recombination, Genetic / Q000187:drug effects; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C477082:NanR protein, E coli; C084955:PdhR protein, E coli; D012097:Repressor Proteins; D014157:Transcription Factors; C081956:fimB protein, E coli; C067862:nagC protein, E coli; D019426:Integrases; D019158:N-Acetylneuraminic Acid; D000117:Acetylglucosamine