Sialic acid and N-acetylglucosamine Regulate type 1 Fimbriae Synthesis

A model for the sialic acid Neu5Ac utilisation pathway of E. coli. Sialic acids, released from glycoconjugates in the α-anomer, cross the outer membrane by diffusion either through the sialic acid-selective channel NanC or the general porins OmpF and OmpC. The porins are presumably non-selective for the anomeric forms of Neu5Ac, so that any of the β-anomer formed spontaneously would also be taken up via this route (not shown). Periplasmic mutarotase NanM catalyses the rapid equilibrium of the α-anomer with the thermodynamically more stable β-anomer, before uptake by the inner membrane transporter NanT. Cytoplasmic Neu5Ac induces the nanATEK operon by converting NanR from the active transcriptional inhibitor (NanRA) to the inactive form (NanRI). Conversion of Neu5Ac to GlcNAc-6-P is catalysed by N-acetylneuraminate aldolase (NanA), which generates N-acetylmannosamine and pyruvate, together with N-acetylmannosamine kinase (NanK) and N-acetylmannosamine-6-phosphate-2-epimerase (NanE). To enter glycolysis, GlcNAc-6-P is converted to fructose-6-phosphate by N-acetylglucosamine-6-phosphate deacetylase (NagA), generating GlcN-6-P, followed by glucosamine-6-phosphate deaminase (NagB). The nagAB operon is induced by GlcNAc-6-P, which inactivates the transcriptional repressor NagC. GlcN-6-P can also be converted to UDP-GlcNAc, required for both peptidoglycan and LPS biosynthesis, by the sequential action of phosphoglucosamine mutase (GlmM) and the bifunctional glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase (GlmU). Proteins are shown in boxes (enzymes and porins in black-bordered boxes, while transcriptional regulators are bordered by red). The broken arrow linking GlcN-6-P to UDP-GlcNAc indicates that more than one step is involved.

The organisation of the 1.4 Kbp fimB-nanCMS intergenic region. The location of binding sites for NanR (O NR ), NagC (O NC1 and O NC2 ), IHF (ibs) and SlyA (ON SA12 ) and Dam methylation sites GATCNanR (GNanR) and GATCNagC (GNagC) are indicated. The transcription start sites for the nanCMS and fimB promoters (P), and the direction of transcription (arrows), are shown. The sections delineated by sloping parallel lines indicate where sections are omitted to allow the regulatory region shared by fimB and nanCMS (O NR to O NC2 ) to be shown to scale. The diagram is drawn to the scale indicated in base pairs (bp).