Chapter 5 : Sialic acid and N-acetylglucosamine Regulate type 1 Fimbriae Synthesis

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Sialic acid and N-acetylglucosamine Regulate type 1 Fimbriae Synthesis, Page 1 of 2

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Type 1 fimbriae of , a member of the chaperon-usher family of bacterial adhesins, are synthesised by the majority of strains of the bacterium. Although frequently produced by commensal strains, the adhesin is nevertheless a virulence factor in extraintestinal pathogenic (ExPEC). The role of the adhesin in pathogenesis is best understood in uropathogenic (UPEC). Host attachment and particularly invasion by type 1 fimbriate bacteria activates inflammatory pathways, with TLR4 signalling playing a predominant role ( ). In a mouse model of cystitis, type 1 fimbriation not only enhances UPEC adherence to oligomannosides of uroplakin 1a on the surface of superficial umbrella cells of the bladder urothelium, but is both necessary and sufficient for their invasion ( ). Moreover, more surprisingly, the adhesin plays a role in the formation of transient intracellular bacterial communities (IBCs) within the cytoplasm of urothelial cells as part of UPEC cycles of invasion ( ).

Citation: Blomfield I. 2015. Sialic acid and N-acetylglucosamine Regulate type 1 Fimbriae Synthesis, p 95-103. In Conway T, Cohen P (ed), Metabolism and Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MBP-0015-2014
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Figure 1

A model for the sialic acid Neu5Ac utilisation pathway of . 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 operon by converting NanR from the active transcriptional inhibitor (NanR) to the inactive form (NanR). 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 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.

Citation: Blomfield I. 2015. Sialic acid and N-acetylglucosamine Regulate type 1 Fimbriae Synthesis, p 95-103. In Conway T, Cohen P (ed), Metabolism and Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MBP-0015-2014
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Image of Figure 2
Figure 2

The organisation of the 1.4 Kbp intergenic region. The location of binding sites for NanR ( ), NagC ( and ), IHF () and SlyA ( ) and Dam methylation sites GATC (G) and GATC (G) are indicated. The transcription start sites for the and 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 and ( to ) to be shown to scale. The diagram is drawn to the scale indicated in base pairs (bp).

Citation: Blomfield I. 2015. Sialic acid and N-acetylglucosamine Regulate type 1 Fimbriae Synthesis, p 95-103. In Conway T, Cohen P (ed), Metabolism and Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MBP-0015-2014
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