title: Sialic acid and N-acetylglucosamine Regulate type 1 Fimbriae Synthesis.
abstract: Type 1 fimbriae of E. coli, a chaperon-usher bacterial adhesin, are synthesized by the majority of strains of the bacterium. Although frequently produced by commensal strains, the adhesin is nevertheless a virulence factor in Extraintestinal Pathogenic E. coli (ExPEC). The role of the adhesin in pathogenesis is best understood in Uropathogenic E. coli (UPEC). Host attachment and invasion by type 1 fimbriate bacteria activates inflammatory pathways, with TLR4 signaling playing a predominant role. In a mouse model of cystitis, type 1 fimbriation not only enhances UPEC adherence to the surface of superficial umbrella cells of the bladder urothelium, but is both necessary and sufficient for their invasion. Moreover 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. The expression of type 1 fimbriation is controlled by phase variation at the transcriptional level, a mode of gene regulation in which bacteria switch reversibly between fimbriate and afimbriate phases. Phase variation has been widely considered to be a mechanism enabling immune evasion. Notwithstanding the apparently random nature of phase variation, switching of type 1 fimbrial expression is nevertheless controlled by a range of environmental signals that include the amino sugars sialic acid and N-acetylglucosamine (GlcNAc). Sialic acid plays a pivotal role in innate immunity, including signaling by the toll-like receptors. Here how sialic acid and GlcNAc control type 1 fimbriation is described and the potential significance of this regulatory response is discussed.
authors.affiliation: School of Biosciences, University of Kent, Kent, UK.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Blomfield
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics / Q000378:metabolism*; D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D003556:Cystitis / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics; D036781:Fimbriae Proteins / Q000096:biosynthesis / Q000235:genetics; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000235:genetics; D011971:Receptors, Immunologic / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D056689:Uropathogenic Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D019459:Urothelium / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; C528455:NanC protein, E coli; D018272:Porins; D011971:Receptors, Immunologic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D037521:Virulence Factors; C076610:fimbriae receptor, type 1; D036781:Fimbriae Proteins; D019158:N-Acetylneuraminic Acid; D000117:Acetylglucosamine