title: Both alpha-haemolysin determinants contribute to full virulence of uropathogenic Escherichia coli strain 536.
abstract: Uropathogenic Escherichia coli strain 536 possesses two intact copies of the alpha-haemolysin determinant localised on distinct pathogenicity islands. The coding regions of the two hlyCABD operons are conserved; however, upstream sequences are entirely dissimilar. Consequently, expression of the encoded toxin molecules in vitro is highly different. On the other hand, the contribution of the individual determinants to the strain's virulence is the same. Isogenic mutants lacking individual hly determinants have a similar increase in LD50 value in a mouse model of urinary tract infection. Mouse lung toxicity as well as in vitro assays reveals a significant decrease in acute cytotoxicity of both mutants in comparison to the parent wild-type strain; however, the two hly mutants do not significantly differ from each other in these respects. Single channel recordings show no difference in electrophysiological characteristics of the pores formed by the individual HlyA molecules on synthetic planar lipid membranes. Nor do the paralogues have any target cell preference in an in vitro cytotoxicity assay. Our data suggest that the two hly paralogues encode identical toxin functions; however, due to different regulation of expression, they participate at distinct stages of the infectious process. Interestingly, the unrelated uropathogenic E. coli strain J96 shares the same two hly alleles, suggesting that acquisition of the two paralogues accorded a selective evolutionary advantage.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Pécs, Szigeti út 12, 7624 Pécs, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Nagy
authors.forename: Artur
authors.initials: A
authors.lastname: Altenhoefer
authors.forename: Oliver
authors.initials: O
authors.lastname: Knapp
authors.forename: Elke
authors.initials: E
authors.lastname: Maier
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dobrindt
authors.forename: Gabriele
authors.initials: G
authors.lastname: Blum-Oehler
authors.forename: Roland
authors.initials: R
authors.lastname: Benz
authors.forename: Levente
authors.initials: L
authors.lastname: Emody
authors.forename: Jörg
authors.initials: J
authors.lastname: Hacker
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D017124:Conserved Sequence; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D005798:Genes, Bacterial; D020131:Genes, Duplicate; D044404:Genomic Islands; D006460:Hemolysin Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007928:Lethal Dose 50; D008168:Lung / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D009876:Operon; D010539:Permeability; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D014552:Urinary Tract Infections / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; D037521:Virulence Factors