title: Sequence changes in the pilus subunit lead to tropism variation of Neisseria gonorrhoeae to human tissue.
abstract: Pili of Neisseria gonorrhoeae are correlated with increased bacterial attachment to epithelial cells and undergo both phase and antigenic variation. Phase variation of gonococcal pili can be brought about by recombination events in the pilin structural gene, pilE, or by the on/off switch in expression of PilC, a pilus biogenesis protein for which two loci exist. We have studied the binding to epithelial cell lines and to fixed tissue sections of N. gonorrhoeae MS11 derivatives and mutants carrying structurally defined PilE and PilC proteins. In situ binding studies of N. gonorrhoeae to formalin-fixed tissue sections resulted in a binding pattern similar to that obtained using viable epithelial cell lines of different origin. Piliated gonococcal clones, containing different pilE sequences, varied dramatically from one another in their efficiencies at binding to corneal and conjunctival tissue, but bound equally well to cervical and endometrial tissues. Further, the binding data suggested that PilC expression by itself, i.e. without pili, cannot confer bacterial binding and that expression of either PilC1 or PilC2 does not confer different binding properties to the bacterial cells. Possible receptors for piliated gonococci were expressed in human tissues, such as cervix, endometrium, cornea, intestine, stomach, mid-brain and meninges, but not in human kidney. Pretreatment of the target tissues with Proteinase K decreased the gonococcal binding dramatically, whereas pretreatment with neuraminidase and meta-periodate, which cleave carbon-carbon linkages between vicinal hydroxyl groups in carbohydrates, did not affect attachment of gonococci. These data argue that pilus-dependent attachment of N. gonorrhoeae to human tissue may be mediated by a eukaryotic receptor having protein characteristics, and that the pilus subunit sequence may play an important role in the interaction with human cornea.
authors.affiliation: Laboratory for Bacteriology, Karolinska Institute, Stockholm, Sweden.
authors.forename: A B
authors.initials: AB
authors.lastname: Jonsson
authors.forename: D
authors.initials: D
authors.lastname: Ilver
authors.forename: P
authors.initials: P
authors.lastname: Falk
authors.forename: J
authors.initials: J
authors.lastname: Pepose
authors.forename: S
authors.initials: S
authors.lastname: Normark
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D004848:Epithelium; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000235:genetics* / Q000472:pathogenicity; D009928:Organ Specificity; D051381:Rats; D011995:Recombination, Genetic; D013045:Species Specificity
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C079208:pilC protein, Neisseria gonorrhoeae; D036781:Fimbriae Proteins