title: Effects of Psa and F1 on the adhesive and invasive interactions of Yersinia pestis with human respiratory tract epithelial cells.
abstract: Yersinia pestis, the causative agent of plague, expresses the Psa fimbriae (pH 6 antigen) in vitro and in vivo. To evaluate the potential virulence properties of Psa for pneumonic plague, an Escherichia coli strain expressing Psa was engineered and shown to adhere to three types of human respiratory tract epithelial cells. Psa binding specificity was confirmed with Psa-coated polystyrene beads and by inhibition assays. Individual Y. pestis cells were found to be able to express the capsular antigen fraction 1 (F1) concomitantly with Psa on their surface when analyzed by flow cytometry. To better evaluate the separate effects of F1 and Psa on the adhesive and invasive properties of Y. pestis, isogenic Deltacaf (F1 genes), Deltapsa, and Deltacaf Deltapsa mutants were constructed and studied with the three respiratory tract epithelial cells. The Deltapsa mutant bound significantly less to all three epithelial cells compared to the parental wild-type strain and the Deltacaf and Deltacaf Deltapsa mutants, indicating that Psa acts as an adhesin for respiratory tract epithelial cells. An antiadhesive effect of F1 was clearly detectable only in the absence of Psa, underlining the dominance of the Psa+ phenotype. Both F1 and Psa inhibited the intracellular uptake of Y. pestis. Thus, F1 inhibits bacterial uptake by inhibiting bacterial adhesion to epithelial cells, whereas Psa seems to block bacterial uptake by interacting with a host receptor that doesn't direct internalization. The Deltacaf Deltapsa double mutant bound and invaded all three epithelial cell types well, revealing the presence of an undefined adhesin(s) and invasin(s).
authors.affiliation: Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Fengzhi
authors.initials: F
authors.lastname: Liu
authors.forename: Huaiqing
authors.initials: H
authors.lastname: Chen
authors.forename: Estela M
authors.initials: EM
authors.lastname: Galván
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Lasaro
authors.forename: Dieter M
authors.initials: DM
authors.lastname: Schifferli
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D001422:Bacterial Adhesion / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004705:Endocytosis; D004847:Epithelial Cells / Q000737:chemistry / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008863:Microspheres; D020545:Respiratory Mucosa / Q000737:chemistry / Q000382:microbiology*; D012137:Respiratory System / Q000166:cytology / Q000382:microbiology; D015010:Yersinia pestis / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C086725:caf1 protein, Yersinia pestis; C081814:pH 6 antigen, Yersinia