title: Ail binding to fibronectin facilitates Yersinia pestis binding to host cells and Yop delivery.
abstract: Yersinia pestis, the causative agent of plague, evades host immune responses and rapidly causes disease. The Y. pestis adhesin Ail mediates host cell binding and is critical for Yop delivery. To identify the Ail receptor(s), Ail was purified following overexpression in Escherichia coli. Ail bound specifically to fibronectin, an extracellular matrix protein with the potential to act as a bridge between Ail and host cells. Ail expressed by E. coli also mediated binding to purified fibronectin, and Ail-mediated E. coli adhesion to host cells was dependent on fibronectin. Ail expressed by Y. pestis bound purified fibronectin, as did the Y. pestis adhesin plasminogen activator (Pla). However, a KIM5 Delta ail mutant had decreased binding to host cells, while a KIM5 Delta pla mutant had no significant defect in adhesion. Furthermore, treatment with antifibronectin antibodies decreased Ail-mediated adhesion by KIM5 and the KIM5 Delta pla mutant, indicating that the Ail-fibronectin interaction was important for cell binding. Finally, antifibronectin antibodies inhibited the KIM5-mediated cytotoxicity of host cells in an Ail-dependent fashion. These data indicate that Ail is a key adhesin that mediates binding to host cells through interaction with fibronectin on the surface of host cells, and this interaction is important for Yop delivery by Y. pestis.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan School of Medicine, 1011 N. University, Ann Arbor, MI 48109-1078, USA.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Tsang
authors.forename: Suleyman
authors.initials: S
authors.lastname: Felek
authors.forename: Eric S
authors.initials: ES
authors.lastname: Krukonis
mesh_terms: D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D037521:Virulence Factors / Q000378:metabolism*; D015010:Yersinia pestis / Q000472:pathogenicity*
chemical_list: C526543:Ail protein, Yersinia pestis; D001425:Bacterial Outer Membrane Proteins; D005353:Fibronectins; D011994:Recombinant Proteins; D037521:Virulence Factors