title: Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin.
abstract: Yersinia pestis, the agent of plague, requires the Ail (attachment invasion locus) outer membrane protein to survive in the blood and tissues of its mammalian hosts. Ail is important for both attachment to host cells and for resistance to complement-dependent bacteriolysis. Previous studies have shown that Ail interacts with components of the extracellular matrix, including fibronectin, laminin and heparan sulfate proteoglycans, and with the complement inhibitor C4b-binding protein. Here, we demonstrate that Ail-expressing Y. pestis strains bind vitronectin - a host protein with functions in cell attachment, fibrinolysis and inhibition of the complement system. The Ail-dependent recruitment of vitronectin resulted in efficient cleavage of vitronectin by the outer membrane Pla (plasminogen activator protease). Escherichia coli DH5α expressing Y. pestis Ail bound vitronectin, but not heat-treated vitronectin. The ability of Ail to directly bind vitronectin was demonstrated by ELISA using purified refolded Ail in nanodiscs.
authors.affiliation: 1​ Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
authors.forename: Sara Schesser
authors.initials: SS
authors.lastname: Bartra
authors.affiliation: 3​ Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: 3​ Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: L
authors.initials: L
authors.lastname: Miya Fujimoto
authors.affiliation: 1​ Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Ring
authors.affiliation: 2​ Division of Infectious Diseases and Immunology, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Jain
authors.affiliation: 2​ Division of Infectious Diseases and Immunology, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ram
authors.affiliation: 3​ Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Marassi
authors.affiliation: 1​ Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Plano
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D054884:Host-Pathogen Interactions; D006801:Humans; D006868:Hydrolysis; D010960:Plasminogen Activators / Q000378:metabolism; D011485:Protein Binding; D037521:Virulence Factors / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism*; D015010:Yersinia pestis / Q000378:metabolism*
chemical_list: C526543:Ail protein, Yersinia pestis; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D037521:Virulence Factors; D019096:Vitronectin; C078140:Pla protease, Yersinia pestis; D010960:Plasminogen Activators