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Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin
- Authors: Sara Schesser Bartra1 , Yi Ding3 , L. Miya Fujimoto3 , Joshua G. Ring1 , Vishal Jain2 , Sanjay Ram2 , Francesca M. Marassi3 , Gregory V. Plano1
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1 1 Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA 2 2 Division of Infectious Diseases and Immunology, University of Massachusetts Medical Center, Worcester, MA 01605, USA 3 3 Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA
- Correspondence Gregory V. Plano [email protected]
- First Published Online: 01 November 2015, Microbiology 161: 2174-2183, doi: 10.1099/mic.0.000179
- Subject: Host-Microbe Interaction
- Received:
- Accepted:
- Revised:
- Cover date:




Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin, Page 1 of 1
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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.
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Edited by: P. Oyston
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Abbreviations: C4BP C4b-binding protein ECM extracellular matrix HBS heparin-binding site HIS heat-inactivated sera MAC membrane attack complex NHS normal human sera PAI plasminogen activator inhibitor T3SS type III secretion system
© 2015 The Authors
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Attia A.S. , Ram S. , Rice P.A. , Hansen E.J. . ( 2006;). Binding of vitronectin by the Moraxella catarrhalis UspA2 protein interferes with late stages of the complement cascade. Infect Immun 74: 1597––1611 [CrossRef] [PubMed].
-
Bartra S.S. , Jackson M.W. , Ross J.A. , Plano G.V. . ( 2006;). Calcium-regulated type III secretion of Yop proteins by an Escherichia coli hha mutant carrying a Yersinia pestis pCD1 virulence plasmid. Infect Immun 74: 1381––1386 [CrossRef] [PubMed].
-
Bartra S.S. , Styer K.L. , O'Bryant D.M. , Nilles M.L. , Hinnebusch B.J. , Aballay A. , Plano G.V. . ( 2008;). Resistance of Yersinia pestis to complement-dependent killing is mediated by the Ail outer membrane protein. Infect Immun 76: 612––622 [CrossRef] [PubMed].
-
Bernhard S. , Fleury C. , Su Y.C. , Zipfel P.F. , Koske I. , Nordström T. , Riesbeck K. . ( 2014;). Outer membrane protein OlpA contributes to Moraxella catarrhalis serum resistance via interaction with factor H and the alternative pathway. J Infect Dis 210: 1306––1310 [CrossRef] [PubMed].
-
Blom A.M. , Hallström T. , Riesbeck K. . ( 2009;). Complement evasion strategies of pathogens-acquisition of inhibitors and beyond. Mol Immunol 46: 2808––2817 [CrossRef] [PubMed].
-
Cambau E. , Bordon F. , Collatz E. , Gutmann L. . ( 1993;). Novel gyrA point mutation in a strain of Escherichia coli resistant to fluoroquinolones but not to nalidixic acid. Antimicrob Agents Chemother 37: 1247––1252 [CrossRef] [PubMed].
-
Chain D. , Korc-Grodzicki B. , Kreizman T. , Shaltiel S. . ( 1991;). Endogenous cleavage of the Arg-379-Ala-380 bond in vitronectin results in a distinct conformational change which ‘buries’ Ser-378, its site of phosphorylation by protein kinase A. Biochem J 274: 387––394 [CrossRef] [PubMed].
-
Ding Y. , Fujimoto L.M. , Yao Y. , Plano G.V. , Marassi F.M. . ( 2015;). Influence of the lipid membrane environment on structure and activity of the outer membrane protein Ail from Yersinia pestis . Biochim Biophys Acta 1848: 712––720 [CrossRef] [PubMed].
-
Duensing T.D. , van Putten J.P. . ( 1997;). Vitronectin mediates internalization of Neisseria gonorrhoeae by Chinese hamster ovary cells. Infect Immun 65: 964––970 [PubMed].
-
Duensing T.D. , Wing J.S. , van Putten J.P. . ( 1999;). Sulfated polysaccharide-directed recruitment of mammalian host proteins: a novel strategy in microbial pathogenesis. Infect Immun 67: 4463––4468 [PubMed].
-
Felek S. , Krukonis E.S. . ( 2009;). The Yersinia pestis Ail protein mediates binding and Yop delivery to host cells required for plague virulence. Infect Immun 77: 825––836 [CrossRef] [PubMed].
-
Felek S. , Tsang T.M. , Krukonis E.S. . ( 2010;). Three Yersinia pestis adhesins facilitate Yop delivery to eukaryotic cells and contribute to plague virulence. Infect Immun 78: 4134––4150 [CrossRef] [PubMed].
-
Ferracci F. , Day J.B. , Ezelle H.J. , Plano G.V. . ( 2004;). Expression of a functional secreted YopN-TyeA hybrid protein in Yersinia pestis is the result of a+1 translational frameshift event. J Bacteriol 186: 5160––5166 [CrossRef] [PubMed].
-
Forsberg A. , Rosqvist R. , Wolf-Watt H. . ( 1994;). Regulation and polarized transfer of the Yersinia outer proteins (Yops) involved in antiphagocytosis. Trends Microbiol 2: 14––19 [CrossRef] [PubMed].
-
Griffiths N.J. , Hill D.J. , Borodina E. , Sessions R.B. , Devos N.I. , Feron C.M. , Poolman J.T. , Virji M. . ( 2011;). Meningococcal surface fibril (Msf) binds to activated vitronectin and inhibits the terminal complement pathway to increase serum resistance. Mol Microbiol 82: 1129––1149 [CrossRef] [PubMed].
-
Grosdent N. , Maridonneau-Parini I. , Sory M.P. , Cornelis G.R. . ( 2002;). Role of Yops and adhesins in resistance of Yersinia enterocolitica to phagocytosis. Infect Immun 70: 4165––4176 [CrossRef] [PubMed].
-
Haiko J. , Laakkonen L. , Juuti K. , Kalkkinen N. , Korhonen T.K. . ( 2010;). The omptins of Yersinia pestis and Salmonella enterica cleave the reactive center loop of plasminogen activator inhibitor 1. J Bacteriol 192: 4553––4561 [CrossRef] [PubMed].
-
Hallström T. , Trajkovska E. , Forsgren A. , Riesbeck K. . ( 2006;). Haemophilus influenzae surface fibrils contribute to serum resistance by interacting with vitronectin. J Immunol 177: 430––436 [CrossRef] [PubMed].
-
Hallström T. , Jarva H. , Riesbeck K. , Blom A.M. . ( 2007;). Interaction with C4b-binding protein contributes to nontypeable Haemophilus influenzae serum resistance. J Immunol 178: 6359––6366 [CrossRef] [PubMed].
-
Hallström T. , Blom A.M. , Zipfel P.F. , Riesbeck K. . ( 2009;). Nontypeable Haemophilus influenzae protein E binds vitronectin and is important for serum resistance. J Immunol 183: 2593––2601 [CrossRef] [PubMed].
-
Hallström T. , Singh B. , Resman F. , Blom A.M. , Mörgelin M. , Riesbeck K. . ( 2011;). Haemophilus influenzae protein E binds to the extracellular matrix by concurrently interacting with laminin and vitronectin. J Infect Dis 204: 1065––1074 [CrossRef] [PubMed].
-
Härdig Y. , Hillarp A. , Dahlbäck B. . ( 1997;). The amino-terminal module of the C4b-binding protein alpha-chain is crucial for C4b binding and factor I-cofactor function. Biochem J 323: 469––475 [CrossRef] [PubMed].
-
Hinnebusch B.J. , Jarrett C.O. , Callison J.A. , Gardner D. , Buchanan S.K. , Plano G.V. . ( 2011;). Role of the Yersinia pestis Ail protein in preventing a protective polymorphonuclear leukocyte response during bubonic plague. Infect Immun 79: 4984––4989 [CrossRef] [PubMed].
-
Ho D.K. , Skurnik M. , Blom A.M. , Meri S. . ( 2014;). Yersinia pestis Ail recruitment of C4b-binding protein leads to factor I-mediated inactivation of covalently and noncovalently bound C4b. Eur J Immunol 44: 742––751 [CrossRef].
-
Kolodziejek A.M. , Sinclair D.J. , Seo K.S. , Schnider D.R. , Deobald C.F. , Rohde H.N. , Viall A.K. , Minnich S.S. , Hovde C.J. , other authors . ( 2007;). Phenotypic characterization of OmpX, an Ail homologue of Yersinia pestis KIM. Microbiology 153: 2941––2951 [CrossRef] [PubMed].
-
Kolodziejek A.M. , Schnider D.R. , Rohde H.N. , Wojtowicz A.J. , Bohach G.A. , Minnich S.A. , Hovde C.J. . ( 2010;). Outer membrane protein X (Ail) contributes to Yersinia pestis virulence in pneumonic plague and its activity is dependent on the lipopolysaccharide core length. Infect Immun 78: 5233––5243 [CrossRef] [PubMed].
-
Lewis L.A. , Ram S. . ( 2014;). Meningococcal disease and the complement system. Virulence 5: 98––126 [CrossRef] [PubMed].
-
Lindler L.E. , Tall B.D. . ( 1993;). Yersinia pestis pH 6 antigen forms fimbriae and is induced by intracellular association with macrophages. Mol Microbiol 8: 311––324 [CrossRef] [PubMed].
-
Lorange E.A. , Race B.L. , Sebbane F. , Hinnebusch B.J. . ( 2005;). Poor vector competence of fleas and the evolution of hypervirulence in Yersinia pestis . J Infect Dis 191: 1907––1912 [CrossRef] [PubMed].
-
Lössner D. , Abou-Ajram C. , Benge A. , Aumercier M. , Schmitt M. , Reuning U. . ( 2009;). Integrin alphavbeta3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription. J Cell Physiol 220: 367––375 [CrossRef] [PubMed].
-
Marassi F.M. , Ding Y. , Schwieters C.D. , Tian Y. , Yao Y. . ( 2015;). Backbone structure of Yersinia pestis Ail determined in micelles by NMR-restrained simulated annealing with implicit membrane solvation. J Biomol NMR 63: 59––65 [CrossRef] [PubMed].
-
Milis L. , Morris C.A. , Sheehan M.C. , Charlesworth J.A. , Pussell B.A. . ( 1993;). Vitronectin-mediated inhibition of complement: evidence for different binding sites for C5b-7 and C9. Clin Exp Immunol 92: 114––119 [CrossRef] [PubMed].
-
Miller V.L. , Bliska J.B. , Falkow S. . ( 1990;). Nucleotide sequence of the Yersinia enterocolitica ail gene and characterization of the Ail protein product. J Bacteriol 172: 1062––1069 [PubMed].
-
Miller V.L. , Beer K.B. , Heusipp G. , Young B.M. , Wachtel M.R. . ( 2001;). Identification of regions of Ail required for the invasion and serum resistance phenotypes. Mol Microbiol 41: 1053––1062 [CrossRef] [PubMed].
-
Nath A. , Atkins W.M. , Sligar S.G. . ( 2007;). Applications of phospholipid bilayer nanodiscs in the study of membranes and membrane proteins. Biochemistry 46: 2059––2069 [CrossRef] [PubMed].
-
Ngampasutadol J. , Ram S. , Blom A.M. , Jarva H. , Jerse A.E. , Lien E. , Goguen J. , Gulati S. , Rice P.A. . ( 2005;). Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection. Proc Natl Acad Sci U S A 102: 17142––17147 [CrossRef] [PubMed].
-
Nordström T. , Blom A.M. , Forsgren A. , Riesbeck K. . ( 2004;). The emerging pathogen Moraxella catarrhalis interacts with complement inhibitor C4b binding protein through ubiquitous surface proteins A1 and A2. J Immunol 173: 4598––4606 [CrossRef] [PubMed].
-
Perry R.D. , Fetherston J.D. . ( 1997;). Yersinia pestis – etiologic agent of plague. Clin Microbiol Rev 10: 35––66 [PubMed].
-
Putzker M. , Sauer H. , Sobe D. . ( 2001;). Plague and other human infections caused by Yersinia species. Clin Lab 47: 453––466 [PubMed].
-
Ram S. , Mackinnon F.G. , Gulati S. , McQuillen D.P. , Vogel U. , Frosch M. , Elkins C. , Guttormsen H.K. , Wetzler L.M. , other authors . ( 1999;). The contrasting mechanisms of serum resistance of Neisseria gonorrhoeae and group B Neisseria meningitidis . Mol Immunol 36: 915––928 [CrossRef] [PubMed].
-
Ram S. , Cullinane M. , Blom A.M. , Gulati S. , McQuillen D.P. , Monks B.G. , O'Connell C. , Boden R. , Elkins C. , other authors . ( 2001;). Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae . J Exp Med 193: 281––295 [CrossRef] [PubMed].
-
Ritchie T.K. , Grinkova Y.V. , Bayburt T.H. , Denisov I.G. , Zolnerciks J.K. , Atkins W.M. , Sligar S.G. . ( 2009;). Reconstitution of membrane proteins in phospholipid bilayer nanodiscs. Methods Enzymol 464: 211––231 [CrossRef] [PubMed].
-
Rosqvist R. , Skurnik M. , Wolf-Watz H. . ( 1988;). Increased virulence of Yersinia pseudotuberculosis by two independent mutations. Nature 334: 522––524 [CrossRef] [PubMed].
-
Sa E Cunha C. , Griffiths N.J. , Virji M. . ( 2010;). Neisseria meningitidis Opc invasin binds to the sulphated tyrosines of activated vitronectin to attach to and invade human brain endothelial cells. PLoS Pathog 6: e1000911 [CrossRef] [PubMed].
-
Salonen E.M. , Vaheri A. , Pöllänen J. , Stephens R. , Andreasen P. , Mayer M. , Danø K. , Gailit J. , Ruoslahti E. . ( 1989;). Interaction of plasminogen activator inhibitor (PAI-1) with vitronectin. J Biol Chem 264: 6339––6343 [PubMed].
-
Sane D.C. , Moser T.L. , Parker C.J. , Seiffert D. , Loskutoff D.J. , Greenberg C.S. . ( 1990;). Highly sulfated glycosaminoglycans augment the cross-linking of vitronectin by guinea pig liver transglutaminase. Functional studies of the cross-linked vitronectin multimers. J Biol Chem 265: 3543––3548 [PubMed].
-
Sebbane F. , Jarrett C.O. , Gardner D. , Long D. , Hinnebusch B.J. . ( 2006;). Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. Proc Natl Acad Sci U S A 103: 5526––5530 [CrossRef] [PubMed].
-
Simonet M. , Riot B. , Fortineau N. , Berche P. . ( 1996;). Invasin production by Yersinia pestis is abolished by insertion of an IS200-like element within the inv gene. Infect Immun 64: 375––379 [PubMed].
-
Singh B. , Su Y.C. , Riesbeck K. . ( 2010;). Vitronectin in bacterial pathogenesis: a host protein used in complement escape and cellular invasion. Mol Microbiol 78: 545––560 [CrossRef] [PubMed].
-
Skurnik M. , Wolf-Watz H. . ( 1989;). Analysis of the yopA gene encoding the Yop1 virulence determinants of Yersinia spp. Mol Microbiol 3: 517––529 [CrossRef] [PubMed].
-
Sodeinde O.A. , Subrahmanyam Y.V. , Stark K. , Quan T. , Bao Y. , Goguen J.D. . ( 1992;). A surface protease and the invasive character of plague. Science 258: 1004––1007 [CrossRef] [PubMed].
-
Tsang T.M. , Felek S. , Krukonis E.S. . ( 2010;). Ail binding to fibronectin facilitates Yersinia pestis binding to host cells and Yop delivery. Infect Immun 78: 3358––3368 [CrossRef] [PubMed].
-
Une T. , Brubaker R.R. . ( 1984;). In vivo comparison of avirulent Vwa- and Pgm- or Pstr phenotypes of yersiniae. Infect Immun 43: 895––900 [PubMed].
-
Vandeputte-Rutten L. , Kramer R.A. , Kroon J. , Dekker N. , Egmond M.R. , Gros P. . ( 2001;). Crystal structure of the outer membrane protease OmpT from Escherichia coli suggests a novel catalytic site. EMBO J 20: 5033––5039 [CrossRef] [PubMed].
-
Viboud G.I. , Bliska J.B. . ( 2004;). Yersinia outer proteins: role in modulation of host cell signalling responses and pathogenesis. Annu Rev Microbiol 59: 69––89 [PubMed].[CrossRef]
-
Vogt J. , Schulz G.E. . ( 1999;). The structure of the outer membrane protein OmpX from Escherichia coli reveals possible mechanisms of virulence. Structure 7: 1301––1309 [CrossRef] [PubMed].
-
Wachtel M.R. , Miller V.L. . ( 1995;). In vitro and in vivo characterization of an ail mutant of Yersinia enterocolitica . Infect Immun 63: 2541––2548 [PubMed].
-
Wiman B. . ( 1996;). Plasminogen activator inhibitor 1 in thrombotic disease. Curr Opin Hematol 3: 372––378 [CrossRef] [PubMed].
-
Wiman B. , Almquist A. , Sigurdardottir O. , Lindahl T. . ( 1988;). Plasminogen activator inhibitor 1 (PAI) is bound to vitronectin in plasma. FEBS Lett 242: 125––128 [CrossRef] [PubMed].
-
Yamashita S. , Lukacik P. , Barnard T.J. , Noinaj N. , Felek S. , Tsang T.M. , Krukonis E.S. , Hinnebusch B.J. , Buchanan S.K. . ( 2011;). Structural insights into Ail-mediated adhesion in Yersinia pestis . Structure 19: 1672––1682 [CrossRef] [PubMed].

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