title: Contribution of trimeric autotransporter C-terminal domains of oligomeric coiled-coil adhesin (Oca) family members YadA, UspA1, EibA, and Hia to translocation of the YadA passenger domain and virulence of Yersinia enterocolitica.
abstract: The Oca family is a novel class of autotransporter-adhesins with highest structural similarity in their C-terminal transmembrane region, which supposedly builds a beta-barrel pore in the outer membrane (OM). The prototype of the Oca family is YadA, an adhesin of Yersinia enterocolitica and Yersinia pseudotuberculosis. YadA forms a homotrimeric lollipop-like structure on the bacterial surface. The C-terminal regions of three YadA monomers form a barrel in the OM and translocate the trimeric N-terminal passenger domain, consisting of stalk, neck, and head region to the exterior. To elucidate the structural and functional role of the C-terminal translocator domain (TLD) and to assess its promiscuous capability with respect to transport of related passenger domains, we constructed chimeric YadA proteins, which consist of the N-terminal YadA passenger domain and C-terminal TLDs of Oca family members UspA1 (Moraxella catarrhalis), EibA (Escherichia coli), and Hia (Haemophilus influenzae). These constructs were expressed in Y. enterocolitica and compared for OM localization, surface exposure, oligomerization, adhesion properties, serum resistance, and mouse virulence. We demonstrate that all chimeric YadA proteins translocated the YadA passenger domain across the OM. Y. enterocolitica strains producing YadA chimeras or wild-type YadA showed comparable binding to collagen and epithelial cells. However, strains producing YadA chimeras were attenuated in serum resistance and mouse virulence. These results demonstrate for the first time that TLDs of Oca proteins of different origin are efficient translocators of the YadA passenger domain and that the cognate TLD of YadA is essential for bacterial survival in human serum and mouse virulence.
authors.affiliation: Max von Pettenkofer Institute for Hygiene and Medical Microbiology, Ludwig Maximilians University Munich, Pettenkoferstrasse 9a, 80336 Munich, Germany. heesemann@mvp.uni-muenchen.de.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Ackermann
authors.forename: Maximilian
authors.initials: M
authors.lastname: Tiller
authors.forename: Gisela
authors.initials: G
authors.lastname: Anding
authors.forename: Andreas
authors.initials: A
authors.lastname: Roggenkamp
authors.forename: Jürgen
authors.initials: J
authors.lastname: Heesemann
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006193:Haemophilus influenzae / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D008958:Models, Molecular; D001936:Moraxella catarrhalis / Q000235:genetics; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D044967:Serum / Q000276:immunology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D015009:Yersinia Infections; D015008:Yersinia enterocolitica / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C440641:EibA protein, E coli; D029968:Escherichia coli Proteins; C429644:Hia adhesin; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C089675:UspA protein, Moraxella catarrhalis; D037521:Virulence Factors; C064832:YadA protein, Yersinia; D003094:Collagen