title: Moraxella catarrhalis binding to host cellular receptors is mediated by sequence-specific determinants not conserved among all UspA1 protein variants.
abstract: The Moraxella catarrhalis ubiquitous surface proteins (UspAs) are autotransporter molecules reported to interact with a variety of different host proteins and to affect processes ranging from serum resistance to cellular adhesion. The role of UspA1 as an adhesin has been confirmed with a number of different human cell types and is mediated by binding to eukaryotic proteins including carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs), fibronectin, and laminin. A distinct difference in the ability of prototypical M. catarrhalis strains to adhere to CEACAM-expressing cell lines prompted us to perform strain-specific structure-function analyses of UspA1 proteins. In this study, we characterized CEACAM binding by a diverse set of UspA1 proteins and showed that 3 out of 10 UspA1 proteins were incapable of binding CEACAM. This difference resulted from the absence of a distinct CEACAM binding motif in nonadhering strains. Our sequence analysis also revealed a single M. catarrhalis isolate that lacked the fibronectin-binding motif and was defective in adherence to Chang conjunctival epithelial cells. These results clearly demonstrate that UspA1-associated adhesive functions are not universally conserved. Instead, UspA1 proteins must be considered as variants with the potential to confer both different cell tropisms and host cell responses.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brooks
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sedillo
authors.forename: Nikki
authors.initials: N
authors.lastname: Wagner
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Attia
authors.forename: Henry
authors.initials: H
authors.lastname: Wong
authors.forename: Cassie A
authors.initials: CA
authors.lastname: Laurence
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Hansen
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gray-Owen
mesh_terms: D000595:Amino Acid Sequence; D001422:Bacterial Adhesion / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D017386:Sequence Homology, Amino Acid
chemical_list: D001425:Bacterial Outer Membrane Proteins; D015815:Cell Adhesion Molecules; C089675:UspA protein, Moraxella catarrhalis