title: Impact of sequence diversity in the Moraxella catarrhalis UspA2/UspA2H head domain on vitronectin binding and antigenic variation.
abstract: The nasopharyngeal pathogen Moraxella catarrhalis recruits vitronectin to subvert complement-mediated killing. Ubiquitous surface protein (UspA) 2 and its hybrid form UspA2H bind vitronectin at the highly diverse N-terminal head domain. Here we characterized the sequence diversity of the head domain in multiple M. catarrhalis clinical isolates (n = 51) with focus on binding of vitronectin. The head domain of the uspA2 genes from 40 isolates were clustered according to an N-terminal sequence motif of UspA2 (NTER2), i.e., NTER2A (55% of uspA2 variants), NTER2B (32.5%), NTER2C (5%), and finally a group without an NTER2 (7.5%). Isolates harbouring the uspA2H gene (n = 11) contained N-terminal GGG repeats. Vitronectin binding to isolates having UspA2 did not correlate to variation in the NTER2 motifs but occurred in UspA2H containing 6 or ≥11 of GGG repeats. Analyses of recombinant UspA2/UspA2H head domains of multiple variants showed UspA2-dependent binding to the C-terminal of vitronectin. Furthermore, polyclonal anti-UspA2 antibodies revealed that the head domain of the majority of Moraxella UspA2/2H was antigenically unrelated, whereas the full length molecules were recognized. In conclusion, the head domains of UspA2/2H have extensive sequence polymorphism without losing vitronectin-binding capacity promoting a general evasion of the host immune system.
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine Malmö, Lund University, Jan Waldenströms gata 59, SE-205 02 Malmö, Sweden.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Su
authors.forename: Björn M
authors.initials: BM
authors.lastname: Hallström
authors.forename: Sara
authors.initials: S
authors.lastname: Bernhard
authors.forename: Birendra
authors.initials: B
authors.lastname: Singh
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
mesh_terms: D000940:Antigenic Variation; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000235:genetics* / Q000276:immunology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017422:Sequence Analysis, DNA; D019096:Vitronectin / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004269:DNA, Bacterial; C089675:UspA protein, Moraxella catarrhalis; D019096:Vitronectin