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Impact of sequence diversity in the Moraxella catarrhalis UspA2/UspA2H head domain on vitronectin binding and antigenic variation
KTH, Centres, Science for Life Laboratory, SciLifeLab.
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2013 (English)In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 15, no 5, 375-387 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2013. Vol. 15, no 5, 375-387 p.
Keyword [en]
Moraxella catarrhalis, Sequence heterogeneity, UspA2, UspA2H, Vitronectin
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
URN: urn:nbn:se:kth:diva-124468DOI: 10.1016/j.micinf.2013.02.004ISI: 000319539000005ScopusID: 2-s2.0-84876881711OAI: diva2:636147
Swedish Society for Medical Research (SSMF)

QC 20130709

Available from: 2013-07-09 Created: 2013-07-05 Last updated: 2013-07-09Bibliographically approved

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Hallström, Björn M.
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Science for Life Laboratory, SciLifeLab
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Microbes and infection
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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