Impact of sequence diversity in the Moraxella catarrhalis UspA2/UspA2H head domain on vitronectin binding and antigenic variation

详细信息    查看全文

• 作者：Yu-Ching Su^a ; Bjö ; rn M. Hallströ ; m^b ; Sara Bernhard^a ; Birendra Singh^a ; Kristian Riesbeck^a ; ^{kristian.riesbeck@med.lu.se}
• 关键词：Moraxella catarrhalis ; Sequence heterogeneity ; UspA2 ; UspA2H ; Vitronectin
• 刊名：Microbes and Infection
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：15
• 期：5
• 页码：375-387
• 全文大小：1726 K

文摘

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 ¡Ý11 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.