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The emerging pathogen Moraxella catarrhalis interacts with complement inhibitor C4b binding protein through ubiquitous surface proteins A1 and A2

Nordström, Therése LU ; Blom, Anna LU ; Forsgren, Arne LU and Riesbeck, Kristian LU (2004) In Journal of Immunology 173(7). p.4598-4606
Abstract
Moraxella catarrhalis ubiquitous surface protein A2 (UspA2) mediates resistance to the bactericidal activity of normal human serum. In this study, an interaction between the complement fluid phase regulator of the classical pathway, C4b binding protein (C4BP), and M. catarrhalis mutants lacking UspA1 and/or UspA2 was analyzed by flow cytometry and a RIA. Two clinical isolates of M. catarrhalis expressed UspA2 at a higher density than UspA1. The UspA1 mutants showed a decreased C4BP binding (37.6% reduction), whereas the UspA2-deficient Moraxella mutants displayed a strongly reduced (94.6%) C4BP? binding compared with the wild type. In addition, experiments with recombinantly expressed UspA1(50-770) and UspA2(30-539) showed that C4BP... (More)
Moraxella catarrhalis ubiquitous surface protein A2 (UspA2) mediates resistance to the bactericidal activity of normal human serum. In this study, an interaction between the complement fluid phase regulator of the classical pathway, C4b binding protein (C4BP), and M. catarrhalis mutants lacking UspA1 and/or UspA2 was analyzed by flow cytometry and a RIA. Two clinical isolates of M. catarrhalis expressed UspA2 at a higher density than UspA1. The UspA1 mutants showed a decreased C4BP binding (37.6% reduction), whereas the UspA2-deficient Moraxella mutants displayed a strongly reduced (94.6%) C4BP? binding compared with the wild type. In addition, experiments with recombinantly expressed UspA1(50-770) and UspA2(30-539) showed that C4BP (range, 1-1000 nM) bound to the two proteins in a dose-dependent manner. The equilibrium constants (K-D) for the USpA1(50-770) and USpA(30-539) interactions with a single subunit of C4BP were 13 muM and 1.1 muM, respectively. The main isoform of COP contains seven identical alpha-chains and one beta-chain linked together with disulfide bridges, and the a-chains contain eight complement control protein (CCP) modules. The UspA1 and A2 bound to the a-chain of C4BP, and experiments with C4BP lacking CCP2, CCP5, or CCP7 showed that these three CCPs were important for the Usp binding. Importantly, C4BP bound to the surface of M. catarrhalis retained its cofactor activity as determined by analysis of C4b degradation. Taken together, M. catarrhalis interferes with the classical complement activation pathway by binding C4BP to UspA1 and UspA2. (Less)
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Contribution to journal
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published
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Journal of Immunology
volume
173
issue
7
pages
4598 - 4606
publisher
American Association of Immunologists
external identifiers
  • pmid:15383594
  • wos:000224072600043
  • scopus:4644303454
ISSN
1550-6606
language
English
LU publication?
yes
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3afda9f7-0ffd-4289-98ef-06a08bc8fbfa (old id 266346)
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http://www.jimmunol.org/cgi/content/abstract/173/7/4598
date added to LUP
2007-10-29 09:50:31
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2017-11-05 04:22:19
@article{3afda9f7-0ffd-4289-98ef-06a08bc8fbfa,
  abstract     = {Moraxella catarrhalis ubiquitous surface protein A2 (UspA2) mediates resistance to the bactericidal activity of normal human serum. In this study, an interaction between the complement fluid phase regulator of the classical pathway, C4b binding protein (C4BP), and M. catarrhalis mutants lacking UspA1 and/or UspA2 was analyzed by flow cytometry and a RIA. Two clinical isolates of M. catarrhalis expressed UspA2 at a higher density than UspA1. The UspA1 mutants showed a decreased C4BP binding (37.6% reduction), whereas the UspA2-deficient Moraxella mutants displayed a strongly reduced (94.6%) C4BP? binding compared with the wild type. In addition, experiments with recombinantly expressed UspA1(50-770) and UspA2(30-539) showed that C4BP (range, 1-1000 nM) bound to the two proteins in a dose-dependent manner. The equilibrium constants (K-D) for the USpA1(50-770) and USpA(30-539) interactions with a single subunit of C4BP were 13 muM and 1.1 muM, respectively. The main isoform of COP contains seven identical alpha-chains and one beta-chain linked together with disulfide bridges, and the a-chains contain eight complement control protein (CCP) modules. The UspA1 and A2 bound to the a-chain of C4BP, and experiments with C4BP lacking CCP2, CCP5, or CCP7 showed that these three CCPs were important for the Usp binding. Importantly, C4BP bound to the surface of M. catarrhalis retained its cofactor activity as determined by analysis of C4b degradation. Taken together, M. catarrhalis interferes with the classical complement activation pathway by binding C4BP to UspA1 and UspA2.},
  author       = {Nordström, Therése and Blom, Anna and Forsgren, Arne and Riesbeck, Kristian},
  issn         = {1550-6606},
  language     = {eng},
  number       = {7},
  pages        = {4598--4606},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {The emerging pathogen Moraxella catarrhalis interacts with complement inhibitor C4b binding protein through ubiquitous surface proteins A1 and A2},
  volume       = {173},
  year         = {2004},
}