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Moraxella catarrhalis binds plasminogen to evade host innate immunity.

Singh, Birendra LU ; Tamim, Al-Jubair LU ; Voraganti, Chandrashekhar; Andersson, Tobias; Mukherjee, Oindrilla LU ; Su, Yu-Ching; Zipfel, Peter and Riesbeck, Kristian LU (2015) In Infection and Immunity 83(9). p.3458-3469
Abstract
Several bacterial species recruit the complement regulators C4b binding protein, Factor H and vitronectin resulting in resistance against the bactericidal activity of human serum. It has recently been demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades C3b and C5. In this study, we found that a series of clinical isolates (n=58) of the respiratory pathogen M. catarrhalis, which is commonly isolated from pre-school children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein (Usp) A2 and A2 hybrid (UspA2H) was identified as the plasminogen-binding factor in the outer membrane proteome of Moraxella. Furthermore, expression of... (More)
Several bacterial species recruit the complement regulators C4b binding protein, Factor H and vitronectin resulting in resistance against the bactericidal activity of human serum. It has recently been demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades C3b and C5. In this study, we found that a series of clinical isolates (n=58) of the respiratory pathogen M. catarrhalis, which is commonly isolated from pre-school children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein (Usp) A2 and A2 hybrid (UspA2H) was identified as the plasminogen-binding factor in the outer membrane proteome of Moraxella. Furthermore, expression of a series of truncated recombinant UspA2 and UspA2H followed by a detailed analysis of protein-protein interactions suggested that the N-terminal head domains bound to the kringle domains of plasminogen. The binding affinity constant (KD) for UspA2(30-539) and UspA2H(50-720) to immobilized plasminogen was 4.8x10(-8) M and 3.13x10(-8) M, respectively, as measured by Biolayer inferometry. Plasminogen bound to intact M. catarrhalis or to recombinant UspA2/A2H was readily accessible for urokinase plasminogen activator that converted the zymogen into active plasmin as verified by the specific substrate S-2251, and a degradation assay comprising fibrinogen. Importantly, plasmin bound at the bacterial surface also degraded C3b and C5 that consequently may contribute to a reduced bacterial killing. Our findings suggest that binding of plasminogen to M. catarrhalis may lead to increased virulence and hence more efficient colonization of the host. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
83
issue
9
pages
3458 - 3469
publisher
American Society for Microbiology
external identifiers
  • pmid:26099590
  • wos:000359435600011
  • scopus:84939520577
ISSN
1098-5522
DOI
10.1128/IAI.00310-15
language
English
LU publication?
yes
id
3ce29599-72a6-4760-bba4-8af6c1520af4 (old id 7478476)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26099590?dopt=Abstract
date added to LUP
2015-07-09 20:04:19
date last changed
2017-11-05 03:09:20
@article{3ce29599-72a6-4760-bba4-8af6c1520af4,
  abstract     = {Several bacterial species recruit the complement regulators C4b binding protein, Factor H and vitronectin resulting in resistance against the bactericidal activity of human serum. It has recently been demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades C3b and C5. In this study, we found that a series of clinical isolates (n=58) of the respiratory pathogen M. catarrhalis, which is commonly isolated from pre-school children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein (Usp) A2 and A2 hybrid (UspA2H) was identified as the plasminogen-binding factor in the outer membrane proteome of Moraxella. Furthermore, expression of a series of truncated recombinant UspA2 and UspA2H followed by a detailed analysis of protein-protein interactions suggested that the N-terminal head domains bound to the kringle domains of plasminogen. The binding affinity constant (KD) for UspA2(30-539) and UspA2H(50-720) to immobilized plasminogen was 4.8x10(-8) M and 3.13x10(-8) M, respectively, as measured by Biolayer inferometry. Plasminogen bound to intact M. catarrhalis or to recombinant UspA2/A2H was readily accessible for urokinase plasminogen activator that converted the zymogen into active plasmin as verified by the specific substrate S-2251, and a degradation assay comprising fibrinogen. Importantly, plasmin bound at the bacterial surface also degraded C3b and C5 that consequently may contribute to a reduced bacterial killing. Our findings suggest that binding of plasminogen to M. catarrhalis may lead to increased virulence and hence more efficient colonization of the host.},
  author       = {Singh, Birendra and Tamim, Al-Jubair and Voraganti, Chandrashekhar and Andersson, Tobias and Mukherjee, Oindrilla and Su, Yu-Ching and Zipfel, Peter and Riesbeck, Kristian},
  issn         = {1098-5522},
  language     = {eng},
  number       = {9},
  pages        = {3458--3469},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Moraxella catarrhalis binds plasminogen to evade host innate immunity.},
  url          = {http://dx.doi.org/10.1128/IAI.00310-15},
  volume       = {83},
  year         = {2015},
}