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dc.contributor.authorHovingh, Elise S
dc.contributor.authorvan den Broek, Bryan
dc.contributor.authorKuipers, Betsy
dc.contributor.authorPinelli, Elena
dc.contributor.authorRooijakkers, Suzan H M
dc.contributor.authorJongerius, Ilse
dc.date.accessioned2018-01-09T09:21:41Z
dc.date.available2018-01-09T09:21:41Z
dc.date.issued2017-07
dc.identifier.citationAcquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface. 2017, 13 (7):e1006531 PLoS Pathog.en
dc.identifier.issn1553-7374
dc.identifier.pmid28742139
dc.identifier.doi10.1371/journal.ppat.1006531
dc.identifier.urihttp://hdl.handle.net/10029/621044
dc.description.abstractWhooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis.
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen
dc.subject.meshBacterial Proteins
dc.subject.meshBordetella pertussis
dc.subject.meshComplement C1
dc.subject.meshComplement C2
dc.subject.meshComplement C4
dc.subject.meshHumans
dc.subject.meshVirulence
dc.subject.meshVirulence Factors, Bordetella
dc.subject.meshWhooping Cough
dc.titleAcquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface.en
dc.typeArticleen
dc.identifier.journalPlos Pathog 2017, 13(7):e1006531en
html.description.abstractWhooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis.


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