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Proteolytic processing of the streptococcal IgG cleaving enzyme IdeS reduces immunorecognition without affecting the biological activity of the enzyme
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-54050OAI: oai:DiVA.org:umu-54050DiVA, id: diva2:515377
Tilgjengelig fra: 2012-04-12 Laget: 2012-04-12 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Inngår i avhandling
1. The streptococcal IgG degrading enzyme IdeS: studies on host-pathogen interactions
Åpne denne publikasjonen i ny fane eller vindu >>The streptococcal IgG degrading enzyme IdeS: studies on host-pathogen interactions
2012 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The important human pathogen Streptococcus pyogenes causes both mild infections such as pharyngitis and impetigo but also severe life threatening invasive infections.  Specific antibodies (IgG) recognize pathogens and are important mediators for pathogen clearance by the immune defence. S.ipyogenes expresses a highly effective and specific IgG endopeptidase called IdeS (immunoglobulin degrading enzyme of S.ipyogenes). IdeS rescues bacteria from opsonising IgG by cleavage of IgG generating two fragments F(ab´)2 and ½Fc. Moreover, IdeS block ROS production by neutrophils. In this thesis I have studied (i) allelic variants of IdeS and their biological potential, (ii) consequences of ½Fc production for host-pathogen interactions and (iii) IdeS processing by streptococcal and neutrophil proteases.

When investigating the allelic variants of IdeS we could show that in respect to IgG degradation and inhibition of ROS production the allelic variants where indistinguishable, however the allelic variant of serotype M28 appears to be an unique exception as this protein was deficient in IgG cleavage but still inhibited ROS production. Further, the ½Fc fragments produced when IgG is cleaved by IdeS were shown to prime human neutrophils and under ex vivo experimental conditions this increased the bactericidal activity of the neutrophils. Finally, we made the interesting finding that IdeS is N-terminally processed by neutrophil proteases and by the streptococcal protease SpeB, but retain enzymatic activity and was less immunogenic compared to the full length protein.

sted, utgiver, år, opplag, sider
Umeå: Umeå universitet, 2012. s. 43
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1491
Emneord
streptococcus pyogenes, IdeS
HSV kategori
Forskningsprogram
molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-53706 (URN)978-91-7459-404-1 (ISBN)
Disputas
2012-05-03, Bergasalen, NUS By 27, Umeå, 10:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2012-04-12 Laget: 2012-04-04 Sist oppdatert: 2018-06-08bibliografisk kontrollert

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Persson, HelenaJohansson Söderberg, JennyVindebro, Reinevon Pawel-Rammingen, Ulrich

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