M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate.

2.50
Hdl Handle:
http://hdl.handle.net/10033/47237
Title:
M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate.
Authors:
Dinkla, K; Cole, J N; Cork, A J; Maamary, P G; McArthur, J D; Chhatwal, G S; Walker, M J
Abstract:
The human protease plasmin plays a crucial role in the capacity of the group A streptococcus (GAS; Streptococcus pyogenes) to initiate invasive disease. The GAS strain NS88.2 was isolated from a case of bacteremia from the Northern Territory of Australia, a region with high rates of GAS invasive disease. Mutagenesis of the NS88.2 plasminogen binding M protein Prp was undertaken to examine the contribution of plasminogen binding and cell surface plasmin acquisition to virulence. The isogenic mutant NS88.2prp was engineered whereby four amino acid residues critical for plasminogen binding were converted to alanine codons in the GAS genome sequence. The mutated residues were reverse complemented to the wild-type sequence to construct GAS strain NS88.2prpRC. In comparison to NS88.2 and NS88.2prpRC, the NS88.2prp mutant exhibited significantly reduced ability to bind human plasminogen and accumulate cell surface plasmin activity during growth in human plasma. Utilizing a humanized plasminogen mouse model of invasive infection, we demonstrate that the capacity to bind plasminogen and accumulate surface plasmin activity plays an essential role in GAS virulence.
Affiliation:
School of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia.
Citation:
M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate. 2008, 22 (8):2715-22 FASEB J.
Journal:
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Issue Date:
Aug-2008
URI:
http://hdl.handle.net/10033/47237
DOI:
10.1096/fj.07-105643
PubMed ID:
18467595
Additional Links:
http://www.fasebj.org/cgi/reprint/22/8/2715
Type:
Article
Language:
en
ISSN:
1530-6860
Appears in Collections:
Publications of Dept. Medizinische Mikrobiologie (MMIK)

Full metadata record

DC FieldValue Language
dc.contributor.authorDinkla, Ken
dc.contributor.authorCole, J Nen
dc.contributor.authorCork, A Jen
dc.contributor.authorMaamary, P Gen
dc.contributor.authorMcArthur, J Den
dc.contributor.authorChhatwal, G Sen
dc.contributor.authorWalker, M Jen
dc.date.accessioned2009-01-09T13:41:47Zen
dc.date.available2009-01-09T13:41:47Zen
dc.date.issued2008-08en
dc.identifier.citationM protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate. 2008, 22 (8):2715-22 FASEB J.en
dc.identifier.issn1530-6860en
dc.identifier.pmid18467595en
dc.identifier.doi10.1096/fj.07-105643en
dc.identifier.urihttp://hdl.handle.net/10033/47237en
dc.description.abstractThe human protease plasmin plays a crucial role in the capacity of the group A streptococcus (GAS; Streptococcus pyogenes) to initiate invasive disease. The GAS strain NS88.2 was isolated from a case of bacteremia from the Northern Territory of Australia, a region with high rates of GAS invasive disease. Mutagenesis of the NS88.2 plasminogen binding M protein Prp was undertaken to examine the contribution of plasminogen binding and cell surface plasmin acquisition to virulence. The isogenic mutant NS88.2prp was engineered whereby four amino acid residues critical for plasminogen binding were converted to alanine codons in the GAS genome sequence. The mutated residues were reverse complemented to the wild-type sequence to construct GAS strain NS88.2prpRC. In comparison to NS88.2 and NS88.2prpRC, the NS88.2prp mutant exhibited significantly reduced ability to bind human plasminogen and accumulate cell surface plasmin activity during growth in human plasma. Utilizing a humanized plasminogen mouse model of invasive infection, we demonstrate that the capacity to bind plasminogen and accumulate surface plasmin activity plays an essential role in GAS virulence.en
dc.language.isoenen
dc.relation.urlhttp://www.fasebj.org/cgi/reprint/22/8/2715en
dc.subject.meshAnimalsen
dc.subject.meshAntigens, Bacterialen
dc.subject.meshBacterial Outer Membrane Proteinsen
dc.subject.meshBase Sequenceen
dc.subject.meshCarrier Proteinsen
dc.subject.meshDNA Primersen
dc.subject.meshDNA, Bacterialen
dc.subject.meshDisease Models, Animalen
dc.subject.meshFibrinogenen
dc.subject.meshGenes, Bacterialen
dc.subject.meshHumansen
dc.subject.meshImmunity, Innateen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Transgenicen
dc.subject.meshMutationen
dc.subject.meshPhagocytosisen
dc.subject.meshPlasminogenen
dc.subject.meshProtein Bindingen
dc.subject.meshRecombinant Proteinsen
dc.subject.meshStreptococcal Infectionsen
dc.subject.meshStreptococcus pyogenesen
dc.subject.meshVirulenceen
dc.titleM protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate.en
dc.typeArticleen
dc.contributor.departmentSchool of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia.en
dc.identifier.journalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biologyen

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