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Evasion of phagocyt...
Evasion of phagocytosis through cooperation between two ligand-binding regions in Streptococcus pyogenes M protein.
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- Carlsson, Fredric (author)
- Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine
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- Berggård, Karin (author)
- Lund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Stålhammar-Carlemalm, Margaretha (author)
- Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine
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- Lindahl, Gunnar (author)
- Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- 2003-09-29
- 2003
- English.
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 198:7, s. 1057-1068
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Abstract
Subject headings
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- The M protein of Streptococcus pyogenes is a major bacterial virulence factor that confers resistance to phagocytosis. To analyze how M protein allows evasion of phagocytosis, we used the M22 protein, which has features typical of many M proteins and has two well-characterized regions binding human plasma proteins: the hypervariable NH2-terminal region binds C4b-binding protein (C4BP), which inhibits the classical pathway of complement activation; and an adjacent semivariable region binds IgA-Fc. Characterization of chromosomal S. pyogenes mutants demonstrated that each of the ligand-binding regions contributed to phagocytosis resistance, which could be fully explained as cooperation between the two regions. Deposition of complement on S. pyogenes occurred almost exclusively via the classical pathway, even under nonimmune conditions, but was down-regulated by bacteria-bound C4BP, providing an explanation for the ability of bound C4BP to inhibit phagocytosis. Different opsonizing antisera shared the ability to block binding of both C4BP and IgA, suggesting that the two regions in M22 play important roles also under immune conditions, as targets for protective antibodies. These data indicate that M22 and similar M proteins confer resistance to phagocytosis through ability to bind two components of the human immune system.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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