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Membrane cofactor protein (CD46) binding to clinical isolates of Streptococcus pyogenes: binding to M type 18 strains is independent of Emm or Enn proteins

Abstract number: 1732_56

Oliver M., Feito M., Sánchez A., Pérez D., Rodríguez de Cordoba S., Albertí S., Rojo J.

Previous studies have shown that Membrane cofactor protein (MCP) CD46 is the cellular receptor of keratinocytes for S. pyogenes of the M types M6, M5 and M22. However, data using other M types and cells have cast some doubts on the role of CD46 as the main receptor for S. pyogenes in all human cells.

Objective: The aim of the present study was to analyse the binding of CD46 to clinical isolates of S. pyogenes of different M types.

Methods: Twenty six S. pyogenes clinical isolates from different origins and expressing different M types were included in this study. To investigate the role of the hyaluronic acid capsule, the Emm18 protein and the Enn18 protein, we used a set of mutants derived from the wild type strain 87–282 including the Emm18 protein deficient mutant 282KZ and the capsule deficient mutant TX72. Isogenic mutants TX74 and TX76, derived from TX72, deficient in the Emm18 protein and the Enn18 protein, respectively, were also included in the study.

Binding of CD46 was determined by incubation of the bacteria with purified recombinant soluble human CD46. CD46 binding to each strain was determined by Western blot analysis using policlonal anti-CD46 antibodies. Binding of CD46 to purified recombinant Emm18 protein was determined by ELISA.

Results: Binding assays showed that CD46 binding to S. pyogenes was highly variable among the 17 different M types tested, being M type 18 strains among those showing the strongest binding. The binding of purified human CD46 to M type 18 strains was independent of the expression of the hyaluronic acid capsule, since the highly mucoid strain 87–282 bound CD46 as efficiently as the derived capsule deficient mutant TX72.

Surprisingly, the Emm18 protein deficient mutants 282-KZ and TX74 bound CD46. Moreover, CD46 did not bind to purified recombinant Emm18 constructs, suggesting that the Emm18 protein is not involved in the binding of CD46 to the M type 18 strains. To test another protein candidate for CD46 binding to S. pyogenes M type 18, we generated the strain TX76. TX76 bound CD46 as efficiently as the strains TX72 and TX74.

Conclusion: Binding of human CD46 to S. pyogenes is highly heterogeneous and do not depend on the presence of hyaluronic acid capsule. Despite Emm proteins have been assumed to mediate binding of S. pyogenes to CD46, M type18 strains bind CD46 very efficiently through a cell surface protein different from the Emm and Enn proteins.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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