Scl1-dependent internalization of group A Streptococcus via direct interactions with the α2β1 integrin enhances pathogen survival and re-emergence

Clayton C. Caswell, Ewa Lukomska, Neung Seon Seo, Magnus Höök, Slawomir Lukomski

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The molecular pathogenesis of infections caused by group A Streptococcus (GAS) is not fully understood. We recently reported that a recombinant protein derived from the collagen-like surface protein, Scl1, bound to the human collagen receptor, integrin α2β1. Here, we investigate whether the same Scl1 variant expressed by GAS cells interacts with the integrin α2β1 and affects the biological outcome of host-pathogen interactions. We demonstrate that GAS adherence and internalization involve direct interactions between surface expressed Scl1 and the α2β1 integrin, because (i) both adherence and internalization of the scl1-inactivated mutant were significantly decreased, and were restored by in-trans complementation of Scl1 expression, (ii) GAS internalization was reduced by pre-treatment of HEp-2 cells with anti-α2 integrin-subunit antibody and type I collagen, (iii) recombinant α2-I domain bound the wild-type GAS cells and (iv) internalization of wild-type cells was significantly increased in C2C12 cells expressing the α2β1 integrin as the only collagen-binding integrin. Next, we determined that internalized GAS re-emerges from epithelial cells into the extracellular environment. Taken together, our data describe a new molecular mechanism used by GAS involving the direct interaction between Scl1 and integrins, which increases the overall capability of the pathogen to survive and re-emerge.

Original languageEnglish (US)
Pages (from-to)1319-1331
Number of pages13
JournalMolecular Microbiology
Volume64
Issue number5
DOIs
StatePublished - Jun 2007

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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