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Scl1‐dependent internalization of group A Streptococcus via direct interactions with the α 2 β 1 integrin enhances pathogen survival and re‐emergence
Author(s) -
Caswell Clayton C.,
Lukomska Ewa,
Seo NeungSeon,
Höök Magnus,
Lukomski Slawomir
Publication year - 2007
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2007.05741.x
Subject(s) - internalization , integrin , biology , streptococcus pyogenes , recombinant dna , microbiology and biotechnology , collagen receptor , pathogen , receptor , wild type , protein subunit , mutant , biochemistry , genetics , bacteria , gene , staphylococcus aureus
Summary 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 α 2 β 1 . Here, we investigate whether the same Scl1 variant expressed by GAS cells interacts with the integrin α 2 β 1 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 α 2 β 1 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‐α 2 integrin‐subunit antibody and type I collagen, (iii) recombinant α 2 ‐I domain bound the wild‐type GAS cells and (iv) internalization of wild‐type cells was significantly increased in C2C12 cells expressing the α 2 β 1 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.