Scl1-dependent internalization of group A Streptococcus via direct interactions with the alpha2beta(1) integrin enhances pathogen survival and re-emergence.
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 alpha(2)beta(1). Here, we investigate whether the same Scl1 variant expressed by GAS cells interacts with the integrin alpha2beta(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 alpha2beta(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-alpha2 integrin-subunit antibody and type I collagen, (iii) recombinant alpha2-I domain bound the wild-type GAS cells and (iv) internalization of wild-type cells was significantly increased in C2C12 cells expressing the alpha2beta(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.
Caswell
Clayton C
CC
Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506, USA.
Lukomska
Ewa
E
Seo
Neung-Seon
NS
Höök
Magnus
M
Lukomski
Slawomir
S
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D015169:Colony Count, Microbial; D006801:Humans; D038982:Integrin alpha2beta1 / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013297:Streptococcus pyogenes / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*
D001426:Bacterial Proteins; D038982:Integrin alpha2beta1; D003094:Collagen