De novo formation of focal complex-like structures in host cells by invading Streptococci

Group A streptococcus (GAS) induces its own entry into eukaryotic cells in vitro and in vivo. Fibronectin (Fn) bound to protein F1, a GAS surface prot ein, acts as a bridge connecting the bacterium to host cell integrins. This triggers clustering of integrins, which acquire a polar pattern of distrib ution similar to that of protein F1 on the GAS surface. A unique and transi ent adhesion complex is formed at the site of GAS entry, which does not con tain a-actinin. Vinculin is recruited to the site of GAS entry but is not r equired for uptake. The invading GAS recruits focal adhesion kinase (FAK), which is required for uptake and is tyrosine phosphorylated. The Src kinase s, Src, Yes and Fyn, enhance the efficiency of GAS uptake but are not absol utely required for GAS entry. In addition, Rac and Cdc42, but not Rho, are required for the entry process. We suggest a model in which integrin engage ment by Fri-occupled protein F1 triggers two independent signalling pathway s. One is initiated by FAK recruitment and tyrosine phosphorylation, wherea s the other is initiated by the recruitment and activation of Rac. The two pathways subsequently converge to trigger actin rearrangement leading to ba cterial uptake.