For host cell adhesion and invasion, surface piliation procures benefits for bacteria. A detailed investigation of how pili adhere to host cells is therefore a key aspect in understanding their role during infection. <i>Streptococcus pneumoniae</i> TIGR 4, a clinical relevant serotype 4 strain, is capable of expressing pilus-1 with terminal RrgA, an adhesin interacting with host extracellular matrix (ECM) proteins. We used single molecule force spectroscopy to investigate the binding of full-length RrgA and single RrgA domains to fibronectin. Our results show that full-length RrgA and its terminal domains D3 and D4 bind to fibronectin with forces of 51.6 (full length), 52.8 (D3), and 46.2 pN (D4) at force-loading rates of around 1500 pN/s. Selective saturation of D3 and D4 binding sites on fibronectin showed that both domains can interact simultaneously with fibronectin, revealing a two-domain binding mechanism for the pilus-1 tip protein. The high off rates and the corresponding short lifetime of the RrgA Fn bond (τ = 0.26 s) may enable piliated pneumococci to form and maintain a transient contact to fibronectin-containing host surfaces and thus to efficiently scan the surface for specific receptors promoting host cell adhesion and invasion. These molecular properties could be essential for <i>S. pneumoniae</i> pili to mediate initial contact to the host cells andshared with other piliated Gram-positive bacteriafavor host invasion
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