Single
Molecule Force Spectroscopy Reveals Two-Domain
Binding Mode of Pilus‑1 Tip Protein RrgA of <i>Streptococcus
pneumoniae</i> to Fibronectin
- Publication date
- 2018
- Publisher
Abstract
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