Background: S.pyogenes lacking cell-surface M1 protein cannot attach to the nasopharynx yet demonstrates a tropism for the lymphatic niche.
To determine the mechanism that leads to lymphatic tropism we assessed the ability of a naturally derived M negative strain (H584XM), and a recombinant truncated M1 protein (rXM), to bind glycans, which are important structures of the extracellular matrix.
Methods: Binding of full length rM1 protein and rXM was assessed by broad-spectrum glycan screening microarray (672 sequence-defined probes). These proteins were also assessed for their ability to bind glycosaminoglycans (GAGs) in a focused array of 45 GAG related oligosaccharide probes. Whole bacteria (isogenic strains H584, H584XM, and H584∆emm1) were tested for binding to hyaluronan, chondroitin sulfate, and heparin polysaccharides.
Results: The glycan arrays showed stronger binding of rM1 to heparin compared to truncated rXM. rXM did bind to any of the probes included in the GAG array. Binding of whole bacteria to GAGs showed that the M-negative strains H584XM, and H584∆emm1 binding was reduced compared to the parental strain.
The M1-negative strains paradoxically demonstrated enhanced ability to bind high molecular weight hyaluronan compared to the parental M1-positive S.pyogenes strain.
Conclusions: Differential GAG binding related to expression of M protein may contribute to the ability of S.pyogenes to colonise different tissues. Increased capsular hyaluronan, due to mutations affecting expression, results in enhanced interaction with the lymphatic endothelial receptor LYVE-1. Loss of M1 protein leading to binding of hyaluronan represents another mechanism by which S. pyogenes exhibit lymphatic tropism.