The Siglec-like Serine-Rich Repeat (SRR) adhesins mediate bacterial attachment to mammalian hosts via sialoglycan receptors. Here, we combine structural, computational, biochemical, and phylogenetic approaches to elucidate the determinants of the sialoglycan-binding spectrum across the family of Siglec-like SRR adhesins. We further identified mutable positions that disproportionately affect sialoglycan selectivity, as demonstrated by increases in binding to alternative ligands of 2- to 3- orders of magnitude. Biologically, these studies highlight how bacteria nimbly modulate the receptor interaction during coevolution of host and pathogen. These studies additionally created binding proteins specific for sialyl-T antigen or 6S-sialyl LewisX that can recognize glycosylation of human plasma proteins. The engineered binding proteins can facilitate the characterization of normal cellular glycan modifications or may be used as diagnostic tools in disease states with altered glycosylation.

Selectivity and engineering of the sialoglycan-binding spectrum in Siglec-like adhesins