Phylogeny of N-Glycolylneuraminic-Acid-Binding Adhesin Domains in the Genus Streptococcus
Objectives: Many oral streptococci bind to sialic acids (Sias) in the human mouth environment via Siglec-like and Unique (SU) domains located within serine-rich repeat protein adhesin binding regions (SRRP-BRs). Our laboratory isolated streptococci from human dental plaque that express SRRP-BRs preferentially binding either the Sia subtype N-acetylneuraminic acid or N-glycolylneuraminic acid (Neu5Gc). The presence of Neu5Gc-preferential binding strains in humans was an unexpected finding because humans are unable to synthesize Neu5Gc. Here, we aim to understand the phylogenetic distribution of such Neu5Gc-preferring strains among streptococci with the goal to obtain clues to their evolutionary origin.
Methods: In a bioinformatic approach, we trained Hidden Markov Models (HMMs) to identify SU domains within SRRP-BRs, and then applied these HMMs to 6,181 publicly available (and 68 unpublished) translated genomes of members of the genus Streptococcus. Among these genomes we identified 446 SU domains that we used to generate a phylogenetic tree to determine the distribution of Neu5Gc-preferring SU domain homologs. To provide insight into structural determinants of Neu5Gc-preferential binding, we solved the crystal structures of two Neu5Gc-preferring SU domains
Results: We identified eleven distinct haplotype sequences, clustered within a subclade of the species Streptococcus sanguinis, that were homologous to the Neu5Gc-preferring SU domains. SU domain sequences showed between 67-97% protein sequence identity and structural similarity with the well-characterized Neu5Gc-preferring S. sanguinis SK36 SrpA SU domain sequence and its experimentally solved crystal structure.
Conclusions: Our data suggest that binding to the nonhuman Sia subtype, Neu5Gc, is specific to certain strains of S. sanguinis. We posit that S. sanguinis may have evolved to bind Neu5Gc as an adaptation to human consumption of a diet that contains animal-derived foods rich in Neu5Gc. Together, these data identify a distinct phenotype of S. sanguinis strains in the human mouth that may be involved in host colonization through binding to a non-host-derived glycan.