Publications

Serine-rich repeat glycoproteins are adhesins expressed by commensal and pathogenic Gram-positive bacteria. A subset of these adhesins, expressed by oral streptococci, binds sialylated glycans decorating human salivary mucin MG2/MUC7, and platelet glycoprotein GPIb. Specific sialoglycan targets were previously identified for the ligand-binding regions (BRs) of GspB and Hsa, two serine-rich repeat glycoproteins expressed by Streptococcus gordonii While GspB selectively binds sialyl-T antigen, Hsa displays broader specificity. Here we examine the binding properties of four additional BRs from Streptococcus sanguinis or Streptococcus mitis and characterize the molecular determinants of ligand selectivity and affinity. Each BR has two domains that are essential for sialoglycan binding by GspB. One domain is structurally similar to the glycan-binding module of mammalian Siglecs (sialic acid-binding immunoglobulin-like lectins), including an arginine residue that is critical for glycan recognition, and that resides within a novel, conserved YTRY motif. Despite low sequence similarity to GspB, one of the BRs selectively binds sialyl-T antigen. Although the other three BRs are highly similar to Hsa, each displayed a unique ligand repertoire, including differential recognition of sialyl Lewis antigens and sulfated glycans. These differences in glycan selectivity were closely associated with differential binding to salivary and platelet glycoproteins. Specificity of sialoglycan adherence is likely an evolving trait that may influence the propensity of streptococci expressing Siglec-like adhesins to cause infective endocarditis.

This review of tuberculosis epidemiology is intended to provide a historical perspective on the public health approach to tuberculosis (TB) control in California. This historical context offers a lens through which to view current epidemiologic trends and insight into how new therapeutic tools can be applied. Since 1993, the year detailed case reporting was instituted, California has had a decrease in recent TB transmission as evidenced by a reduction in pediatric cases and an increased percentage of cases attributable to progression of latent infection to TB disease in the foreign-born population. Overall, there has been a dramatic decline in the annual TB case count, but the speed of the decline has slowed over the last several years. At the current pace and case count of 2137 in 2015, California will not achieve TB elimination (<1 TB case per one million population) for at least 100 years. There are an estimated 2.1 million persons in California with latent TB infection. Modeling suggests that LTBI detection and treatment are important in reaching TB elimination. For this reason, a coalition of stakeholders in California is exploring novel approaches to accelerate the case decline in order to prevent unnecessary disease and death.