Paul Sullam, MD

Professor
Department of Medicine - Infectious Disease
+1 415 221-4810 ext. 2550

The focus of my laboratory is the pathogenesis of endovascular infections due to Gram-positive bacteria. We are currently examining the mechanisms by which staphylococci and streptococci bind to human platelets, and how this interaction contributes to the pathogenesis of infective endocarditis. The binding of bacteria to platelets is likely to be important for the initial colonization of the endovascular surface, and for the subsequent formation of macroscopic endocardial lesions. In addition, platelet-bacterium binding may facilitate the dissemination of infection to extra-cardiac sites.

Our studies indicate that these organisms can bind to platelets by a variety of bacterial surface components, and that each species is likely to express multiple adhesins. For example,Streptococcus mitis appears to bind platelets in part by several surface proteins that are encoded by a lysogenic bacteriophage.  Our current work in this area focuses on defining the structural basis for binding by these adhesins, and identifying their receptors.   Platelet binding by Streptococcus gordonii is mediated partially by a large, serine-rich surface protein (GspB). Of note, the gene encoding GspB is part of an operon containing homologs of the Sec system that are essential for GspB export. We are now in the process of characterizing further these and other possible adhesins, as well as their binding sites on the platelet membrane.  This work includes solving the crystal structure of GspB and related adhesins, defining how they bind their host carbohydrate targets, and determining the impact of shear forces on binding.  Because serine rich homologs of GspB was widely prevalent in a broad range of Gram-positive pathogens, these studies are applicable to infections beyond endocarditis, such as pneumonia and meningitis.

Primary Thematic Area: 
Virology & Microbial Pathogenesis
Secondary Thematic Area: 
None
Research Summary: 
Pathogenetic mechanisms of Gram-positive pathogens
Publications: 

Structures of the Streptococcus sanguinis SrpA Binding Region with Human Sialoglycans Suggest Features of the Physiological Ligand.

Biochemistry

Loukachevitch LV, Bensing BA, Yu H, Zeng J, Chen X, Sullam PM, Iverson TM

Novel aspects of sialoglycan recognition by the Siglec-like domains of streptococcal SRR glycoproteins.

Glycobiology

Bensing BA, Khedri Z, Deng L, Yu H, Prakobphol A, Fisher SJ, Chen X, Iverson TM, Varki A, Sullam PM

Mechanism of a cytosolic O-glycosyltransferase essential for the synthesis of a bacterial adhesion protein.

Proceedings of the National Academy of Sciences of the United States of America

Chen Y, Seepersaud R, Bensing BA, Sullam PM, Rapoport TA

Structural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin.

The Journal of biological chemistry

Bensing BA, Loukachevitch LV, McCulloch KM, Yu H, Vann KR, Wawrzak Z, Anderson S, Chen X, Sullam PM, Iverson TM

Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood.

PLoS pathogens

Deng L, Bensing BA, Thamadilok S, Yu H, Lau K, Chen X, Ruhl S, Sullam PM, Varki A