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: 

O-acetylation of the serine-rich repeat glycoprotein GspB is coordinated with accessory Sec transport.

PLoS pathogens

Seepersaud R, Sychantha D, Bensing BA, Clarke AJ, Sullam PM

Evaluation of daptomycin combinations with cephalosporins or gentamicin against Streptococcus mitis group strains in an in vitro model of simulated endocardial vegetations (SEVs).

The Journal of antimicrobial chemotherapy

Yim J, Smith JR, Singh NB, Rice S, Stamper K, Garcia de la Maria C, Bayer AS, Mishra NN, Miró JM, Tran TT, Arias CA, Sullam P, Rybak MJ

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis.

Antimicrobial agents and chemotherapy

Garcia-de-la-Maria C, Xiong YQ, Pericas JM, Armero Y, Moreno A, Mishra NN, Rybak MJ, Tran TT, Arias CA, Sullam PM, Bayer AS, Miro JM

Perturbations of Phosphatidate Cytidylyltransferase (CdsA) Mediate Daptomycin Resistance in Streptococcus mitis/oralis by a Novel Mechanism.

Antimicrobial agents and chemotherapy

Mishra NN, Tran TT, Seepersaud R, Garcia-de-la-Maria C, Faull K, Yoon A, Proctor R, Miro JM, Rybak MJ, Bayer AS, Arias CA, Sullam PM

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