changes in capsular serotype alter the surface exposure of pneumococcal adhesins and impact virulence肺炎球菌荚膜血清型的变化改变了表面接触丰富的毒性和影响.pdfVIP

Changes in Capsular Serotype Alter the Surface Exposure of Pneumococcal Adhesins and Impact Virulence 1. 1. 1 2 2 Carlos J. Sanchez , Cecilia A. Hinojosa , Pooja Shivshankar , Catherine Hyams , Emilie Camberlein , 2 1 Jeremy S. Brown , Carlos J. Orihuela * 1 Department of Microbiology and Immunology, The University of Texas Health Science Center, San Antonio, Texas, United States of America, 2 Department of Medicine, Centre for Respiratory Research, Royal Free and University College Medical School, Rayne Institute, London, United Kingdom Abstract We examined the contribution of serotype on Streptococcus pneumoniae adhesion and virulence during respiratory tract infection using a panel of isogenic TIGR4 (serotype 4) mutants expressing the capsule types 6A (+6A), 7F (+7F) and 23F (+23F) as well as a deleted and restored serotype 4 (+4) control strain. Immunoblots, bacterial capture assays with immobilized antibody, and measurement of mean fluorescent intensity by flow cytometry following incubation of bacteria with antibody, all determined that the surface accessibility, but not total protein levels, of the virulence determinants Pneumococcal surface protein A (PspA), Choline binding protein A (CbpA), and Pneumococcal serine-rich repeat protein (PsrP) changed with serotype. In vitro, bacterial adhesion to Detroit 562 pharyngeal or A549 lung epithelial cells was modestly but significantly altered for +6A, +7F and +23F. In a mouse model of nasopharyngeal colonization, the number of +6A, +7F, and +23F pneumococci in the nasopharynx was reduced 10 to 100-fold versus +4; notably, only m