Professor
Guy Tran Van Nhieu
Université Paris Saclay, CNRS UMR9198, INSERM U1080, 91190 Gif-sur-Yvette, France
Title of the talk: Role of bacterial secreted factors with cytotoxic activity towards endothelial cells in pneumococcal meningitis
Abstract
Streptococcus pneumoniae or pneumococcus (PN) is a human nasopharyngeal commensal and major bacterial pathogen responsible for invasive diseases. PN is a major causal agent of bacterial meningitis, with high morbidity and mortality worldwide. Several bacterial virulence determinants have been involved in PN crossing of the blood brain barrier (BBB), but it remains unclear why among the large number of serotypes, a limited subset is more frequently associated with meningitis. We show here that, in contrast to serotype 1 isolates recovered from bacteriemic patients, serotype 1 PN clinical isolates associated with meningitis expressed Pneumococcal Secreted Factors (PSFs) with cytotoxic activity towards in vitro cultured cells. PSF-mediated cytotoxicity was not dependent on the major PN virulence factor pneumolysin and was observed for cultured vascular endothelial cells but not for epithelial cells. PSFs isolated from meningitis causing PN strains causing from serotype 2 and 4 also conferred endothelial cytotoxicity, suggesting their widespread expression in PN meningitis strains. PSF-mediated cytotoxicity was linked to permeabilization of endothelial cell plasma membranes, increase in basal cytosolic Ca2+ levels and disassembly of adherents junctions. Strikingly, PSF cytotoxicity was also associated with a flattening of cell nucleus involving actomyosin contraction. The relevance and perspectives of these findings in PN meningitis will be discussed.
Biography
GTVN has completed his PhD at the age of 26 years from “Pierre and Marie Curie” University, Paris, France and postdoctoral studies from Tufts University School of Medicine. He is the head of the Calcium Signaling and Microbial Infection team, at the I2BC, CNRS-UMR9198-Inserm U1280. He has published more than 102 peer-reviewed articles and has been serving as an editorial board member and editor of the PloS Pathogens and Frontiers in Microbiology Journals