title: PavA of Streptococcus pneumoniae modulates adherence, invasion, and meningeal inflammation.
abstract: Pneumococcal adherence and virulence factor A (PavA) is displayed to the cell outer surface of Streptococcus pneumoniae and mediates pneumococcal binding to immobilized fibronectin. PavA, which lacks a typical gram-positive signal sequence and cell surface anchorage motif, is essential for pneumococcal virulence in a mouse infection model of septicemia. In this report the impact of PavA on pneumococcal adhesion to and invasion of eukaryotic cells and on experimental pneumococcal meningitis was investigated. In the experimental mouse meningitis model, the virulence of the pavA knockout mutant of S. pneumoniae D39, which did not show alterations of subcellular structures as indicated by electron microscopic studies, was strongly decreased. Pneumococcal strains deficient in PavA showed substantially reduced adherence to and internalization of epithelial cell lines A549 and HEp-2. Similar results were obtained with human brain-derived microvascular endothelial cells and human umbilical vein-derived endothelial cells. Attachment and internalization of pneumococci were not significantly affected by preincubation or cocultivations of pneumococci with anti-PavA antisera. Pneumococcal adherence was also not significantly affected by the addition of PavA protein. Complementation of the pavA knockout strain with exogenously added PavA polypeptide did not restore adherence of the mutant. These data suggest that PavA affects pneumococcal colonization by modulating expression or function of important virulence determinants of S. pneumoniae.
authors.affiliation: Research Center for Infectious Diseases, University of Würzburg, Röntgenring 11, D-97070 Würzburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pracht
authors.forename: Christine
authors.initials: C
authors.lastname: Elm
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerber
authors.forename: Simone
authors.initials: S
authors.lastname: Bergmann
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Marleen
authors.initials: M
authors.lastname: Seiler
authors.forename: Kwang S
authors.initials: KS
authors.lastname: Kim
authors.forename: Howard F
authors.initials: HF
authors.lastname: Jenkinson
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004285:Dogs; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; C500900:PavA protein, Streptococcus pneumoniae; C078635:fibronectin-binding proteins, bacterial