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Infection and Immunity, May 2005, p. 2680-2689, Vol. 73, No. 5
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.5.2680-2689.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Christine Elm,1,
Joachim Gerber,2
Simone Bergmann,1
Manfred Rohde,3
Marleen Seiler,3
Kwang S. Kim,4
Howard F. Jenkinson,5
Roland Nau,2 and
Sven Hammerschmidt1*
Research Center for Infectious Diseases, University of Würzburg, Würzburg, Germany,1 Department of Neurology, University of Göttingen, Göttingen, Germany,2 GBF-German Research Centre for Biotechnology, Braunschweig, Germany,3 Department of Pediatric Infectious Diseases, John Hopkins University School of Medicine, Baltimore, Maryland,4 Department of Oral and Dental Science, University of Bristol, Bristol, United Kingdom5
Received 22 June 2004/ Returned for modification 29 July 2004/ Accepted 4 January 2005
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.
These authors contributed equally to the results.
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