nasopharyngeal colonization and invasive disease are enhanced by the cell wall hydrolases lytb and lytc of streptococcus pneumoniae鼻咽的殖民和侵入性疾病是由细胞壁水解酶增强lytb lytc肺炎链球菌.pdfVIP

Nasopharyngeal Colonization and Invasive Disease Are Enhanced by the Cell Wall Hydrolases LytB and LytC of Streptococcus pneumoniae ´ ´ ¤ Elisa Ramos-Sevillano, Miriam Moscoso, Pedro Garcıa, Ernesto Garcıa, Jose Yuste* ´ ´ Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientıficas, and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain Abstract Background: Streptococcus pneumoniae is a common colonizer of the human nasopharynx and one of the major pathogens causing invasive disease worldwide. Dissection of the molecular pathways responsible for colonization, invasion, and evasion of the immune system will provide new targets for antimicrobial or vaccine therapies for this common pathogen. Methodology/Principal Findings: We have constructed mutants lacking the pneumococcal cell wall hydrolases (CWHs) LytB and LytC to investigate the role of these proteins in different phases of the pneumococcal pathogenesis. Our results show that LytB and LytC are involved in the attachment of S. pneumoniae to human nasopharyngeal cells both in vitro and in vivo. The interaction of both proteins with phagocytic cells demonstrated that LytB and LytC act in concert avoiding pneumococcal phagocytosis mediated by neutrophils and alveolar macrophages. Furthermore, C3b deposition was increased on the lytC mutant confirming that LytC is involved in complement evasion. As a result, the lytC mutant showed a reduced ability to successfully cause pneumococcal pneumonia a