title: Nasopharyngeal colonization and invasive disease are enhanced by the cell wall hydrolases LytB and LytC of Streptococcus pneumoniae.
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.
  
  
  RESULTS
  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 and sepsis. Bacterial mutants lacking both LytB and LytC showed a dramatically impaired attachment to nasopharyngeal cells as well as a marked degree of attenuation in a mouse model of colonization. In addition, C3b deposition and phagocytosis was more efficient for the double lytB lytC mutant and its virulence was greatly impaired in both systemic and pulmonary models of infection.
  
  
  CONCLUSIONS
  This study confirms that the CWHs LytB and LytC of S. pneumoniae are essential virulence factors involved in the colonization of the nasopharynx and in the progress of invasive disease by avoiding host immunity.
authors: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors: Elisa
authors: E
authors: Ramos-Sevillano
authors: Miriam
authors: M
authors: Moscoso
authors: Pedro
authors: P
authors: García
authors: Ernesto
authors: E
authors: García
authors: Jose
authors: J
authors: Yuste
mesh_terms: D000328:Adult; D000818:Animals; D001422:Bacterial Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000201:enzymology*; D015169:Colony Count, Microbial; D003179:Complement C3b / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000382:microbiology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics / Q000378:metabolism*; D009305:Nasopharynx / Q000382:microbiology* / Q000473:pathology*; D009504:Neutrophils / Q000166:cytology; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000150:complications / Q000382:microbiology* / Q000473:pathology; D018805:Sepsis / Q000150:complications / Q000382:microbiology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity
chemical_list: D008565:Membrane Proteins; D003179:Complement C3b; D006867:Hydrolases; C119964:LytB protein, Streptococcus; C419222:LytC protein, Streptococcus; D009238:N-Acetylmuramoyl-L-alanine Amidase