Role of Pneumococcal Surface Protein C in Nasopharyngeal Carriage and Pneumonia and Its Ability To Elicit Protection against Carriage of Streptococcus pneumoniae

Abstract

Previous studies suggested that PspC is important in adherence and colonization within the nasopharynx. In this study, we conducted mutational studies to further identify the role PspC plays in the pathogenesis of pneumococci. pspC and/or pspA was insertionally inactivated in a serotype 2 Streptococcus pneumoniae strain and in a serotype 19 S. pneumoniae strain. In the mouse colonization model, pneumococcal strains with mutations in pspC were significantly attenuated in their abilities to colonize. In a mouse pneumonia model, strains with mutations in pspC were unable to infect or multiply within the lung. Using reverse transcriptase PCR we were able to demonstrate that pspC is actively transcribed in vivo, when the bacteria are growing in the nasal cavity and in the lungs. In the bacteremia model, a strain mutated for pspC alone behaved like the wild type, but the absence of both pspC and pspA caused accelerated clearance of the bacteria. Intranasal immunization with PspC with cholera toxin subunit B as an adjuvant protected against intranasal challenge. Evidence was also obtained that revertants that spontaneously acquired PspC expression could multiply and colonize the nasal tissue. This latter finding strongly indicates that pneumococci are actively metabolizing and growing while in the nasopharynx.

Mn 2+ -Dependent Regulation of Multiple Genes in Streptococcus pneumoniae through PsaR and the Resultant Impact on Virulence

“…Female CBA/CAHN-XID/J (CBA/N) mice, 6 to 12 weeks old, were obtained from Jackson Laboratory (Bar Harbor, ME). The virulence of pneumococcal strains in carriage and pneumonia models was examined as previously described (7,11,60). For carriage, mice were inoculated intranasally with 10 7 CFU of EF3030 and EF3030-derived mutants in a 10-l volume.…”

Dual Roles of PspC, a Surface Protein of Streptococcus pneumoniae, in Binding Human Secretory IgA and Factor H

“…The importance of PspC in adherence and colonization of S. pneumoniae to epithelial cells of nasal passages and lungs in mice is well established (8,2). Pneumococcal strains with mutations in PspC are unable to colonize the mucosal surface or infect the lungs.…”

Pneumococcal Adhesins PavB and PspC Are Important for the Interplay with Human Thrombospondin-1

“…The most promising candidates were pneumococcal surface protein C (PspC) and pneumococcal adherence and virulence factor B (PavB). Both proteins possess repeating structures and were previously shown to bind various human extracellular/matricellular matrix proteins such as fibronectin or Vn (11,31), thereby mediating pneumococcal colonization and invasion of host cells (11,(32)(33)(34)(35)(36).…”