The Mechanism of PblB Contribute to Pneumococcal Colonization and Pneumonia

Streptococcus pneumoniae is a dangerous pathogen, causing a multitude of serious and life-threatening diseases around the globe. Capsule is thought to be a major virulence factor of S. pneumoniae. However, several clinical studies have shown that bacterial clones belonging to the same serotypes had distinct abilities to cause disease. Properties associated with a particular clonal type, in addition to capsular type, are considered important for the potential of pneumococci to cause disease. It is known that certain clones of S. pneumoniae suceessfully disseminate in some regions or worldwide. Clonal success of S. pneumoniae was not solely due to antibiotic resistance, as evidenced by the dissemination of non-antibiotic resistant clones. It is thought that genetic factors other than antibiotic resistance also contribute to clonal success. In general, the reason for clonal sucess is not completely understood. In Taiwan, pneumonia was the most common disease type of invasive pneumococcal disease in children. Since 1997, there has been an increase of necrotizing pneumonia and empyema caused by S. pneumoniae in children in Taiwan. Before the introduction of 7-valent pneumococcal conjugate vaccine in 2005, serotype 14 was the predominant type causing pneumonia. Among strains of serotype 14 causing pneumonia, sequence type (ST) 46 was the most prevalent clone. The serotype 14 ST46 clone accounted for 15% to 35% of the strains causing culture-confirmed pneumococcal pneumonia among children in Taiwan. In our previous study, we constructed a microarray based on the genome of this endemic, multi-resistant serotype 14 ST46 clone. We identified pblB, a phage-encoded virulence factor implicated (in Streptococcus mitis) in infective endocarditis, as a genetic factor that contributes to pneumococcal colonization and pneumonia in mice. PblB involved in adhesion of S. pneumoniae to lung epithelial cell (A549 cells). Whether PblB is directly involved in adhesion or merely participates in this process by modulating the expression of “true” adhesins is not known. The aims of the present project are to study the prevalence of PblB among other clinical isolates and the function of PblB. PblB will be expressed to perform competitive inhibition binding assay; PblB antiserum also will be generated to perform antibody inhibition assay to investigate if PblB is an adhesin. On the basis of its amino acid sequence, PblB is predicted to form a signal-peptide, a coiled-coil region, 3 internal repeats, and a galactose-binding domain. Whether PblB mediate adhesion through binding galactose on the respiratory epithelial cell will be investigated. We will study if PblB has other function involving in biofilm formation and anti-phagocytosis ability. Finally, we investigate whether antibody against PblB can protect against pneumococcal challenge in mice to be a target for future vaccine design. This study provides an example of how the S. pneumoniae accessory genome might be influencing the epidemiology of pneumococcal disease.

Project ID:PC10308-1813
External Project ID:MOST103-2314-B182-023