Summary: | 碩士 === 國防醫學院 === 微生物及免疫學研究所 === 101 === Streptococcus pneumoniae is a common respiratory pathogen leading to community-acquired pneumonia. Inflammation is often activated to clear pulmonary bacteria without damaging the lung architecture. However, increased incidence of pneumococcal infections complicated by an empyema, and/or fibrinopurulent stage progression is reported in recent years. The pathogenesis is still elusive. Phosphorylcholine, an unusual structural feature in prokaryotes, resides predominant in cell wall and cytoplasmic membrane among many respiratory pathogens. It mediates colonization, autolysis, natural transformation and antimicrobial peptide resistance. Glycerophosphodiester phosphodiesterase (GlpQ) metabolizes glycerophosphorylcholine from lung epithelial cells to produce free choline that turns into phosphorylcholine and is incorporated into bacterial surface by lic operon. Two orthologs of glpQ genes in S. pneumoniae are found. The membrane motif-containing glpQ is universal present in S. pneumoniae strains. The other form, glpQ2 which is structurally relative to glpQ in H. influenzae and M. pneumoniae, is sporadic present in some S. pneumoniae strains with serotypes 19A and 3 that are frequently associated with complicated pneumonia these years. In this study, we address the pathophysiological role of glpQ2 in complicated pneumonia-causing strains. We constructed glpQ2 mutant in CGMH836 which was isolated from pediatric patient suffering from complicated pneumonia. Deficiency of glpQ2 revealed lowered ChoP expression on surface. Significantly reduced autolytic ability and transformation efficiency were also examined. glpQ2 mutant revealed reduced adherence and cytotoxicity toward human lung epithelial cell lines, A549 and BEAS2B. In contrast, complementation strains restored to be indistinguishable compared with wild type strain. In respiratory infection murine model, glpQ2 was indispensable for nasopharyngeal and lung colonization. Our findings suggest that glpQ2 confers choline metabolism and contributes to pathogenesis via promotion of adherence and cytotoxicity to host cells. However, the pathogenesis of glpQ2 in complicated pneumonia is still remained to be investigated.
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