Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, 565-0871, Japan.
Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, Suita, Osaka, 565-0871, Japan.
Commun Biol. 2019 Mar 8;2:96. doi: 10.1038/s42003-019-0340-7. eCollection 2019.
Evolutionarily conserved virulence factors can be candidate therapeutic targets or vaccine antigens. Here, we investigated the evolutionary selective pressures on 16 pneumococcal choline-binding cell-surface proteins since is one of the pathogens posing the greatest threats to human health. Phylogenetic and molecular analyses revealed that had the highest codon rates to total numbers of codons under considerable negative selection among those examined. Our in vitro and in vivo assays indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing. Deficiency of under relaxed selective pressure also caused a similar tendency but showed no significant difference in mouse intranasal infection. Thus, molecular evolutionary analysis is a powerful tool that reveals the importance of virulence factors in real-world infection and transmission, since calculations are performed based on bacterial genome diversity following transmission of infection in an uncontrolled population.
进化上保守的毒力因子可以成为治疗靶点或疫苗抗原的候选物。在这里，我们研究了 16 种肺炎球菌胆碱结合细胞表面蛋白的进化选择压力，因为 是对人类健康构成最大威胁的病原体之一。系统发育和分子分析表明，在研究的所有基因中， 的密码子使用最高，表明其受到很强的负选择。我们的体外和体内实验表明，CbpJ 通过逃避中性粒细胞的杀伤作用，在肺炎球菌肺炎中作为一种毒力因子发挥作用。在放松选择压力的情况下， 的缺失也导致了类似的趋势，但在小鼠鼻腔感染模型中没有显著差异。因此，分子进化分析是一种强大的工具，它揭示了毒力因子在实际感染和传播中的重要性，因为计算是基于感染在不受控制的人群中传播后细菌基因组多样性进行的。
