Abstract：
Competence development in the human pathogen Streptococcus pneumoniae controls several features such as genetic transformation, biofilm formation, and virulence. Competent bacteria produce so-called \"fratricins\" such as CbpD that kill noncompetent siblings by cleaving peptidoglycan (PGN). CbpD is a choline-binding protein (CBP) that binds to phosphorylcholine residues found on wall and lipoteichoic acids (WTA and LTA) that together with PGN are major constituents of the pneumococcal cell wall. Competent pneumococci are protected against fratricide by producing the immunity protein ComM. How competence and fratricide contribute to virulence is unknown. Here, using a genome-wide CRISPRi-seq screen, we show that genes involved in teichoic acid (TA) biosynthesis are essential during competence. We demonstrate that LytR is the major enzyme mediating the final step in WTA formation, and that, together with ComM, is essential for immunity against CbpD. Importantly, we show that key virulence factors PspA and PspC become more surface-exposed at midcell during competence, in a CbpD-dependent manner. Together, our work supports a model in which activation of competence is crucial for host adherence by increased surface exposure of its various CBPs.
摘要：
人类病原体肺炎链球菌的能力发展控制着几个特征，如遗传转化，生物膜的形成，和毒力。感受态细菌产生所谓的“fraticins”，例如CbpD，通过切割肽聚糖（PGN）杀死无能力的兄弟姐妹。CbpD是一种胆碱结合蛋白（CBP），可与壁上发现的磷酰胆碱残基结合，并与PGN一起是肺炎球菌细胞壁的主要成分。通过产生免疫蛋白ComM来保护感受态肺炎球菌免受自杀。能力和自相残杀对毒力的贡献尚不清楚。这里,使用全基因组CRISPRi-seq筛选，我们表明，参与磷壁酸（TA）生物合成的基因在能力过程中是必不可少的。我们证明LytR是介导WTA形成最后一步的主要酶，而且，与ComM一起，对CbpD的免疫力至关重要。重要的是,我们表明，关键毒力因子PspA和PspC在能力过程中在中细胞表面暴露更多，以CbpD依赖的方式。一起,我们的工作支持了一个模型,在该模型中,通过增加其各种CBPs的表面暴露,激活能力对于宿主粘附至关重要.
