Streptococcus sanguinis is a primary colonizer of teeth and is associated with oral health. When it enters the bloodstream, however, this bacterium may cause the serious illness infective endocarditis. The genes required for survival and proliferation in blood have not been identified. The products of these genes could provide a rich source of targets for endocarditis‐specific antibiotics possessing greater efficacy for endocarditis, and also little or no activity against those bacteria that remain in the mouth. We previously created a comprehensive library of S. sanguinis mutants lacking every nonessential gene. We have now screened each member of this library for growth in human serum and discovered 178 mutants with significant abundance changes. The main biological functions disrupted in these mutants, including purine metabolism, were highlighted via network analysis. The components of an ECF‐family transporter were required for growth in serum and were shown for the first time in any bacterium to be essential for endocarditis virulence. We also identified two mutants whose growth was reduced in serum but not in saliva. This strategy promises to enable selective targeting of bacteria based on their location in the body, in this instance, treating or preventing endocarditis while leaving the oral microbiome intact.

中文翻译：

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人血清中血链球菌适应基因的全基因组鉴定及潜在选择性药物靶点的发现

血链球菌是牙齿的主要定植菌，与口腔健康有关。然而，当这种细菌进入血液时，可能会引起严重的疾病——感染性心内膜炎。血液中生存和增殖所需的基因尚未确定。这些基因的产物可以为心内膜炎特异性抗生素提供丰富的靶标来源，这些抗生素对心内膜炎具有更大的功效，而且对口腔中残留的细菌几乎没有或没有活性。我们之前创建了一个缺乏所有非必需基因的血链球菌突变体综合文库。我们现在已经筛选了该文库的每个成员在人血清中的生长情况，发现了 178 个具有显着丰度变化的突变体。通过网络分析强调了这些突变体中被破坏的主要生物功能，包括嘌呤代谢。ECF家族转运蛋白的成分是血清中生长所必需的，并且首次显示在任何细菌中对于心内膜炎毒力都是必需的。我们还鉴定了两种突变体，它们的生长在血清中减少，但在唾液中却没有。该策略有望根据细菌在体内的位置选择性地靶向细菌，在这种情况下，可以治疗或预防心内膜炎，同时保持口腔微生物群完整。