摘要

尽管广泛使用抗生素和疫苗，Streptococcus pneumoniae（肺炎球菌）仍然是人类侵袭和粘膜疾病的持续原因。这种生物的弹性是由于它通过吸收和结合来自周围微生物群落的新遗传物质而适应的能力。DNA吸收和重组是由紧密调节的群体感应系统控制的，这是由能力刺激肽（CSP）的胞外积累触发的。在这项研究中，我们证明CSP可以刺激不同的BLP细菌素阵列的生产。这种交叉刺激通过增加细菌素信息素BLPC的产生和分泌而发生，并且需要功能能力调节系统。我们表明，在操纵子编码BLPC及其转运子的启动子中高度保守的基序介导CSP上调。CSP刺激后BLPC的积累导致整个BLP位点的激活增强。利用生物膜生长的生物体作为粘膜表面上竞争和遗传交换的模型，我们证明了细菌素分泌增强了DNA交换，表明具有能力的细菌素的共同刺激提供了适应性优势。BLP和COM的调节途径被认为是分化的，并且专门用于肺炎球菌的远缘祖先。尽管如此，这两个系统保持了一个监管连接，促进竞争和适应的目标是裂解广泛的潜在竞争对手，同时提供的手段纳入他们的DNA。

Streptococcus pneumoniae (pneumococcus) has remained a persistent cause of invasive and mucosal disease in humans despite the widespread use of antibiotics and vaccines. The resilience of this organism is due to its capacity for adaptation through the uptake and incorporation of new genetic material from the surrounding microbial community. DNA uptake and recombination is controlled by a tightly regulated quorum sensing system that is triggered by the extracellular accumulation of competence stimulating peptide (CSP). In this study, we demonstrate that CSP can stimulate the production of a diverse array of blp bacteriocins. This cross stimulation occurs through increased production and secretion of the bacteriocin pheromone, BlpC, and requires a functional competence regulatory system. We show that a highly conserved motif in the promoter of the operon encoding BlpC and its transporter mediates the upregulation by CSP. The accumulation of BlpC following CSP stimulation results in augmented activation of the entire blp locus. Using biofilm-grown organisms as a model for competition and genetic exchange on the mucosal surface, we demonstrate that DNA exchange is enhanced by bacteriocin secretion suggesting that co-stimulation of bacteriocins with competence provides an adaptive advantage. The blp and com regulatory pathways are believed to have diverged and specialized in a remote ancestor of pneumococcus. Despite this, the two systems have maintained a regulatory connection that promotes competition and adaptation by targeting for lysis a wide array of potential competitors while simultaneously providing the means for incorporation of their DNA.

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005413