摘要

在人鼻咽部定殖期间，多种革兰氏阳性病原体肺炎链球菌菌株共存并使用称为细菌素的分泌型抗微生物肽彼此竞争。主要的肺炎球菌细菌素由blp操纵子编码，其转录受控于群体感应（QS）多肽家族的分泌和检测。我们检测了4,096个肺炎球菌基因组中blp QS信号（BlpC）和受体（BlpH）之间的基因组关联。9个QS信号肽类型与5个系统发育相关QS受体组之间的不完全一致表明，信号（其中细胞产生非克隆细胞可以检测到的信号）和窃听（其中细胞响应于它们不产生的信号）之间的广泛串扰。为了测试这些可能性，我们量化了含有六种不同blp QS受体变体中的每一种的报道菌株对同源和非同源合成肽信号的反应。正如预测的那样，我们发现了六个测试信号中的五个串扰以及四个这些受体中的窃听的证据。这些体外结果在彼此相邻生长的肺炎球菌菌落之间的相互作用期间得到证实，这提供了直接证据表明串扰和窃听发生在内源性，生态相关的信号分泌水平。最后，使用空间显式随机模型，我们显示窃听基因型在株间竞争中获得进化优势，即使它们对非同源信号的亲和力低至与同源信号的亲和力的10％。我们的研究结果强调了社会互动在介导细菌内部特异性竞争中的重要性，并阐明了QS系统中多态性可以介导多种竞争性相互作用。

During colonization of the human nasopharynx, multiple strains of the Gram-positive pathogen Streptococcus pneumoniae coexist and compete with each other using secreted antimicrobial peptides called bacteriocins. The major class of pneumococcal bacteriocins is encoded by the blp operon, whose transcription is controlled by the secretion and detection of a polymorphic family of quorum sensing (QS) peptides. We examined the genomic association between blp QS signals (BlpC) and receptors (BlpH) across 4,096 pneumococcal genomes. Imperfect concordance between nine QS signal peptide types and five phylogenetically-related QS receptor groups suggested extensive crosstalk between signals (where cells produce signals that non-clonal cells can detect) and eavesdropping (where cells respond to signals that they do not produce). To test these possibilities, we quantified the response of reporter strains containing each of six different blp QS receptor variants to cognate and non-cognate synthetic peptide signals. As predicted, we found evidence for crosstalk in five of six tested signals and for eavesdropping in four of these receptors. These in vitro results were confirmed during interactions between pneumococcal colonies grown adjacent to one another, providing direct evidence that crosstalk and eavesdropping occur at endogenous, ecologically-relevant, levels of signal secretion. Finally, using a spatially explicit stochastic model, we show that eavesdropping genotypes gain evolutionary advantages during inter-strain competition, even when their affinity to non-cognate signals is as low as 10% of the affinity to their cognate signal. Our results highlight the importance of social interactions in mediating intraspecific competition among bacteria and clarify that diverse competitive interactions can be mediated by polymorphism in QS systems.

https://www.biorxiv.org/content/early/2017/06/04/087247