Interspecies communication among commensal and pathogenic streptococci.
Interspecies communication among commensal and pathogenic streptococci.
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DOI：
10.1128/mbio.00382-13
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发表时间：
2013-07-23
期刊：
影响因子：
6.4
通讯作者：
Federle MJ
中科院分区：
文献类型：
--
作者：
Cook LC;LaSarre B;Federle MJ
群体感应（Quorum sensing，QS）调节细菌的多种协调行为，包括毒力因子的产生、生物膜形成、孢子形成和感受态发育。现在已经确定，一些链球菌利用Rgg型蛋白与短疏水肽（SHP）一起介导QS，序列分析表明，几种链球菌含有高度同源的Rgg/SHP对。在A组链球菌（GAS）中，先前确定两种SHP（SHP 2和SHP 3 [SHP 2/3]）在GAS生物膜形成中起重要作用。SHP 2/3由两种拮抗调节剂Rgg 2和Rgg 3检测，其控制shp基因的表达。在B组链球菌（GBS）中，RovS是已知的毒力基因调节子和Rgg 2的直系同源物，而不存在明显的Rgg 3同源物。与rovS相邻的是编码与SHP 2几乎相同的肽的基因（shp 1520）。使用同基因突变株和转录报告基因，我们证实了RovS/SHP 1520在GBS中包含QS回路。更重要的是，我们进行了实验，证明GBS产生和分泌SHP 1520可以调节GAS中Rgg 2/3调控的基因表达;同样，GAS产生SHP 2/3可以刺激GBS中RovS介导的基因调控。停乳链球菌（Streptococcus dysgalactiae subsp.）equisimilis也产生能够模拟GAS和GBS的QS回路的分泌因子，并且测序证实了在该物种中也存在正向同源Rgg 2/SHP 2对。据我们所知，这是第一个记录在案的情况下，链球菌物种之间的双向信号在共培养，并建议orthobacterium Rgg/SHP系统的重要人类病原体之间的种间通信的作用。致病性链球菌，如A组（GAS）和B组（GBS）链球菌，能够在人体内持续存在而不引起疾病，但在某些尚未完全表征的条件下变得致病。人类植物群成员之间的环境信号和种间信号可能在疾病状态的转变中发挥重要作用。由于群体感应（QS）肽已被一致地显示为调节致病物种中的毒力因子产生，细菌通过这些肽发出信号的能力可能被证明是载体和致病状态之间的重要联系。在这里，我们提供了一个双向QS系统之间的GAS，GBS，停乳链球菌亚种的证据。equisimilis，证明了人类病原体之间进化通信系统的可能性。
Quorum sensing (QS) regulates diverse and coordinated behaviors in bacteria, including the production of virulence factors, biofilm formation, sporulation, and competence development. It is now established that some streptococci utilize Rgg-type proteins in concert with short hydrophobic peptides (SHPs) to mediate QS, and sequence analysis reveals that several streptococcal species contain highly homologous Rgg/SHP pairs. In group A streptococcus (GAS), two SHPs (SHP2 and SHP3 [SHP2/3]) were previously identified to be important in GAS biofilm formation. SHP2/3 are detected by two antagonistic regulators, Rgg2 and Rgg3, which control expression of the shp genes. In group B streptococcus (GBS), RovS is a known virulence gene regulator and ortholog of Rgg2, whereas no apparent Rgg3 homolog exists. Adjacent to rovS is a gene (shp1520) encoding a peptide nearly identical to SHP2. Using isogenic mutant strains and transcriptional reporters, we confirmed that RovS/SHP1520 comprise a QS circuit in GBS. More important, we performed experiments demonstrating that production and secretion of SHP1520 by GBS can modulate Rgg2/3-regulated gene expression in GAS in trans; likewise, SHP2/3 production by GAS can stimulate RovS-mediated gene regulation in GBS. An isolate of Streptococcus dysgalactiae subsp. equisimilis also produced a secreted factor capable of simulating the QS circuits of both GAS and GBS, and sequencing confirms the presence of an orthologous Rgg2/SHP2 pair in this species as well. To our knowledge, this is the first documented case of bidirectional signaling between streptococcal species in coculture and suggests a role for orthologous Rgg/SHP systems in interspecies communication between important human pathogens. Pathogenic streptococci, such as group A (GAS) and group B (GBS) streptococcus, are able to persist in the human body without causing disease but become pathogenic under certain conditions that are not fully characterized. Environmental cues and interspecies signaling between members of the human flora likely play an important role in the transition to a disease state. Since quorum-sensing (QS) peptides have been consistently shown to regulate virulence factor production in pathogenic species, the ability of bacteria to signal via these peptides may prove to be an important link between the carrier and pathogenic states. Here we provide evidence of a bidirectional QS system between GAS, GBS, and Streptococcus dysgalactiae subsp. equisimilis, demonstrating the possibility of evolved communication systems between human pathogens.