The response regulator ComE in Streptococcus mutans functions both as a transcription activator of mutacin production and repressor of CSP biosynthesis

The response regulator ComE in Streptococcus mutans functions both as a transcription activator of mutacin production and repressor of CSP biosynthesis
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DOI:
10.1099/mic.0.2007/005975-0
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发表时间:
2007-06-01
期刊:
影响因子:
2.8
通讯作者:
Qi, Fengxia
Qi, Fengxia
中科院分区:
生物学4区
文献类型:
--
作者:
Kreth, Jens;Hung, David C. I.;Qi, Fengxia

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在肺炎链球菌中,能力基因和细菌素基因分别由ComED和BIpRH两个双组分系统控制。在变形链球菌中,这两种功能都由ComED系统控制。最近对变形链球菌的研究发现了一个潜在的ComE结合位点,其特征是响应能力刺激肽(CSP)的每个细菌素基因共享两个11 bp的直接重复序列。有趣的是,该序列并未出现在CSP结构基因comC的上游区域。由于comC被认为是csp响应和come依赖的自动调节回路的一部分,因此确定ComED系统如何可能同时调节细菌素表达和自然能力是很有兴趣的。利用csp应答菌素nlmC和comC共有的基因间区域IGS1499,研究人员证实,这两个基因都可能受到双功能ComE的调控。在comE零突变体中,comC基因表达与完全诱导的野生型相似。相比之下,nlmC基因表达几乎被消除。ComD的缺失对两个基因的影响与comE null突变相似。使用纯化的ComE进行的电泳迁移率转移试验(EMSAs)揭示了依赖于nlmC-comC启动子区域中一个或两个直接重复序列存在的特定转移模式。nlmC和comC的启动子活性也需要这两个直接重复序列。这些结果表明,变形链球菌的comC基因调控与报道的肺炎链球菌的comC基因调控有着根本的不同,这意味着一种独特的调控机制可以协调细菌素的产生和能力的发展。
In Streptococcus pneumoniae, competence and bacteriocin genes are controlled by two two-component systems, ComED and BIpRH, respectively. In Streptococcus mutans, both functions are controlled by the ComED system. Recent studies in S. mutans revealed a potential ComE binding site characterized by two 11 bp direct repeats shared by each of the bacteriocin genes responsive to the competence-stimulating peptide (CSP). Interestingly, this sequence was not found in the upstream region of the CSP structural gene comC. Since comC is suggested to be part of a CSP-responsive and ComE-dependent autoregulatory loop, it was of interest to determine how it was possible that the ComED system could simultaneously regulate bacteriocin expression and natural competence. Using the intergenic region IGS1499, shared by the CSP-responsive bacteriocin nlmC and comC, it was demonstrated that both genes are likely to be regulated by a bifunctional ComE. In a comE null mutant, comC gene expression was increased similarly to a fully induced wild-type. In contrast, nlmC gene expression was nearly abolished. Deletion of ComD exerted a similar effect on both genes to that observed with the comE null mutation. Electrophoretic mobility shift assays (EMSAs) with purified ComE revealed specific shift patterns dependent on the presence of one or both direct repeats in the nlmC-comC promoter region. The two direct repeats were also required for the promoter activity of both nlmC and comC. These results suggest that gene regulation of comC in S. mutans is fundamentally different from that reported for S. pneumoniae, which implicates a unique regulatory mechanism that allows the coordination of bacteriocin production with competence development.