Regulation of type III secretion in Bordetella
Regulation of type III secretion in Bordetella
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DOI：
10.1111/j.1365-2958.2004.04053.x
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发表时间：
2004-05-01
影响因子：
3.6
通讯作者：
Miller, JF
中科院分区：
文献类型：
--
作者：
Mattoo, S;Yuk, MH;Miller, JF
BvgAS毒力控制系统调节感染人类和其他哺乳动物的波尔德氏菌亚种中III型分泌基因的表达。我们已经确定了五个开放阅读框架，BTRs，btrU，btrX，btrW和btrV，它们由BvgAS激活，编码调节因子，在转录、蛋白表达和分泌水平控制III型分泌。BTRS基因产物与ECF(胞浆外功能)Sigma因子具有序列相似性，是转录BSc基因座所必需的。BtrU、btrW和btrV编码的蛋白分别含有PP2C样丝氨酸磷酸酶、HPK(组蛋白激酶)样丝氨酸蛋白激酶和STAS抗Sigma因子拮抗剂结构域，这些都是枯草芽孢杆菌革兰氏阳性伙伴转换蛋白的特征。BtrU和BtrW是分泌BSCIII型分泌系统输出的蛋白质所必需的，而BtrV是蛋白质合成和/或稳定性所必需的。因此，波氏杆菌物种进化出了一种独特的级联反应，以差异调节III型分泌，该级联反应结合了一个带有ECF sigma因子的典型磷酸传递系统和一组具有定义伙伴开关的结构域签名的蛋白质，这些蛋白质传统上被认为只在革兰氏阳性细菌中起作用。多层调控机制的存在很可能反映了在控制III型分泌时整合多种信号的需要。Bsc和btr基因座在广泛寄主范围内的波氏杆菌和人类特有的波尔德氏菌之间几乎相同。对波尔德氏菌亚种的比较分析表明，Bsc和Btr基因座在所有亚种中都有转录，但只有广泛寄主范围的菌株在体外表达了III型分泌系统。在人类适应的菌株中，III型分泌的阻断是转录后的，信号识别似乎是不同亚种之间的一个分歧点。
The BvgAS virulence control system regulates the expression of type III secretion genes in Bordetella subspecies that infect humans and other mammals. We have identified five open reading frames, btrS, btrU, btrX, btrW and btrV, that are activated by BvgAS and encode regulatory factors that control type III secretion at the levels of transcription, protein expression and secretion. The btrS gene product bears sequence similarity to ECF (extracytoplasmic function) sigma factors and is required for transcription of the bsc locus. btrU, btrW and btrV encode proteins predicted to contain PP2C-like Ser phosphatase, HPK (His protein kinase)-like Ser kinase and STAS anti-sigma factor antagonist domains, respectively, which are characteristic of Gram-positive partner switching proteins in Bacillus subtilis. BtrU and BtrW are required for secretion of proteins that are exported by the bsc type III secretion system, whereas BtrV is specifically required for protein synthesis and/or stability. Bordetella species have thus evolved a unique cascade to differentially regulate type III secretion that combines a canonical phosphorelay system with an ECF sigma factor and a set of proteins with domain signatures that define partner switchers, which were traditionally thought to function only in Gram-positive bacteria. The presence of multiple layers and mechanisms of regulation most likely reflects the need to integrate multiple signals in controlling type III secretion. The bsc and btr loci are nearly identical between broad-host-range and human-specific Bordetella. Comparative analysis of Bordetella subspecies revealed that, whereas bsc and btr loci were transcribed in all subspecies, only broad-host-range strains expressed a functional type III secretion system in vitro. The block in type III secretion is post-transcriptional in human-adapted strains, and signal recognition appears to be a point of divergence between subspecies.