Interplay between Rho, H-NS, spurious transcription, and Salmonella gene regulation.
Interplay between Rho, H-NS, spurious transcription, and Salmonella gene regulation.
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DOI：
10.1073/pnas.2211222119
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发表时间：
2022-08-16
影响因子：
11.1
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中科院分区：
文献类型：
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沙门氏菌致病岛1(SPI-1)编码的III型分泌系统(T3SS)是沙门氏菌的主要毒力因子，是引发炎症性腹泻所必需的，炎症性腹泻是沙门氏菌病的标志，并侵袭肠道上皮，导致潜在的致命性全身感染。SPI-1 T3SS的表达受复杂的调控电路控制。表达的一个重要方面是它是双峰的；在大多数情况下，只有一部分细胞诱导SPI-1系统。在PNA中，Figueroa-Bossi等人(1)发现了转录终止子Rho、异源沉默因子H-NS(组蛋白样核结构蛋白)和SPI-1调节因子Hild之间有趣的功能相互作用，这有助于双峰SPI-1表达的转变。这项工作揭示了Rho介导的转录终止和虚假转录(或转录噪声)在调控中的更深层次作用。35千碱基的SPI-1“岛”是水平获得性毒力基因座的典型例子。事实上，它的收购，大约140 Mya，创造了沙门氏菌物种(2)。该基因具有致病岛的特点，其鸟嘌呤-胞嘧啶(GC)含量(45%)低于祖先染色体(52%)。SPI-1的转录也是典型的水平获得的DNA，通常被类核相关蛋白H-NS沉默，H-NS与富含腺嘌呤胸腺嘧啶(AT)的成核部位结合，并在DNA上聚合或相互作用并桥接结合部位(3，4)。因此，H-NS阻断了转录激活剂和/或RNA聚合酶的结合。致病岛之所以富含AT，正是因为它们可以被H-NS沉默。水平获得的富含GC的DNA可能会以一种不受调控的方式表达，并被挑选出来。一旦获得H-NS并使其沉默，细菌就可以进化出适当调节孤岛基因的机制，使细胞受益。SPI-1的表达受到三个类似AraC的调节器的调节，即Hild、HilC和RTSA，它们在一个复杂的前馈环中激活Hila的表达，编码T3SS结构基因的转录激活因子(5)。该系统已经进化到对环境和细胞的生理状态高度敏感，对许多全球调节系统做出反应。绝大多数调控信号是通过HILD整合的，其表达和活性在多个水平上受到控制：转录启动、信使RNA(MRNA)翻译、mRNA稳定性和HILD蛋白活性(6)。在蛋白质水平上，hILE直接与hILD结合以阻止DNA结合。HILE产生的水平相对较低，是设定诱导该系统所需的HILD活动阈值的因素之一(7)。HILC和RTSA充当任何诱导信号的放大器。一个简单的模型表明，H-NS覆盖整个SPI-1基因座，转录激活子主要起作用
The type III secretion system (T3SS) encoded in the Salmonella pathogenicity island 1 (SPI-1) is a primary virulence factor for Salmonella, required for initiating the inflammatory diarrhea that is the hallmark of salmonellosis and for invading the intestinal epithelium, leading to potentially lethal systemic infection. Expression of the SPI-1 T3SS is controlled by a complex regulatory circuit. One important aspect of expression is that it is bimodal; under most conditions, only a subset of cells induces the SPI-1 system. In PNAS, Figueroa-Bossi et al.(1) have uncovered an interesting functional interaction among the transcription terminator Rho, the xenogenic silencer H-NS (histone-like nucleoid-structuring protein), and the SPI-1 regulator HilD that contributes to a shift in bimodal SPI-1 expression. This work reveals a deeper role for Rho-mediated transcriptional termination and spurious transcription (or transcriptional noise) in regulation. The 35-kilobase SPI-1 “island” is a classic example of a horizontally acquired virulence locus. Indeed, its acquisition, some 140 Mya, created the Salmonella species (2). Characteristic of pathogenicity islands, the locus has a low Guanine-Cytosine (GC) content (45%) relative to the ancestral chromosome (52% GC). Also typical of horizontally acquired DNA, transcription of SPI-1 is generally silenced by the nucleoid-associated protein, H-NS, which binds to Adenine-Thymine (AT)-rich nucleation sites and polymerizes on DNA or interacts and bridges binding sites (3, 4). Thus, H-NS blocks binding of transcriptional activators and/or RNA polymerase. Pathogenicity islands are AT rich precisely because they could be silenced by H-NS. Horizontally acquired GC-rich DNA would presumably be expressed in an unregulated fashion and be selected against. Once acquired and silenced by H-NS, the bacterium can evolve mechanisms to appropriately regulate the island genes to the benefit of the cell.SPI-1 expression is regulated by three AraC-like regulators, HilD, HilC, and RtsA, which act in a complex feedforward loop to activate expression of hilA, encoding the transcriptional activator of the T3SS structural genes (5). The system has evolved to be highly sensitive to the environment and physiological status of the cell, responding to a number of global regulatory systems. The vast majority of regulatory signals are integrated through HilD, whose expression and activity are controlled at multiple levels: transcription initiation, messenger RNA (mRNA) translation, mRNA stability, and HilD protein activity (6). At the protein level, HilE directly binds to HilD to prevent DNA binding. HilE is produced at a relatively low level and acts as one of the factors setting the threshold for HilD activity required to induce the system (7). HilC and RtsA act as amplifiers of any inducing signals. A simple model would suggest that H-NS coats the entire SPI-1 locus and that the transcriptional activators act primarily
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影响因子：
6.4
作者：
Desai PT;Porwollik S;Long F;Cheng P;Wollam A;Bhonagiri-Palsikar V;Hallsworth-Pepin K;Clifton SW;Weinstock GM;McClelland M
通讯作者：
McClelland M
影响因子：
3.2
作者：
Grenz, Jesse R.;Chubiz, Jessica E. Cott;Slauch, James M.
通讯作者：
Slauch, James M.
影响因子：
4.5
作者：
Bossi, Lionello;Ratel, Mathilde;Figueroa-Bossi, Nara
通讯作者：
Figueroa-Bossi, Nara
影响因子：
3.7
作者：
Teixidó L;Carrasco B;Alonso JC;Barbé J;Campoy S
通讯作者：
Campoy S
影响因子：
3.2
作者：
Kalafatis, Marinos;Slauch, James M.
通讯作者：
Slauch, James M.