The Salmonella enterica PhoP directly activates the horizontally acquired SPI-2 gene sseL and is functionally different from a S. bongori ortholog.
The Salmonella enterica PhoP directly activates the horizontally acquired SPI-2 gene sseL and is functionally different from a S. bongori ortholog.
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DOI：
10.1371/journal.pone.0020024
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Finlay BB
中科院分区：
文献类型：
--
作者：
Gal-Mor O;Elhadad D;Deng W;Rahav G;Finlay BB
为了在宿主内建立成功的感染，病原体必须密切调节多种毒力性状以确保其准确的时空表达。作为一种高度适应的细胞内病原体，肠道沙门氏菌在其进化过程中通过许多侧向转移事件获得了各种毒力基因，包括获得沙门氏菌致病性岛2（SPI-2）及其相关效应物。水平获得的基因的有益使用要求它们的表达与细菌中已经存在的毒力程序和调节设置有效地协调。作为这种机制的一个例子，我们在这里表明，肠道沙门氏菌的祖先PhoPQ系统能够直接调节SPI-2效应基因sseL（编码分泌的去泛素化酶）在一个SsrB-独立的方式和PhoP在前馈调节回路，微调SseL的细胞水平的一部分。此外，我们证明了在sseL的启动子区域中存在保守的顺式调控元件，并显示纯化的PhoP与该区域的直接结合。有趣的是，与S. enterica PhoP是一个来自S.发现bongori SARC 12菌株在促进来自PhoP调节子的sseL和其它基因的转录方面受损。这些研究结果导致了一个以前未表征的残留物的DNA结合域的PhoP，这是所需的转录激活的PhoP调节基因在沙门氏菌属的鉴定。总的来说，我们的数据表明收购SSRB调节子和祖先的PhoPQ调控电路之间的一个有趣的接口，提供新的见解PhoP的功能，并强调水平收购的基因到肠道沙门氏菌的毒力网络的监管整合机制。
To establish a successful infection within the host, a pathogen must closely regulate multiple virulence traits to ensure their accurate temporal and spatial expression. As a highly adapted intracellular pathogen, Salmonella enterica has acquired during its evolution various virulence genes via numerous lateral transfer events, including the acquisition of the Salmonella Pathogenicity Island 2 (SPI-2) and its associated effectors. Beneficial use of horizontally acquired genes requires that their expression is effectively coordinated with the already existing virulence programs and the regulatory set-up in the bacterium. As an example for such a mechanism, we show here that the ancestral PhoPQ system of Salmonella enterica is able to regulate directly the SPI-2 effector gene sseL (encoding a secreted deubiquitinase) in an SsrB-independent manner and that PhoP plays a part in a feed-forward regulatory loop, which fine-tunes the cellular level of SseL. Additionally, we demonstrate the presence of conserved cis regulatory elements in the promoter region of sseL and show direct binding of purified PhoP to this region. Interestingly, in contrast to the S. enterica PhoP, an ortholog regulator from a S. bongori SARC 12 strain was found to be impaired in promoting transcription of sseL and other genes from the PhoP regulon. These findings have led to the identification of a previously uncharacterized residue in the DNA-binding domain of PhoP, which is required for the transcriptional activation of PhoP regulated genes in Salmonella spp. Collectively our data demonstrate an interesting interface between the acquired SsrB regulon and the ancestral PhoPQ regulatory circuit, provide novel insights into the function of PhoP, and highlight a mechanism of regulatory integration of horizontally acquired genes into the virulence network of Salmonella enterica.
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