Expression and secretion of Salmonella pathogenicity island-2 virulence genes in response to acidification exhibit differential requirements of a functional type III secretion apparatus and SsaL
Expression and secretion of Salmonella pathogenicity island-2 virulence genes in response to acidification exhibit differential requirements of a functional type III secretion apparatus and SsaL
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DOI：
10.1074/jbc.m404299200
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发表时间：
2004-11-26
影响因子：
4.8
通讯作者：
Finlay, BB
中科院分区：
文献类型：
--
作者：
Coombes, BK;Brown, NF;Finlay, BB
沙门氏菌致病岛 (SPI)-2 对于沙门氏菌的细胞内存活和哺乳动物的毒力至关重要。 SPI-2 编码易位到宿主细胞中的毒力因子（称为效应子）、III 型分泌装置和调节 SPI-2 细胞内表达的两部分调节系统。沙门氏菌 SPI-2 分泌活性似乎是对其复制的液泡酸化作出反应而诱导的。在这里，我们表明，SPI-2蛋白、SseB和SseD（分别是分泌装置的丝状和孔形成成分）响应酸化的表达需要完整的分泌系统和SsaL，SsaL是SepL的沙门氏菌同源物，SsaL是III型依赖性易位蛋白分泌所需的调节剂，但不是附着和消除胃肠道病原体的效应子。我们表明，SPI-2 编码效应子的表达受酸调节，但可以与丝和易位子成分的表达解偶联，从而显示 SsaL 对表达的不同要求。 SPI-2编码效应子的分泌和易位需要SsaL，但SsaL对于其他致病位点编码的SPI-2效应子的分泌来说是可有可无的，这表明SsaL具有分泌调节功能。此外，我们证明 sseA 操纵子（sseD 和 sseE）内相邻基因的差异表达发生在转录水平。这些数据表明沙门氏菌 SPI-2 激活状态是通过需要 SsaL 的酸调节反应来实现的。这些数据还表明，SPI-2 内存在 sseD 下游“效应操纵子”区域的先前未被识别的调控元件，该区域可能区分易位子和效应子的表达。
Salmonella pathogenicity island (SPI)-2 is pivotal to the intracellular survival of Salmonella and for virulence in mammals. SPI-2 encodes virulence factors (called effectors) that are translocated into the host cell, a type III secretion apparatus and a two-component regulatory system that regulates intracellular expression of SPI-2. Salmonella SPI-2 secretion activity appears to be induced in response to acidification of the vacuole in which it replicates. Here we show that the expression of the SPI-2 proteins, SseB and SseD (filament and pore forming components of the secretion apparatus, respectively) in response to acidification requires an intact secretion system and SsaL, a Salmonella homologue of SepL, a regulator required for type III-dependent secretion of translocators but not effectors in attaching and effacing gastrointestinal pathogens. We show that the expression of SPI-2-encoded effectors is acid-regulated but can be uncoupled from the expression of filament and translocon components, thus showing a differential requirement of SsaL for expression. The secretion and translocation of SPI-2-encoded effectors requires SsaL, but SsaL is dispensable for the secretion of SPI-2 effectors encoded in other pathogenicity loci, suggesting a secretion regulation function for SsaL. Further, we demonstrate that the differential expression of adjacent genes within the sseA operon (sseD and sseE) occurs at the transcriptional level. These data indicate that a Salmonella SPI-2 activation state is achieved by an acid-regulated response that requires SsaL. These data also suggest the existence of a previously unrecognized regulatory element within SPI-2 for the "effector operon" region downstream of sseD that might demarcate the expression of translocators and effectors.