The Staphylococcus aureus Protein-Coding Gene gdpS Modulates sarS Expression via mRNA-mRNA Interaction
The Staphylococcus aureus Protein-Coding Gene gdpS Modulates sarS Expression via mRNA-mRNA Interaction
复制标题
金黄色葡萄球菌蛋白编码基因 gdpS 通过 mRNA-mRNA 相互作用调节 sarS 表达
DOI：
10.1128/iai.00159-15
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发表时间：
2015-08-01
影响因子：
3.1
通讯作者：
Xue, Ting
中科院分区：
文献类型：
--
作者：
Chen, Chuan;Zhang, Xu;Xue, Ting
摘要金黄色葡萄球菌是一种重要的革兰氏阳性病原体，可引起从局部皮肤感染到危及生命的全身性感染等多种疾病。对S.金黄色葡萄球菌的致病性基本上由多种因素决定，包括细胞壁相关蛋白和分泌的毒素，它们响应于环境变化而被精确控制。葡萄球菌GGDEF结构域蛋白（GdpS）是葡萄球菌中唯一不参与c-di-GMP合成但参与S. aureus NCTC 8325.我们以前的研究表明，gdpS的失活产生了广泛的变化，毒力因子一起，特别是一个主要的SPA（蛋白A）表面蛋白。据报道，sarS是SPA的直接正调节剂。与亲本NCTC 8325菌株相比，gdpS突变体中sarS的转录水平降低，表明gdpS通过与sarS相互作用影响spa。本研究通过定点突变和互补实验证明gdpS的翻译产物不参与sarS转录水平的调控。我们发现gdpS通过与sarS mRNA的5′非翻译区（5′UTR）的RNA-RNA碱基直接配对发挥作用，推测的18个核苷酸的区域在调控过程中起重要作用。此外，在gdpS突变体中sarS的mRNA半衰期分析表明，gdpS通过促进sarS mRNA的稳定性来正向调节sarS的mRNA水平，这表明gdpS mRNA可能以RNA依赖的途径调节spa的表达。
ABSTRACT Staphylococcus aureus is an important Gram-positive pathogen responsible for numerous diseases ranging from localized skin infections to life-threatening systemic infections. The virulence of S. aureus is essentially determined by a wide spectrum of factors, including cell wall-associated proteins and secreted toxins that are precisely controlled in response to environmental changes. GGDEF domain protein from Staphylococcus (GdpS) is the only conserved staphylococcal GGDEF domain protein that is involved not in c-di-GMP synthesis but in the virulence regulation of S. aureus NCTC8325. Our previous study showed that the inactivation of gdpS generates an extensive change of virulence factors together with, in particular, a major Spa (protein A) surface protein. As reported, sarS is a direct positive regulator of spa. The decreased transcript levels of sarS in the gdpS mutant compared with the parental NCTC8325 strain suggest that gdpS affects spa through interaction with sarS. In this study, site mutation and complementary experiments showed that the translation product of gdpS was not involved in the regulation of transcript levels of sarS. We found that gdpS functioned through direct RNA-RNA base pairing with the 5′ untranslated region (5′UTR) of sarS mRNA and that a putative 18-nucleotide region played a significant role in the regulatory process. Furthermore, the mRNA half-life analysis of sarS in the gdpS mutant showed that gdpS positively regulates the mRNA levels of sarS by contributing to the stabilization of sarS mRNA, suggesting that gdpS mRNA may regulate spa expression in an RNA-dependent pathway.