Peptide-assisted degradation of the Salmonella MgtC virulence factor
Peptide-assisted degradation of the Salmonella MgtC virulence factor
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DOI：
10.1038/sj.emboj.7601983
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发表时间：
2008-02-06
期刊：
影响因子：
11.4
通讯作者：
Blanc-Potard, Anne-Beatrice
中科院分区：
文献类型：
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作者：
Alix, Eric;Blanc-Potard, Anne-Beatrice
MgtC 是几种细胞内病原体共有的毒力因子，是巨噬细胞在缺镁培养基中生存和生长所必需的。在肠沙门氏菌中，MgtC 与 MgtB 镁转运蛋白共表达，并且 mgtCB 操纵子的转录由镁剥夺诱导。尽管在镁耗尽的培养基中 mgtCB 转录诱导水平很高，但在野生型沙门氏菌菌株中几乎检测不到 MgtC 蛋白。在这里，我们表明 MgtC 表达的下调依赖于由 mgtCB 操纵子编码的疏水肽 MgtR。我们的结果表明，MgtR 促进 FtsH 蛋白酶对 MgtC 的降解，从而提供负调节反馈。细菌双杂交测定表明 MgtR 与内膜 MgtC 蛋白相互作用。我们鉴定了 MgtR 和 MgtC 的突变衍生物，它们阻止了两个伙伴之间的调节和相互作用。在巨噬细胞中，MgtR 肽的过度表达导致沙门氏菌复制率降低。这项研究强调了肽在细菌调节机制中的作用，并提供了 MgtC 毒力因子的天然拮抗剂。
MgtC is a virulence factor common to several intracellular pathogens that is required for intramacrophage survival and growth in magnesium-depleted medium. In Salmonella enterica, MgtC is coexpressed with the MgtB magnesium transporter and transcription of the mgtCB operon is induced by magnesium deprivation. Despite the high level of mgtCB transcriptional induction in magnesium-depleted medium, the MgtC protein is hardly detected in a wildtype Salmonella strain. Here, we show that downregulation of MgtC expression is dependent on a hydrophobic peptide, MgtR, which is encoded by the mgtCB operon. Our results suggest that MgtR promotes MgtC degradation by the FtsH protease, providing a negative regulatory feedback. Bacterial two-hybrid assays demonstrate that MgtR interacts with the inner-membrane MgtC protein. We identified mutant derivatives of MgtR and MgtC that prevent both regulation and interaction between the two partners. In macrophages, overexpression of the MgtR peptide led to a decrease of the replication rate of Salmonella. This study highlights the role of peptides in bacterial regulatory mechanisms and provides a natural antagonist of the MgtC virulence factor.