Rang Cécile, Alix Eric, Felix Christine, Heitz Annie, Tasse Lena, Blanc-Potard Anne-Béatrice
INSERM U431, Avenir Team, Faculté de Médecine, Avenue J. F. Kennedy, 30908 Nîmes Cedex 02, France.
Mol Microbiol. 2007 Jan;63(2):605-22. doi: 10.1111/j.1365-2958.2006.05542.x. Epub 2006 Dec 14.
MgtC is required for intramacrophage replication of intracellular pathogens and growth in low Mg(2+) medium. A link between these two phenotypes has been proposed due to putative Mg(2+) deprivation inside phagosome. MgtC is part of a family of proteins that share a conserved N-terminal transmembrane domain and a variable C-terminal domain. A combination of predictive and experimental approaches indicates that the Salmonella MgtC C-terminal domain is cytoplasmic, adopts a fold also found in metal transporters and RNA interacting domain, and does not bind Mg(2+). MgtC homologues from diverse gamma-proteobacteria, including the extracellular pathogens Yersinia pestis, Photorhabdus luminescens and Pseudomonas aeruginosa, have been expressed in a SalmonellaDeltamgtC strain. The Y. pestis MgtC fully replaced the Salmonella MgtC whereas P. luminescens or P. aeruginosa MgtC complemented only in low Mg(2+) medium, thus dissociating for the first time the two MgtC-related phenotypes. In addition, we identified single amino acids changes that prevent or promote MgtC role in macrophages without affecting MgtC role in low Mg(2+) culture. A SalmonellaDeltamgtC strain showed elongated and autoaggregated bacteria in low Mg(2+) medium but not in macrophages. Taken together our results suggest that MgtC has a dual role when bacteria localize in macrophages or low Mg(2+) environment.
MgtC是细胞内病原体在巨噬细胞内复制以及在低镁（Mg²⁺）培养基中生长所必需的。由于吞噬体内可能存在镁离子剥夺现象，有人提出了这两种表型之间的联系。MgtC是一类蛋白质家族的成员，该家族共享一个保守的N端跨膜结构域和一个可变的C端结构域。预测性和实验性方法相结合表明，沙门氏菌MgtC的C端结构域位于细胞质中，具有在金属转运蛋白和RNA相互作用结构域中也能找到的折叠结构，并且不结合镁离子（Mg²⁺）。来自不同γ-变形菌的MgtC同源物，包括细胞外病原体鼠疫耶尔森菌、发光光杆状菌和铜绿假单胞菌，已在沙门氏菌ΔmgtC菌株中表达。鼠疫耶尔森菌的MgtC完全替代了沙门氏菌的MgtC，而发光光杆状菌或铜绿假单胞菌的MgtC仅在低镁（Mg²⁺）培养基中发挥互补作用，从而首次将与MgtC相关的两种表型分离开来。此外，我们鉴定出了一些单氨基酸变化，这些变化可阻止或促进MgtC在巨噬细胞中的作用，而不影响其在低镁（Mg²⁺）培养中的作用。沙门氏菌ΔmgtC菌株在低镁（Mg²⁺）培养基中显示出细菌伸长和自动聚集的现象，但在巨噬细胞中则没有。综合我们的研究结果表明，当细菌定位于巨噬细胞或低镁（Mg²⁺）环境中时，MgtC具有双重作用。
