École Polytechnique Fédérale de Lausanne, Global Health Institute, Lausanne, Switzerland.
J Bacteriol. 2012 Feb;194(4):884-93. doi: 10.1128/JB.06417-11. Epub 2011 Dec 9.
ESAT-6 system 1 (ESX-1)-mediated secretion in Mycobacterium tuberculosis is dependent on proteins encoded by the cotranscribed espA-espC-espD gene cluster. While the roles of EspA and EspC with respect to the ESX-1 secretion system have been actively investigated, the function of EspD remains unknown. We show that EspD is secreted by M. tuberculosis, but unlike EspA and EsxA, its export does not exclusively require the ESX-1 system. Evidence for stabilization of cellular levels of EspA and EspC by EspD is presented, and depletion of EspD results in loss of EsxA secretion. Site-directed mutagenesis of EspD reveals that its role in the maintenance of cellular levels of EspA in M. tuberculosis is distinct from its facilitation of EsxA secretion. The same mutagenesis experiments have also shown that secretion of EspD is not required for the secretion of EsxA. Our findings highlight a critical and complex role for EspD in modulating the ESX-1 secretion system in M. tuberculosis.
结核分枝杆菌 ESAT-6 系统 1（ESX-1）介导的分泌依赖于与 espA-espC-espD 基因簇共转录的蛋白质。虽然 EspA 和 EspC 与 ESX-1 分泌系统的作用已被积极研究，但 EspD 的功能仍然未知。我们表明 EspD 由结核分枝杆菌分泌，但与 EspA 和 EsxA 不同，其输出不需要 ESX-1 系统。提出了 EspD 稳定 EspA 和 EspC 细胞水平的证据，并证明 EspD 的耗竭导致 EsxA 分泌丧失。EspD 的定点突变表明，其在维持结核分枝杆菌中 EspA 细胞水平中的作用与其促进 EsxA 分泌的作用不同。相同的诱变实验还表明，EspD 的分泌不是 EsxA 分泌所必需的。我们的研究结果突出了 EspD 在调节结核分枝杆菌 ESX-1 分泌系统中的关键而复杂的作用。
