Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Mol Microbiol. 2011 Dec;82(5):1277-90. doi: 10.1111/j.1365-2958.2011.07889.x. Epub 2011 Nov 4.
Productive intercellular delivery of cargo by secretory systems requires exquisite temporal and spatial choreography. Our laboratory has demonstrated that the haemolysin co-regulated secretion island I (HSI-I)-encoded type VI secretion system (H1-T6SS) of Pseudomonas aeruginosa transfers effector proteins to other bacterial cells. The activity of these effectors requires cell contact-dependent delivery by the secretion apparatus, and thus their export is highly repressed under planktonic growth conditions. Here we define regulatory pathways that orchestrate efficient secretion by this system. We identified a T6S-associated protein, TagF, as a posttranslational repressor of the H1-T6SS. Strains activated by TagF derepression or stimulated through a previously identified threonine phosphorylation pathway (TPP) share the property of secretory ATPase recruitment to the T6S apparatus, yet display different effector output levels and genetic requirements for their export. We also found that these two pathways respond to distinct stimuli; we identified surface growth as a physiological cue that activates the H1-T6SS exclusively through the TPP. Coordination of posttranslational triggering with cell contact-promoting growth conditions provides a mechanism for the T6SS to avoid wasteful release of effectors.
分泌系统通过细胞间的有效物质传递需要精确的时空协调。我们的实验室已经证明，铜绿假单胞菌的溶血素共调节分泌岛 I（HSI-I）编码的 VI 型分泌系统（H1-T6SS）将效应蛋白转移到其他细菌细胞中。这些效应物的活性需要通过分泌装置进行细胞接触依赖性传递，因此在浮游生长条件下，它们的输出受到高度抑制。在这里，我们定义了协调该系统有效分泌的调控途径。我们鉴定了一种 T6S 相关蛋白 TagF，它是 H1-T6SS 的一种翻译后抑制剂。通过 TagF 去抑制或通过先前鉴定的苏氨酸磷酸化途径（TPP）刺激而激活的菌株具有将分泌 ATP 酶募集到 T6S 装置的特性，但表现出不同的效应物输出水平和遗传要求。我们还发现这两种途径对不同的刺激有反应；我们发现表面生长是一种生理信号，它通过 TPP 专门激活 H1-T6SS。将翻译后触发与促进细胞接触的生长条件相协调，为 T6SS 提供了一种避免浪费释放效应物的机制。
