Rietsch Arne, Vallet-Gely Isabelle, Dove Simon L, Mekalanos John J
Department of Microbiology and Molecular Genetics, Harvard Medical School, and Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2005 May 31;102(22):8006-11. doi: 10.1073/pnas.0503005102. Epub 2005 May 23.
Type III secretion systems are toxin delivery systems that are present in a large number of pathogens. A hallmark of all type III secretion systems studied to date is that expression of one or more of their components is induced upon cell contact. It has been proposed that this induction is controlled by a negative regulator that is itself secreted by means of the type III secretion machinery. Although candidate proteins for this negative regulator have been proposed in a number of systems, for the most part, a direct demonstration of their role in regulation is lacking. Here, we report the discovery of ExsE, a negative regulator of type III secretion gene expression in Pseudomonas aeruginosa. Deletion of exsE deregulates expression of the type III secretion genes. We provide evidence that ExsE is itself secreted by means of the type III secretion machinery and physically interacts with ExsC, a positive regulator of the type III secretion regulon. Taken together, these data demonstrate that ExsE is the secreted negative regulator that couples triggering of the type III secretion machinery to induction of the type III secretion genes.
III型分泌系统是存在于大量病原体中的毒素输送系统。迄今为止，所有已研究的III型分泌系统的一个标志是，其一种或多种组分的表达在细胞接触时被诱导。有人提出，这种诱导是由一种负调节因子控制的，该负调节因子本身通过III型分泌机制分泌。尽管在许多系统中都提出了这种负调节因子的候选蛋白，但在很大程度上，缺乏对它们在调节中作用的直接证明。在这里，我们报告了在铜绿假单胞菌中发现的ExsE，它是III型分泌基因表达的负调节因子。exsE的缺失会解除III型分泌基因表达的调控。我们提供的证据表明，ExsE本身通过III型分泌机制分泌，并与III型分泌调节子的正调节因子ExsC发生物理相互作用。综上所述，这些数据表明ExsE是一种分泌型负调节因子，它将III型分泌机制的触发与III型分泌基因的诱导联系起来。
