The intracellular pathogen Legionella pneumophila translocates more than 300 effector proteins into its host cells. The expression levels of the genes encoding these effectors are orchestrated by an intricate regulatory network. Here, we introduce LelA, the first L. pneumophila LysR-type transcriptional regulator of effectors. Through bioinformatic and experimental analyses, we identified the LelA target regulatory element and demonstrated that it directly activates the expression of three L. pneumophila effectors (legL7, legL6, and legU1). We further found that the gene encoding LelA is positively regulated by the RpoS sigma factor, thus linking it to the known effector regulatory network. Examination of other species throughout the Legionella genus revealed that this regulatory element is found upstream of 34 genes encoding validated effectors, putative effectors, and hypothetical proteins. Moreover, ten of these genes were examined and found to be activated by the L. pneumophila LelA as well as by their orthologs in the corresponding species. LelA represents a novel type of Legionella effector regulator, which coordinates the expression of both adjacently and distantly located effector-encoding genes, thus forming small groups of co-regulated effectors.

中文翻译：

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LysR 型转录调节因子 LelA 共同调节不同军团菌中的各种效应子

细胞内病原体嗜肺军团菌将 300 多种效应蛋白易位到其宿主细胞中。编码这些效应子的基因的表达水平是由复杂的调控网络精心安排的。在这里，我们介绍了 LelA，第一个嗜肺军团菌LysR 型效应子转录调节因子。通过生物信息学和实验分析，我们确定了 LelA 靶标调控元件，并证明它直接激活三个嗜肺军团菌效应子（legL7、legL6和legU1 ）的表达。我们进一步发现编码LelA的基因受到RpoS sigma因子的正向调节，从而将其与已知的效应调节网络联系起来。对整个军团菌属其他物种的检查表明，这种调节元件存在于编码已验证效应子、推定效应子和假设蛋白质的 34 个基因的上游。此外，对这些基因中的十个进行了检查，发现它们被嗜肺军团菌LelA 及其相应物种的直系同源物激活。 LelA代表了一种新型的军团菌效应调节因子，它协调邻近和远处效应编码基因的表达，从而形成共同调节的效应子小群。