A yeast-based genetic screen for identification of pathogenic Salmonella proteins
A yeast-based genetic screen for identification of pathogenic Salmonella proteins
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DOI：
10.1111/j.1574-6968.2009.01630.x
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发表时间：
2009-07-01
影响因子：
2.1
通讯作者：
Molina, Maria
中科院分区：
文献类型：
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作者：
Aleman, Ainel;Fernandez-Pinar, Pablo;Molina, Maria
沙门氏菌使用III型分泌系统（TTSS）将致病蛋白质递送到宿主细胞中。这些易位的效应子通过靶向真核生物中保守的重要细胞过程诱导细菌内化和细胞内增殖。在这里，我们评估了在酵母中进行遗传筛选的可行性，以确定新的沙门氏菌效应，通过寻找在该模型系统中表达时产生毒性的基因。我们确定了几个已知的TTSS易位效应，并发现其中两个，SteC和SseF，从沙门氏菌肠血清型鼠伤寒，干扰细胞骨架动力学，因为它们在哺乳动物细胞。我们还鉴定了11个功能未知的基因（7个来自S.伤寒沙门氏菌4株; Typhimurium），其显示效应蛋白通常显示的特征，例如（G+C）含量低于染色体的平均值，表明它们通过水平转移过程获得。这些蛋白质中的五个仅在沙门氏菌血清型中高度保守，而其他六个在其他致病性或机会性肠杆菌中也是保守的。此外，我们还发现了与已知参与发病机制的易位蛋白或细菌限制蛋白共享特定活性结构域的其他蛋白质，这些蛋白质也可能作为毒力蛋白。
Salmonella uses type III secretion systems (TTSS) to deliver pathogenic proteins into the host cells. These translocated effectors induce bacterial internalization and intracellular proliferation by targeting important cellular processes that are conserved among eukaryotes. Here, we assessed the feasibility of performing a genetic screen in yeast to identify novel Salmonella effectors, by searching for genes that produce toxicity when expressed in this model system. We identified several known TTSS-translocated effectors and found that two of them, SteC and SseF, from Salmonella enterica serovar Typhimurium, interfere with cytoskeletal dynamics as they do in mammalian cells. We also identified 11 genes of unknown function (seven from S. Typhi and four from S. Typhimurium) that display features commonly showed by effector proteins, such as a (G+C) content lower than the average for the chromosome, suggesting their acquisition by horizontal transfer processes. Five of these proteins are highly conserved only among Salmonella serovars, whereas the other six are also conserved in other pathogenic or opportunistic enterobacteria. Moreover, we identified other proteins that share specific activity domains with either translocated or bacterial-confined proteins known to be involved in pathogenesis, which might also act as virulence proteins.