The prpZ gene cluster encoding eukaryotic-type Ser/Thr protein kinases and phosphatases is repressed by oxidative stress and involved in Salmonella enterica serovar Typhi survival in human macrophages
The prpZ gene cluster encoding eukaryotic-type Ser/Thr protein kinases and phosphatases is repressed by oxidative stress and involved in Salmonella enterica serovar Typhi survival in human macrophages
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DOI：
10.1111/j.1574-6968.2008.01094.x
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发表时间：
2008-04-01
影响因子：
2.1
通讯作者：
Le Moual, Herve
中科院分区：
文献类型：
--
作者：
Faucher, Sebastien P.;Viau, Charles;Le Moual, Herve
prpZ基因簇由三个orf组成，编码与真核丝氨酸/苏氨酸蛋白磷酸酶2C （prpZ）和丝氨酸/苏氨酸蛋白激酶（prkY和prkX）同源的蛋白质。该簇存在于肠炎沙门氏菌血清型伤寒（S. Typhi）菌株Ty2和CT18的测序基因组中。本研究探讨了该基因簇的遗传组织、调控及其可能参与的毒力。逆转录酶(RT)-PCR证实，这三个基因转录为多顺反子mRNA。prpZ与lacZ的转录融合分析表明，prpZ位点在整个生长阶段都有表达。LacZ活性和实时RT-PCR显示，暴露于HOCl和过氧化氢后，mRNA的转录受到负调控。prpZ基因簇缺失突变体在感染后48小时在人巨噬细胞中的存活率明显低于亲本菌株Ty2。这些数据表明，prpZ、prkY和prkX是毒力基因，可能是控制伤寒沙门氏菌在宿主细胞中长期存活的信号通路的一部分。
The prpZ gene cluster consists of three ORFs coding for proteins with homology to eukaryotic-type Ser/Thr protein phosphatases 2C (prpZ) and Ser/Thr protein kinases (prkY and prkX). This cluster is present in the sequenced genomes of Salmonella enterica serovar Typhi (S. Typhi) strains Ty2 and CT18. This study investigated the genetic organization of this gene cluster, its regulation and its putative involvement in virulence. The three genes are transcribed as a polycistronic mRNA as demonstrated by reverse transcriptase (RT)-PCR. Analysis of a prpZ:lacZ transcriptional fusion showed that the prpZ locus is expressed throughout the growth phase. LacZ activity and real-time RT-PCR showed that transcription of the mRNA is negatively regulated upon exposure of cells to HOCl and, to a lesser extent, hydrogen peroxide. A deletion mutant of the prpZ gene cluster showed a significantly lower level of survival than the parental strain Ty2 in human macrophages at 48 h postinfection. Together these data suggest that prpZ, prkY and prkX are virulence genes that may be part of a signaling pathway controlling long-term survival of S. Typhi in host cells.