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
FEMS MICROBIOLOGY LETTERS
Authors: Faucher, Sebastien P.; Viau, Charles; Gros, Pierre-Paul; Daigle, France; Le Moual, Herve
Abstract
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.
Screening hub genes in coronary artery disease based on integrated analysis
CARDIOLOGY JOURNAL
Authors: Long, Fei; Wang, Ling; Yang, Lei; Ji, Zhou; Hu, YaGuang
Abstract
Background: Coronary artery disease (CAD) is the leading cause of mortality worldwide. Identifying key pathogenic genes benefits the understanding molecular mechanism of CAD. Methods: In this study, 5 microarray data sets from the blood sample of 312 CADS and 277 healthy controls were downloaded. Limma and metaMA packages were used to identify differentially expressed genes. The functional enrichment analysis of differentially expressed genes was further performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Additionally, protein-protein interaction and transcript factors-target networks were performed based on top 10 up- and down-regulated differentially expressed genes to further study the biological function. Last, real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate the integrated analysis result. Results: A total of 528 differentially expressed genes were obtained. All differentially expressed genes were significantly involved in signal transduction and the MAPK signaling pathway. Among MAPK signaling pathway, IL1R2, ARRB2 and PRKX were associated with CAD. Furthermore, there were 4 common differentially expressed genes including PLAUR HSPH1, ZMYND11 and S100A8 in the protein-protein interaction and transcript factors-target networks, which played crucial roles in the development of CAD. In quantitative RT-qPCR, the expression of PRKX, HSPH1 and ZMYND11 was down-regulated and consistent with the integrated analysis. Conclusions: Identified 7 differentially expressed genes (IL1R2, ARRB2, PRKX, PLAUR, HSPH1, ZMYND11 and S100A8) may play crucial roles in the development of CAD.