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 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.
Faucher
Sébastien P
SP
Department of Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada.
Viau
Charles
C
Gros
Pierre-Paul
PP
Daigle
France
F
Le Moual
Hervé
H
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology*; D005810:Multigene Family; D018384:Oxidative Stress; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012485:Salmonella typhi / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D017384:Sequence Deletion; D014158:Transcription, Genetic / Q000187:drug effects; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D037521:Virulence Factors; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases