title: The iron-sensing fur regulator controls expression timing and levels of salmonella pathogenicity island 2 genes in the course of environmental acidification.
abstract: In order to survive inside macrophages, Salmonella produces a series of proteins encoded by genes within Salmonella pathogenicity island 2 (SPI-2). In the present study, we report that Fur, a central regulator of iron utilization, negatively controls the expression of SPI-2 genes. Time course analysis of SPI-2 expression after the entry of Salmonella into macrophages revealed that SPI-2 genes are induced earlier and at higher levels in the absence of the Fur regulator. It was hypothesized that Fur repressed the SPI-2 expression that was activated during acidification of the phagosome. Indeed, as pH was lowered from pH 7.0 to pH 5.5, the lack of Fur enabled SPI-2 gene expression to be induced at higher pH and to be expressed at higher levels. Fur controlled SPI-2 genes via repression of the SsrB response regulator, a primary activator of SPI-2 expression. Fur repressed ssrB expression both inside macrophages and under acidic conditions, which we ascribe to the direct binding of Fur to the ssrB promoter. Our study suggests that Salmonella could employ iron inside the phagosome to precisely control the timing and levels of SPI-2 expression inside macrophages.
authors.affiliation: Division of Microbiology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, South Korea.
authors.forename: Eunna
authors.initials: E
authors.lastname: Choi
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Kim
authors.forename: Hwiseop
authors.initials: H
authors.lastname: Lee
authors.forename: Daesil
authors.initials: D
authors.lastname: Nam
authors.forename: Jeongjoon
authors.initials: J
authors.lastname: Choi
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Shin
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism* / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D044404:Genomic Islands / Q000235:genetics / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000502:physiology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; C440638:SPI-2 protein, Salmonella; C119761:SsrB protein, Salmonella typhimurium; D014157:Transcription Factors; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron