PMID:22210763
Citation |
Warner, DM and Levy, SB (2012) SoxS increases the expression of the zinc uptake system ZnuACB in an Escherichia coli murine pyelonephritis model. J. Bacteriol. 194:1177-85 |
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Abstract |
Paralogous transcriptional regulators MarA, Rob, and SoxS act individually and together to control expression of more than 80 Escherichia coli genes. Deletion of marA, rob, and soxS from an E. coli clinical isolate prevents persistence beyond 2 days postinfection in a mouse model of pyelonephritis. We used microarray analysis to identify 242 genes differentially expressed between the triple deletion mutant and its parent strain at 2 days postinfection in the kidney. One of these, znuC of the zinc transport system ZnuACB, displayed decreased expression in the triple mutant compared to that in the parental strain, and deletion of znuC from the parental strain reduced persistence. The marA rob soxS triple deletion mutant was less viable in vitro under limited-Zn and Zn-depleted conditions, while disruption of znuC caused a reduction in the growth rates for the parental and triple mutant strains to equally low levels under limited-Zn or Zn-depleted conditions. Complementation of the triple mutant with soxS, but not marA or rob, restored the parental growth rate in Zn-depleted medium, while deletion of only soxS from the parental strain led to low growth in Zn-depleted medium. Both results suggested that SoxS is a major regulator responsible for growth under Zn-depleted conditions. Gel shift experiments failed to show direct binding of SoxS to the znuCB promoter, thus suggesting indirect control of znuCB expression by SoxS. While SoxS expression in the triple mutant fully restored persistence, increased expression of znuACB via a plasmid in this mutant only partially restored wild-type levels of persistence in the kidney. This work implicates SoxS control of znuCB expression as a key factor in persistence of E. coli in murine pyelonephritis. |
Links |
PubMed PMC3294818 Online version:10.1128/JB.05451-11 |
Keywords |
ATP-Binding Cassette Transporters/biosynthesis; Animals; Cation Transport Proteins/biosynthesis; Disease Models, Animal; Electrophoretic Mobility Shift Assay; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Infections/microbiology; Escherichia coli Proteins/biosynthesis; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genetic Complementation Test; Mice; Microarray Analysis; Pyelonephritis/microbiology; Trans-Activators/genetics; Trans-Activators/metabolism; Zinc/metabolism |
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