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Genetic and genomic approaches have been successfully used to assign genes to distinct regulatory networks. However, the present challenge of distinguishing differentially regulated genes within a network is particularly hard because members of a given network tend to have similar regulatory features. We have addressed this challenge by developing a method, termed Gene Promoter Scan, that discriminates coregulated promoters by simultaneously considering both multiple cis promoter features and ge

The PhoP/PhoQ two-component system is a master regulator of Salmonella pathogenicity. Here we report that induction of the PhoP/PhoQ system results in an initial surge of PhoP phosphorylation; the occupancy of target promoters by the PhoP protein; and the transcription of PhoP-activated genes, which then subsides to reach new steady-state levels. This surge in PhoP activity is due to PhoP positively activating its own transcription, because a strain constitutively expressing the PhoP protein att

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry and Biology of Ramoplanin: A Lipoglycodepsipeptide with Potent Antibiotic ActivitySuzanne Walker, Lan Chen, Yanan Hu, Yosup Rew, Dongwoo Shin, and Dale L. BogerView Author Information The Department of Microbiology & Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, The Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, and The Department of

Related organisms typically rely on orthologous regulatory proteins to respond to a given signal. However, the extent to which (or even if) the targets of shared regulatory proteins are maintained across species has remained largely unknown. This question is of particular significance in bacteria due to the widespread effects of horizontal gene transfer. Here, we address this question by investigating the regulons controlled by the DNA-binding PhoP protein, which governs virulence and Mg(2+) hom

Despite the fact that the regulatory system sensing density of cell population and its signaling molecule have been identified in Salmonella enterica, the biological significance of this phenomenon termed as quorum sensing remains unknown. In this report, we provide evidence that the luxS gene is necessary for Salmonella virulence phenotypes. Transcription assays showed that the cell-density-dependent induction of the invF gene was abolished in a Salmonella strain with the luxS gene deleted. The

We show that 3-[4-(4-methoxyphenyl)piperazin-1-yl]piperidin-4-yl biphenyl-4-carboxylate (C10), screened out of a chemical library, selectively kills bacterial persisters that tolerate antibiotic treatment but does not affect normal antibiotic-sensitive cells. C10 led persisters to antibiotic-induced cell death by causing reversion of persisters to antibiotic-sensitive cells. This work is the first demonstration in which the eradication of bacterial persisters is based on single-chemical suppleme

Low Mg2+ promotes phosphorylation of the response regulators PhoP and PmrA and transcription of their activated genes in Salmonella enterica. Using chromatin immunoprecipitation, we have now determined that the PhoP and PmrA proteins are recruited to the regulatory region of their target genes when bacteria experience low Mg2+ but not when they are grown in high Mg2+. Even when the PhoP protein was artificially produced at 4-fold higher levels than the wild-type strain, promoter occupancy requir

Bacterial cell-to-cell communication, termed quorum sensing (QS), controls bacterial behavior by using various signal molecules. Despite the fact that the LuxS/autoinducer-2 (AI-2) QS system is necessary for normal expression of Salmonella pathogenicity island-1 (SPI-1), the mechanism remains unknown. Here, we report that the LsrR protein, a transcriptional regulator known to be involved in LuxS/AI-2-mediated QS, is also associated with the regulation of SPI-1-mediated Salmonella virulence. We d

Reactive oxygen species (ROS) performs a pivotal function as a signaling mediator in receptor-mediated signaling. However, the sources of ROS in this signaling have yet to be determined, but may include lipoxygenases (LOXs) and NADPH oxidase. The stimulation of lymphoid cells with TNF-alpha, IL-1beta, and LPS resulted in significant ROS production and NF-kappaB activation. Intriguingly, these responses were markedly abolished via treatment with the LOXs inhibitor nordihydroguaiaretic acid (NDGA)

In the gammaproteobacteria, the FeoA, FeoB, and FeoC proteins constitute the Feo system, which mediates ferrous iron [Fe(II)] import. Of these Feo proteins, FeoB is an inner membrane Fe(II) transporter that is aided by the small protein FeoA. However, the role of another small protein, FeoC, has remained unknown. Here we report that the FeoC protein is necessary for FeoB protein-mediated Fe(II) uptake in Salmonella experiencing low levels of oxygen and iron. The FeoC protein was found to directl

Escherichia coli SdiA is a quorum-sensing (QS) receptor that responds to autoinducers produced by other bacterial species to control cell division and virulence. Crystal structures reveal that E. coli SdiA, which is composed of an N-terminal ligand-binding domain and a C-terminal DNA-binding domain (DBD), forms a symmetrical dimer. Although each domain shows structural similarity to other QS receptors, SdiA differs from them in the relative orientation of the two domains, suggesting that its lig

The PhoP/PhoQ two-component system controls several physiological and virulence functions in Salmonella enterica. This system is activated by low Mg(2+), acidic pH, and antimicrobial peptides, but the biological consequences resulting from sensing multiple signals are presently unclear. Here, we report that the PhoP/PhoQ system regulates different Salmonella genes depending on whether the inducing signal is acidic pH or low Mg(2+). When Salmonella experiences acidic pH, the PhoP/PhoQ system prom