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We found herein that the intracytoplasmic pool of the low-molecular-weight (LMW) thiol glutathione (GSH) is readily oxidized in Salmonella exposed to nitric oxide (NO). The hypersusceptibility of gshA and gshB mutants lacking γ-glutamylcysteine and glutathione synthetases to NO and S-nitrosoglutathione indicates that GSH antagonizes the bacteriostatic(More)
Our investigations have identified a mechanism by which exogenous production of nitric oxide (NO) induces resistance of Gram-positive and -negative bacteria to aminoglycosides. An NO donor was found to protect Salmonella spp. against structurally diverse classes of aminoglycosides of the 4,6-disubstituted 2-deoxystreptamine group. Likewise, NO generated(More)
Aerobic metabolism generates biologically challenging reactive oxygen species (ROS) by the endogenous autooxidation of components of the electron transport chain (ETC). Basal levels of oxidative stress can dramatically rise upon activation of the NADPH oxidase-dependent respiratory burst. To minimize ROS toxicity, prokaryotic and eukaryotic organisms(More)
The bactericidal activity of moxifloxacin alone and in combination with cefepime or piperacillin-tazobactam against clinical isolates of Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii was evaluated by using time-kill methods and antimicrobial concentrations of one-half and one times the MIC. Synergy was observed in 58 to 88% of the(More)
We show here that the nitric oxide (NO)-detoxifying Hmp flavohemoprotein increases by 3-fold the transcription of the Salmonella pathogenicity island 2 (SPI2) in macrophages expressing a functional inducible NO synthase (iNOS). However, Hmp does not prevent NO-related repression of SPI2 transcription in IFNgamma-primed phagocytes, despite preserving(More)
We show that thiols in the 4-cysteine zinc-finger motif of DksA, an RNA polymerase accessory protein known to regulate the stringent response, sense oxidative and nitrosative stress. Hydrogen peroxide- or nitric oxide (NO)-mediated modifications of thiols in the DksA 4-cysteine zinc-finger motif release the metal cofactor and drive reversible changes in the(More)
Intracellular Ca2+ transients have been shown to control several transition points within the eukaryotic cell cycle. We focus here on the G1-to-S phase transition triggered by an increase in the intracellular Ca2+ concentration ([Ca2+](i)) in rodent vascular smooth muscle cells (VSMC) and its potential targeting for the treatment of vaso-occlusive processes(More)
We demonstrate that two Myb-binding sites of the mouse plasma membrane Ca(2+)-ATPase-1 (PMCA1) promoter are required for G(1)/S cell cycle stage-associated repression of PMCA1 promoter activity. Nuclear run-on experiments revealed G(1)/S-associated repression of PMCA1 transcription. Ribonuclease protection assays revealed two transcription initiation sites(More)
We show herein that the Salmonella pathogenicity island 2 (SPI2) response regulator SsrB undergoes S-nitrosylation upon exposure of Salmonella to acidified nitrite, a signal encountered by this enteropathogen in phagosomes of macrophages. Mutational analysis has identified Cys(203) in the C-terminal dimerization domain of SsrB as the redox-active residue(More)
Herein we report an important role for the ferric uptake regulator (Fur) in the resistance of Salmonella enterica serovar Typhimurium to the reactive nitrogen species produced by inducible nitric oxide (NO) synthase in an NRAMP1(r) murine model of acute systemic infection. The expression of fur protected Salmonella grown under normoxic and hypoxic(More)