Hydrogen peroxide triggers an increase in cell surface expression of system x in cultured human glioma cells.

System x exchanges extracellular cystine for intracellular glutamate across the plasma membrane of many cell types. One of the physiological roles of System x is to provide cystine for synthesis of the antioxidant glutathione. Here we report that hydrogen peroxide (HO) triggers the translocation of System x to the plasma membrane within 10 min of the initial exposure.

The C terminus of the bacterial multidrug transporter EmrE couples drug binding to proton release.

Ion-coupled transporters must regulate access of ions and substrates into and out of the binding site to actively transport substrates and minimize dissipative leak of ions. Within the single-site alternating access model, competitive substrate binding forms the foundation of ion-coupled antiport. Strict competition between substrates leads to stoichiometric antiport without slippage.

Uropathogenic enterobacteria use the yersiniabactin metallophore system to acquire nickel.

Invasive Gram-negative bacteria often express multiple virulence-associated metal ion chelators to combat host-mediated metal deficiencies. , , and isolates encoding the high pathogenicity island (HPI) secrete yersiniabactin (Ybt), a metallophore originally shown to chelate iron ions during infection. However, our recent demonstration that Ybt also scavenges copper ions during infection led us to question whether it might be capable of retrieving other metals as well.

The iron hand of uropathogenic Escherichia coli: the role of transition metal control in virulence.

The role of iron as a critical nutrient in pathogenic bacteria is widely regarded as having driven selection for iron acquisition systems among uropathogenic Escherichia coli (UPEC) isolates. Carriage of multiple transition metal acquisition systems in UPEC suggests that the human urinary tract manipulates metal-ion availability in many ways to resist infection. For siderophore systems in particular, recent studies have identified new roles for siderophore copper binding as well as production of siderophore-like inhibitors of iron uptake by other, competing bacterial species.

A mass spectrometry based transport assay for studying EmrE transport of unlabeled substrates.

Membrane transporters are an important class of proteins which remain challenging to study. Transport assays are crucial to developing our understanding of such proteins as they allow direct measurement of their transport activity. However, currently available methods for monitoring liposomal loading of organic substrates primarily rely on detection of radioactively or fluorescently labeled substrates.

New free-exchange model of EmrE transport.

EmrE is a small multidrug resistance transporter found in that confers resistance to toxic polyaromatic cations due to its proton-coupled antiport of these substrates. Here we show that EmrE breaks the rules generally deemed essential for coupled antiport. NMR spectra reveal that EmrE can simultaneously bind and cotransport proton and drug.

Copper import in Escherichia coli by the yersiniabactin metallophore system.

Copper plays a dual role as a nutrient and a toxin during bacterial infections. While uropathogenic Escherichia coli (UPEC) strains can use the copper-binding metallophore yersiniabactin (Ybt) to resist copper toxicity, Ybt also converts bioavailable copper to Cu(II)-Ybt in low-copper conditions. Although E.

Asymmetric protonation of EmrE.

The small multidrug resistance transporter EmrE is a homodimer that uses energy provided by the proton motive force to drive the efflux of drug substrates. The pKa values of its "active-site" residues--glutamate 14 (Glu14) from each subunit--must be poised around physiological pH values to efficiently couple proton import to drug export in vivo. To assess the protonation of EmrE, pH titrations were conducted with (1)H-(15)N TROSY-HSQC nuclear magnetic resonance (NMR) spectra.

Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis.

Background: Despite substantial decreases in recent decades, acute gastroenteritis causes the second greatest burden of all infectious diseases worldwide. Noroviruses are a leading cause of sporadic cases and outbreaks of acute gastroenteritis across all age groups. We aimed to assess the role of norovirus as a cause of endemic acute gastroenteritis worldwide.