4 research outputs found

    Structure and function of the Leptospira interrogans peroxide stress regulator (PerR), an atypical PerR devoid of a structural metal-binding site

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    International audiencePeroxide sensing is essential for bacterial survival during aerobic metabolism and host infection. Peroxide stress regulators (PerRs) are homodimeric transcriptional repressors with each monomer typically containing both structural and regulatory metal-binding sites. PerR binding to gene promoters is controlled by the presence of iron in the regulatory site, and iron-catalyzed oxidation of PerR by H2O2 leads to the dissociation of PerR from DNA. In addition to a regulatory metal, most PerRs require a structural metal for proper dimeric assembly. We present here a structural and functional characterization of the PerR from the pathogenic spirochete Leptospira interrogans, a rare example of PerR lacking a structural metal-binding site. In vivo studies showed that the leptospiral PerR belongs to the peroxide stimulon in pathogenic species and is involved in controlling resistance to peroxide. Moreover, a perR mutant had decreased fitness in other host-related stress conditions, including at 37 °C or in the presence of superoxide anion. In vitro, leptospiral PerR could bind to the perR promoter region in a metal-dependent manner. The crystal structure of the leptospiral PerR revealed an asymmetric homodimer, with one monomer displaying complete regulatory metal coordination in the characteristic caliper-like DNA-binding conformation and the second monomer exhibiting disrupted regulatory metal coordination in an open non-DNA-binding conformation. This structure showed that leptospiral PerR assembles into a dimer in which a metal-induced conformational switch can occur independently in the two monomers. Our study demonstrates that structural metal binding is not compulsory for PerR dimeric assembly and for regulating peroxide stress

    Variations in trihalomethane levels in three French water distribution systems and the development of a predictive model.

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    International audienceEpidemiological studies have demonstrated that chlorination by-products in drinking water may cause some types of cancer in humans. However, due to differences in methodology between the various studies, it is not possible to establish a dose-response relationship. This shortcoming is due primarily to uncertainties about how exposure is measured-made difficult by the great number of compounds present-the exposure routes involved and the variation in concentrations in water distribution systems. This is especially true for trihalomethanes for which concentrations can double between the water treatment plant and the consumer tap. The aim of this study is to describe the behaviour of trihalomethanes in three French water distribution systems and develop a mathematical model to predict concentrations in the water distribution system using data collected from treated water at the plant (i.e. the entrance of the distribution system). In 2006 and 2007, samples were taken successively from treated water at the plant and at several points in the water distribution system in three French cities. In addition to the concentrations of the four trihalomethanes (chloroform, dichlorobromomethane, chlorodibromomethane, bromoform), many other parameters involved in their formation that affect their concentration were also measured. The average trihalomethane concentration in the three water distribution systems ranged from 21.6 μg/L to 59.9 μg/L. The increase in trihalomethanes between the treated water at the plant and a given point in the water distribution system varied by a factor of 1.1-5.7 over all of the samples. A log-log linear regression model was constructed to predict THM concentrations in the water distribution system. The five variables used were trihalomethane concentration and free residual chlorine for treated water at the plant, two variables that characterize the reactivity of organic matter (specific UV absorbance (SUVA), an indicator developed for the free chlorine consumption in the treatment plant before distribution δ) and water residence time in the distribution system. French regulations impose a minimum trihalomethane level for drinking water and most tests are performed on treated water at the plant. Applied in this context, the model developed here helps better to understand trihalomethane exposure in the French population, particularly useful for epidemiological studies
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