1,721,083 research outputs found
Deregulation of transition metals homeostasis is a key feature of cadmium toxicity in Salmonella
No full textCadmium is a highly toxic metal whose presence in the environment represents a challenge for all forms of life. To improve our knowledge on cadmium toxicity, we have explored Salmonella Typhimurium responses to this metal. We have found that cadmium induces the concomitant expression of the cation efflux pump ZntA and of the high affinity zinc import system ZnuABC. This observation suggests that cadmium accumulation within the cell induces a condition of apparent zinc starvation, possibly due to the ability of this metal to compete with zinc for the metal binding site of proteins. This hypothesis is supported by the finding that strains lacking ZntA or ZnuABC are hyper-susceptible to cadmium and that the cadmium-induced growth defect of a znuABC mutant strain is largely relieved by zinc supplementation. A similar growth defect was observed for a mutant with impaired ability to acquire iron, whereas cadmium does not affect growth of a strain defective in manganese import. Cadmium also influences the expression and activity of the two cytoplasmic superoxide dismutases FeSOD and MnSOD, which are required to control cadmium-mediate oxidative stress. Exposure to cadmium causes a reduction of FeSOD activity in Salmonella wild type and the complete abrogation of its expression in the strain defective in iron import. In contrast, although MnSOD intracellular levels increase in response to cadmium, we observed discrepancies between protein levels and enzymatic activity which are suggestive of incorporation of non-catalytic metals in the active site or to cadmium-mediated inhibition of manganese import. Our results indicate that cadmium interferes with the ability of cells to manage transition metals and highlight the close interconnections between the homeostatic mechanisms regulating the intracellular levels of different metals
Editorial: Dealing with unusual hosts and unconventional habitats: versatile strategies of Salmonella enterica
No full textDifferences in gene expression levels and in enzymatic qualities account for the uneven contribution of superoxide dismutases SodCI and SodCII to pathogenicity in Salmonella enterica
No full textMost Salmonella enterica serovars produce two periplasmic [Cu,Zn] superoxide dismutases, SodCI, which is prophage encoded, and SodCII, encoded by a conserved chromosomal gene. Both enzymes were proposed to enhance Salmonella virulence by protecting bacteria against products of macrophage oxidative burst. However, we previously found SodCI, but not SodCII, to play a role during mouse infection by S. enterica serovar Typhimurium. Here we have extended these findings to another serovar of epidemiological relevance: sv Enteritidis. In both serovars, the dominant role of SodCI in virulence correlates with its higher levels in bacteria proliferating in mouse tissues, relative to SodCII. To analyze the basis of these differences, the coding sequences of sodCI and sodCII genes were exchanged with the reciprocal 5'-regions (in serovar Typhimurium). The accumulation patterns of the two proteins in vivo were reversed as a result, indicating that the regulatory determinants lie entirely within the regions upstream from the initiation codon. In the construct with the sodCI gene fused to the sodCII 5'-region, SodCl contribution to virulence was reduced but remained significant. Thus, both, high-level expression and some unidentified qualities of the enzyme participate in the phenotypic dominance of SodCI over SodCII in Salmonella pathogenicity. (c) 2006 Elsevier SAS. All rights reserved
Competition for zinc binding in the host-pathogen interaction
Full text linkDue to its favorable chemical properties, zinc is used as a structural or catalytic cofactor in a very large number of proteins. Despite the apparent abundance of this metal in all cell types, the intracellular pool of loosely bound zinc ions available for biological exchanges is in the picomolar range and nearly all zinc is tightly bound to proteins. In addition, to limit bacterial growth, some zinc-sequestering proteins are produced by eukaryotic hosts in response to infections. Therefore, to grow and multiply in the infected host, bacterial pathogens must produce high affinity zinc importers, such as the ZnuABC transporter which is present in most Gram-negative bacteria. Studies carried in different bacterial species have established that disruption of ZnuABC is usually associated with a remarkable loss of pathogenicity. The critical involvement of zinc in a plethora of metabolic and virulence pathways and the presence of very low number of zinc importers in most bacterial species mark zinc homeostasis as a very promising target for the development of novel antimicrobial strategies
Cobalt can fully recover the phenotypes related to zinc deficiency in Salmonella Typhimurium
No full textCobalt is an essential element for living systems, which, however, make very limited use of this metal, using it mainly in cobalamin-containing enzymes. The reduced use of cobalt compared to other transition metals is generally attributed to the potential toxicity of this element. In this work, we demonstrate that cobalt not only does not have an obvious toxic effect on Salmonella Typhimurium, but that it can efficiently compensate for zinc deficiency in a znuABC deleted strain. In fact, cobalt, but not cobalamin supplementation, rescued all major phenotypic defects of the znuABC strain, including the reduced ability to grow and swim in zinc-deficient media and the high susceptibility to hydrogen peroxide stress. Growth in a cobalt-supplemented defined medium led to the accumulation of large amounts of cobalt both in the wild type and in the znuABC strain. These data suggest that atoms of cobalt may be incorporated in bacterial proteins in place of zinc, ensuring their functionality. In support of this hypothesis we have shown that, in vivo, cobalt can accumulate in ribosomes and replace zinc in a periplasmic Cu,Zn superoxide dismutase (SodCII). Finally, we provide evidence of the ability of cobalt to modulate the intracellular concentration of zinc-regulated proteins (ZnuA, ZinT, and SodCII). Although some observations suggest that in some proteins the replacement of zinc with cobalt can lead to subtle structural changes, the data reported in this study indicate that Salmonella has the ability to use cobalt instead of zinc, without evident harmful effects for cell physiology
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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