The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Harry L. T. Mobley - One of the best experts on this subject based on the ideXlab platform.
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Proteobactin and a yersiniabactin-related Siderophore mediate iron acquisition in Proteus mirabilis
Molecular Microbiology, 2010Co-Authors: Stephanie D. Himpsl, Melanie M. Pearson, Carl J. Arewång, Tyler D. Nusca, David H. Sherman, Harry L. T. MobleyAbstract:Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an iron-limiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes ( P ≤ 0.05) that represent 21 putative iron-regulated systems. Two gene clusters, PMI0229-0239 and PMI2596-2605, encode putative Siderophore systems. PMI0229-0239 encodes a non-ribosomal peptide synthetase-independent Siderophore system for producing a novel Siderophore, proteobactin. PMI2596-2605 are contained within the high-pathogenicity island, originally described in Yersinia pestis , and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross-feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin-related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron-chelating defect; demonstrating production and iron-chelating activity for both Siderophores. These findings clearly show that proteobactin and the yersiniabactin-related Siderophore function as iron acquisition systems. Despite the activity of both Siderophores, only mutants lacking the yersiniabactin-related Siderophore have reduced fitness in vivo . The fitness requirement for the yersiniabactin-related Siderophore during UTI shows, for the first time, the importance of Siderophore production in vivo for P. mirabilis
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Proteobactin and a yersiniabactin‐related Siderophore mediate iron acquisition in Proteus mirabilis
Molecular microbiology, 2010Co-Authors: Stephanie D. Himpsl, Melanie M. Pearson, Carl J. Arewång, Tyler D. Nusca, David H. Sherman, Harry L. T. MobleyAbstract:Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an iron-limiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes (P ≤ 0.05) that represent 21 putative iron-regulated systems. Two gene clusters, PMI0229-0239 and PMI2596-2605, encode putative Siderophore systems. PMI0229-0239 encodes a non-ribosomal peptide synthetase-independent Siderophore system for producing a novel Siderophore, proteobactin. PMI2596-2605 are contained within the high-pathogenicity island, originally described in Yersinia pestis, and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross-feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin-related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron-chelating defect; demonstrating production and iron-chelating activity for both Siderophores. These findings clearly show that proteobactin and the yersiniabactin-related Siderophore function as iron acquisition systems. Despite the activity of both Siderophores, only mutants lacking the yersiniabactin-related Siderophore have reduced fitness in vivo. The fitness requirement for the yersiniabactin-related Siderophore during UTI shows, for the first time, the importance of Siderophore production in vivo for P. mirabilis.
Steven D. Bruner - One of the best experts on this subject based on the ideXlab platform.
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Microbial Siderophore-based iron assimilation and therapeutic applications
BioMetals, 2016Co-Authors: Kunhua Li, Wei-hung Chen, Steven D. BrunerAbstract:Siderophores are structurally diverse, complex natural products that bind metals with extraordinary specificity and affinity. The acquisition of iron is critical for the survival and virulence of many pathogenic microbes and diverse strategies have evolved to synthesize, import and utilize iron. There has been a substantial increase of known Siderophore scaffolds isolated and characterized in the past decade and the corresponding biosynthetic gene clusters have provided insight into the varied pathways involved in Siderophore biosynthesis, delivery and utilization. Additionally, therapeutic applications of Siderophores and related compounds are actively being developed. The study of biosynthetic pathways to natural Siderophores augments the understanding of the complex mechanisms of bacterial iron acquisition, and enables a complimentary approach to address virulence through the interruption of Siderophore biosynthesis or utilization by targeting the key enzymes to the Siderophore pathways.
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structure and mechanism of the Siderophore interacting protein from the fuscachelin gene cluster of thermobifida fusca
Biochemistry, 2015Co-Authors: Wei-hung Chen, Steven D. BrunerAbstract:Microbial iron acquisition is a complex process and frequently a key and necessary step for survival. Among the several paths for iron assimilation, small molecule Siderophore-mediated transport is a commonly employed strategy of many microorganisms. The chemistry and biology of the extraordinary tight and specific binding of Siderophores to metal is also exploited in therapeutic treatments for microbial virulence and metal toxicity. The intracellular fate of iron acquired via the Siderophore pathway is one of the least understood steps in the complex process at the molecular level. A common route to cellular incorporation is the single-electron reduction of ferric to ferrous iron catalyzed by specific and/or nonspecific reducing agents. The biosynthetic gene clusters for Siderophores often contain representatives of one or two families of redox-active enzymes: the flavin-containing "Siderophore-interacting protein" and iron-sulfur ferric Siderophore reductases. Here we present the structure and characterization of the Siderophore-interacting protein, FscN, from the fuscachelin Siderophore gene cluster of Thermobifida fusca. The structure shows a flavoreductase fold with a noncovalently bound FAD cofactor along with an unexpected metal bound adjacent to the flavin site. We demonstrated that FscN is redox-active and measured the binding and reduction of ferric fuscachelin. This work provides a structural basis for the activity of a Siderophore-interacting protein and further insight into the complex and important process of iron acquisition and utilization.
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Structure and Mechanism of the Siderophore-Interacting Protein from the Fuscachelin Gene Cluster of Thermobifida fusca
2015Co-Authors: Wei-hung Chen, Steven D. BrunerAbstract:Microbial iron acquisition is a complex process and frequently a key and necessary step for survival. Among the several paths for iron assimilation, small molecule Siderophore-mediated transport is a commonly employed strategy of many microorganisms. The chemistry and biology of the extraordinary tight and specific binding of Siderophores to metal is also exploited in therapeutic treatments for microbial virulence and metal toxicity. The intracellular fate of iron acquired via the Siderophore pathway is one of the least understood steps in the complex process at the molecular level. A common route to cellular incorporation is the single-electron reduction of ferric to ferrous iron catalyzed by specific and/or nonspecific reducing agents. The biosynthetic gene clusters for Siderophores often contain representatives of one or two families of redox-active enzymes: the flavin-containing “Siderophore-interacting protein” and iron–sulfur ferric Siderophore reductases. Here we present the structure and characterization of the Siderophore-interacting protein, FscN, from the fuscachelin Siderophore gene cluster of Thermobifida fusca. The structure shows a flavoreductase fold with a noncovalently bound FAD cofactor along with an unexpected metal bound adjacent to the flavin site. We demonstrated that FscN is redox-active and measured the binding and reduction of ferric fuscachelin. This work provides a structural basis for the activity of a Siderophore-interacting protein and further insight into the complex and important process of iron acquisition and utilization
Angus Buckling - One of the best experts on this subject based on the ideXlab platform.
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ecological selection of Siderophore producing microbial taxa in response to heavy metal contamination
Ecology Letters, 2018Co-Authors: Elze Hesse, S Obrien, Nicolas Tromas, Florian Bayer, Adela M Lujan, Eleanor Van Veen, Dave J Hodgson, Angus BucklingAbstract:Some microbial public goods can provide both individual and community-wide benefits, and are open to exploitation by non-producing species. One such example is the production of metal-detoxifying Siderophores. Here, we investigate whether conflicting selection pressures on Siderophore production by heavy metals - a detoxifying effect of Siderophores, and exploitation of this detoxifying effect - result in a net increase or decrease. We show that the proportion of Siderophore-producing taxa increases along a natural heavy metal gradient. A causal link between metal contamination and Siderophore production was subsequently demonstrated in a microcosm experiment in compost, in which we observed changes in community composition towards taxa that produce relatively more Siderophores following copper contamination. We confirmed the selective benefit of Siderophores by showing that taxa producing large amounts of Siderophore suffered less growth inhibition in toxic copper. Our results suggest that ecological selection will favour Siderophore-mediated decontamination, with important consequences for potential remediation strategies.
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ecological selection of Siderophore producing microbial taxa in response to heavy metal contamination
bioRxiv, 2017Co-Authors: Elze Hesse, S Obrien, Nicolas Tromas, Florian Bayer, Adela M Lujan, Eleanor Van Veen, Dave J Hodgson, Angus BucklingAbstract:Some microbial public goods can provide both individual and community-wide benefits, and are open to exploitation by non-producing species. One such example is the production of metal-detoxifying Siderophores. Here, we investigate whether heavy metals select for increased Siderophore production in natural microbial communities, or whether exploitation of this detoxifying effect reduces Siderophore production. We show that the proportion of Siderophore-producing taxa increases along a natural heavy metal gradient. A causal link between metal contamination and Siderophore production was subsequently demonstrated in a microcosm experiment in compost, in which we observed changes in community composition towards taxa that produce relatively more Siderophores following copper contamination. We confirmed the selective benefit of Siderophores by showing that taxa producing large amount of Siderophores suffered less growth inhibition in toxic copper. Our results suggest that ecological selection will favour Siderophore-mediated decontamination, with important consequences for potential remediation strategies.
Stephanie D. Himpsl - One of the best experts on this subject based on the ideXlab platform.
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Proteobactin and a yersiniabactin-related Siderophore mediate iron acquisition in Proteus mirabilis
Molecular Microbiology, 2010Co-Authors: Stephanie D. Himpsl, Melanie M. Pearson, Carl J. Arewång, Tyler D. Nusca, David H. Sherman, Harry L. T. MobleyAbstract:Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an iron-limiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes ( P ≤ 0.05) that represent 21 putative iron-regulated systems. Two gene clusters, PMI0229-0239 and PMI2596-2605, encode putative Siderophore systems. PMI0229-0239 encodes a non-ribosomal peptide synthetase-independent Siderophore system for producing a novel Siderophore, proteobactin. PMI2596-2605 are contained within the high-pathogenicity island, originally described in Yersinia pestis , and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross-feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin-related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron-chelating defect; demonstrating production and iron-chelating activity for both Siderophores. These findings clearly show that proteobactin and the yersiniabactin-related Siderophore function as iron acquisition systems. Despite the activity of both Siderophores, only mutants lacking the yersiniabactin-related Siderophore have reduced fitness in vivo . The fitness requirement for the yersiniabactin-related Siderophore during UTI shows, for the first time, the importance of Siderophore production in vivo for P. mirabilis
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Proteobactin and a yersiniabactin‐related Siderophore mediate iron acquisition in Proteus mirabilis
Molecular microbiology, 2010Co-Authors: Stephanie D. Himpsl, Melanie M. Pearson, Carl J. Arewång, Tyler D. Nusca, David H. Sherman, Harry L. T. MobleyAbstract:Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an iron-limiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes (P ≤ 0.05) that represent 21 putative iron-regulated systems. Two gene clusters, PMI0229-0239 and PMI2596-2605, encode putative Siderophore systems. PMI0229-0239 encodes a non-ribosomal peptide synthetase-independent Siderophore system for producing a novel Siderophore, proteobactin. PMI2596-2605 are contained within the high-pathogenicity island, originally described in Yersinia pestis, and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross-feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin-related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron-chelating defect; demonstrating production and iron-chelating activity for both Siderophores. These findings clearly show that proteobactin and the yersiniabactin-related Siderophore function as iron acquisition systems. Despite the activity of both Siderophores, only mutants lacking the yersiniabactin-related Siderophore have reduced fitness in vivo. The fitness requirement for the yersiniabactin-related Siderophore during UTI shows, for the first time, the importance of Siderophore production in vivo for P. mirabilis.
Adela M Lujan - One of the best experts on this subject based on the ideXlab platform.
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ecological selection of Siderophore producing microbial taxa in response to heavy metal contamination
Ecology Letters, 2018Co-Authors: Elze Hesse, S Obrien, Nicolas Tromas, Florian Bayer, Adela M Lujan, Eleanor Van Veen, Dave J Hodgson, Angus BucklingAbstract:Some microbial public goods can provide both individual and community-wide benefits, and are open to exploitation by non-producing species. One such example is the production of metal-detoxifying Siderophores. Here, we investigate whether conflicting selection pressures on Siderophore production by heavy metals - a detoxifying effect of Siderophores, and exploitation of this detoxifying effect - result in a net increase or decrease. We show that the proportion of Siderophore-producing taxa increases along a natural heavy metal gradient. A causal link between metal contamination and Siderophore production was subsequently demonstrated in a microcosm experiment in compost, in which we observed changes in community composition towards taxa that produce relatively more Siderophores following copper contamination. We confirmed the selective benefit of Siderophores by showing that taxa producing large amounts of Siderophore suffered less growth inhibition in toxic copper. Our results suggest that ecological selection will favour Siderophore-mediated decontamination, with important consequences for potential remediation strategies.
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ecological selection of Siderophore producing microbial taxa in response to heavy metal contamination
bioRxiv, 2017Co-Authors: Elze Hesse, S Obrien, Nicolas Tromas, Florian Bayer, Adela M Lujan, Eleanor Van Veen, Dave J Hodgson, Angus BucklingAbstract:Some microbial public goods can provide both individual and community-wide benefits, and are open to exploitation by non-producing species. One such example is the production of metal-detoxifying Siderophores. Here, we investigate whether heavy metals select for increased Siderophore production in natural microbial communities, or whether exploitation of this detoxifying effect reduces Siderophore production. We show that the proportion of Siderophore-producing taxa increases along a natural heavy metal gradient. A causal link between metal contamination and Siderophore production was subsequently demonstrated in a microcosm experiment in compost, in which we observed changes in community composition towards taxa that produce relatively more Siderophores following copper contamination. We confirmed the selective benefit of Siderophores by showing that taxa producing large amount of Siderophores suffered less growth inhibition in toxic copper. Our results suggest that ecological selection will favour Siderophore-mediated decontamination, with important consequences for potential remediation strategies.
