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  1 / 3008 MEDLINE  
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PMID:29318906
Autor:Choi JJ; McCarthy MW
Endereço:a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
Título:Cefiderocol: a novel siderophore cephalosporin.
Fonte:Expert Opin Investig Drugs; 27(2):193-197, 2018 Feb.
ISSN:1744-7658
País de publicação:England
Idioma:eng
Resumo:INTRODUCTION: The emergence of multidrug-resistant bacterial pathogens has led to a global public health emergency and novel therapeutic options and drug-delivery systems are urgently needed. Cefiderocol is a siderophore cephalosporin antibiotic that has recently been developed to combat a variety of bacterial pathogens, including ß-lactam- and carbapenem-resistant organisms. Areas covered: This paper provides an overview of the mutational and plasmid-mediated mechanisms of ß-lactam and carbapenem resistance, the biochemical pathways of siderophores in bacterial iron metabolism, and how cefiderocol may be able to provide better targeted antimicrobial therapy that escape these drug-resistant mechanisms. We also explore the pharmacokinetics of this new compound as well as results from preclinical and clinical studies. Expert opinion: There is an urgent need for novel antimicrobial agents to address the emergence of multidrug-resistant pathogens, which are an increasing cause of morbidity and mortality worldwide. Our understanding of multidrug-resistance and bacterial biochemical pathways continues to expand, and the development of cefiderocol specifically targeting siderophore-mediated iron transport shows potential in escaping mechanisms of drug resistance. Cefiderocol, which demonstrates a favorable side effect profile, has the potential to become first-line therapy for our most aggressive and lethal multidrug-resistant Gram-negative pathogens.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Anti-Bacterial Agents); 0 (Cephalosporins); 0 (Siderophores); 0 (cefiderocol)


  2 / 3008 MEDLINE  
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PMID:29351296
Autor:Passera A; Marcolungo L; Casati P; Brasca M; Quaglino F; Cantaloni C; Delledonne M
Endereço:Department of Agricultural and Environmental Sciences - Production, Landscape, Agroenergy, Università degli Studi di Milano, Milan, Italy.
Título:Hybrid genome assembly and annotation of Paenibacillus pasadenensis strain R16 reveals insights on endophytic life style and antifungal activity.
Fonte:PLoS One; 13(1):e0189993, 2018.
ISSN:1932-6203
País de publicação:United States
Idioma:eng
Resumo:Bacteria of the Paenibacillus genus are becoming important in many fields of science, including agriculture, for their positive effects on the health of plants. However, there are little information available on this genus compared to other bacteria (such as Bacillus or Pseudomonas), especially when considering genomic information. Sequencing the genomes of plant-beneficial bacteria is a crucial step to identify the genetic elements underlying the adaptation to life inside a plant host and, in particular, which of these features determine the differences between a helpful microorganism and a pathogenic one. In this study, we have characterized the genome of Paenibacillus pasadenensis, strain R16, recently investigated for its antifungal activities and plant-associated features. An hybrid assembly approach was used integrating the very precise reads obtained by Illumina technology and long fragments acquired with Oxford Nanopore Technology (ONT) sequencing. De novo genome assembly based solely on Illumina reads generated a relatively fragmented assembly of 5.72 Mbp in 99 ungapped sequences with an N50 length of 544 Kbp; hybrid assembly, integrating Illumina and ONT reads, improved the assembly quality, generating a genome of 5.75 Mbp, organized in 6 contigs with an N50 length of 3.4 Mbp. Annotation of the latter genome identified 4987 coding sequences, of which 1610 are hypothetical proteins. Enrichment analysis identified pathways of particular interest for the endophyte biology, including the chitin-utilization pathway and the incomplete siderophore pathway which hints at siderophore parasitism. In addition the analysis led to the identification of genes for the production of terpenes, as for example farnesol, that was hypothesized as the main antifungal molecule produced by the strain. The functional analysis on the genome confirmed several plant-associated, plant-growth promotion, and biocontrol traits of strain R16, thus adding insights in the genetic bases of these complex features, and of the Paenibacillus genus in general.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Amino Sugars); 0 (DNA, Bacterial); 0 (Organic Chemicals); 0 (Siderophores)


  3 / 3008 MEDLINE  
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PMID:28463500
Autor:Kobylarz MJ; Heieis GA; Loutet SA; Murphy MEP
Endereço:The Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia , Vancouver, British Columbia V6T 1Z3; Canada.
Título:Iron Uptake Oxidoreductase (IruO) Uses a Flavin Adenine Dinucleotide Semiquinone Intermediate for Iron-Siderophore Reduction.
Fonte:ACS Chem Biol; 12(7):1778-1786, 2017 Jul 21.
ISSN:1554-8937
País de publicação:United States
Idioma:eng
Resumo:Many pathogenic bacteria including Staphylococcus aureus use iron-chelating siderophores to acquire iron. Iron uptake oxidoreductase (IruO), a flavin adenine dinucleotide (FAD)-containing nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase from S. aureus, functions as a reductase for IsdG and IsdI, two paralogous heme degrading enzymes. Also, the gene encoding for IruO was shown to be required for growth of S. aureus on hydroxamate siderophores as a sole iron source. Here, we show that IruO binds the hydroxamate-type siderophores desferrioxamine B and ferrichrome A with low micromolar affinity and in the presence of NADPH, Fe(II) was released. Steady-state kinetics of Fe(II) release provides k /K values in the range of 600 to 7000 M s for these siderophores supporting a role for IruO as a siderophore reductase in iron utilization. Crystal structures of IruO were solved in two distinct conformational states mediated by the formation of an intramolecular disulfide bond. A putative siderophore binding site was identified adjacent to the FAD cofactor. This site is partly occluded in the oxidized IruO structure consistent with this form being less active than reduced IruO. This reduction in activity could have a physiological role to limit iron release under oxidative stress conditions. Visible spectroscopy of anaerobically reduced IruO showed that the reaction proceeds by a single electron transfer mechanism through an FAD semiquinone intermediate. From the data, a model for single electron siderophore reduction by IruO using NADPH is described.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Benzoquinones); 0 (Siderophores); 146-14-5 (Flavin-Adenine Dinucleotide); 3225-29-4 (semiquinone radicals); 53-59-8 (NADP); E1UOL152H7 (Iron); EC 1.- (Oxidoreductases)


  4 / 3008 MEDLINE  
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PMID:28747481
Autor:O'Brien S; Luján AM; Paterson S; Cant MA; Buckling A
Endereço:Center for Adaptation to a Changing Environment (ACE), ETH Zürich, 8092 Zürich, Switzerland siobhan.obrien@env.ethz.ch.
Título:Adaptation to public goods cheats in .
Fonte:Proc Biol Sci; 284(1859), 2017 Jul 26.
ISSN:1471-2954
País de publicação:England
Idioma:eng
Resumo:Cooperation in nature is ubiquitous, but is susceptible to social cheats who pay little or no cost of cooperation yet reap the benefits. The effect such cheats have on reducing population productivity suggests that there is selection for cooperators to mitigate the adverse effects of cheats. While mechanisms have been elucidated for scenarios involving a direct association between producer and cooperative product, it is less clear how cooperators may suppress cheating in an anonymous public goods scenario, where cheats cannot be directly identified. Here, we investigate the real-time evolutionary response of cooperators to cheats when cooperation is mediated by a diffusible public good: the production of iron-scavenging siderophores by We find that siderophore producers evolved in the presence of a high frequency of non-producing cheats were fitter in the presence of cheats, at no obvious cost to population productivity. A novel morphotype independently evolved and reached higher frequencies in cheat-adapted versus control populations, exhibiting reduced siderophore production but increased production of pyocyanin-an extracellular toxin that can also increase the availability of soluble iron. This suggests that cooperators may have mitigated the negative effects of cheats by downregulating siderophore production and upregulating an alternative iron-acquisition public good. More generally, the study emphasizes that cooperating organisms can rapidly adapt to the presence of anonymous cheats without necessarily incurring fitness costs in the environment they evolve in.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Siderophores); E1UOL152H7 (Iron)


  5 / 3008 MEDLINE  
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PMID:28847923
Autor:Pasqua M; Visaggio D; Lo Sciuto A; Genah S; Banin E; Visca P; Imperi F
Endereço:Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Laboratory affiliated with Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, Italy.
Título:Ferric Uptake Regulator Fur Is Conditionally Essential in Pseudomonas aeruginosa.
Fonte:J Bacteriol; 199(22), 2017 Nov 15.
ISSN:1098-5530
País de publicação:United States
Idioma:eng
Resumo:In , the ferric uptake regulator (Fur) protein controls both metabolism and virulence in response to iron availability. Differently from other bacteria, attempts to obtain deletion mutants of failed, leading to the assumption that Fur is an essential protein in this bacterium. By investigating a conditional mutant, we demonstrate that Fur is not essential for growth in liquid media, biofilm formation, and pathogenicity in an insect model of infection. Conversely, Fur is essential for growth on solid media since Fur-depleted cells are severely impaired in colony formation. Transposon-mediated random mutagenesis experiments identified pyochelin siderophore biosynthesis as a major cause of the colony growth defect of the conditional mutant, and deletion mutagenesis confirmed this evidence. Impaired colony growth of pyochelin-proficient Fur-depleted cells does not depend on oxidative stress, since Fur-depleted cells do not accumulate higher levels of reactive oxygen species (ROS) and are not rescued by antioxidant agents or overexpression of ROS-detoxifying enzymes. Ectopic expression of genes revealed that pyochelin production has no inhibitory effects on a deletion mutant of pv. , suggesting that the toxicity of the locus in Fur-depleted cells involves a -specific pathway(s). Members of the ferric uptake regulator (Fur) protein family are bacterial transcriptional repressors that control iron uptake and storage in response to iron availability, thereby playing a crucial role in the maintenance of iron homeostasis. While null mutants of many bacteria have been obtained, Fur appears to be essential in for still unknown reasons. We obtained Fur-depleted cells by conditional mutagenesis and showed that Fur is dispensable for planktonic growth, while it is required for colony formation. This is because Fur protects colonies from toxicity exerted by the pyochelin siderophore. This work provides a functional basis to the essentiality of Fur in and highlights unique properties of the Fur regulon in this species.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Bacterial Proteins); 0 (Culture Media); 0 (Phenols); 0 (Reactive Oxygen Species); 0 (Repressor Proteins); 0 (Siderophores); 0 (Thiazoles); 0 (ferric uptake regulating proteins, bacterial); 69772-54-9 (pyochelin); E1UOL152H7 (Iron)


  6 / 3008 MEDLINE  
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PMID:28840714
Autor:Zhang F; Barns K; Hoffmann FM; Braun DR; Andes DR; Bugni TS
Título:Thalassosamide, a Siderophore Discovered from the Marine-Derived Bacterium Thalassospira profundimaris.
Fonte:J Nat Prod; 80(9):2551-2555, 2017 Sep 22.
ISSN:1520-6025
País de publicação:United States
Idioma:eng
Resumo:Here we describe the rapid identification and prioritization of novel active marine natural products using an improved dereplication strategy. During the course of our screening of marine natural product libraries, a new cyclic trihydroxamate compound, thalassosamide, was discovered from the α-proteobacterium Thalassospira profundimaris. Its structure was determined by 2D NMR and MS/MS experiments, and the absolute configuration of the lysine-derived units was established by Marfey's analysis, whereas that of C-9, 9', and 9″ was determined via the circular dichroism data of the [Rh (OCOCF ) ] complex and DFT NMR calculations. Thalassosamide showed moderate in vivo efficacy against Pseudomonas aeruginosa.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Biological Products); 0 (Hydroxamic Acids); 0 (Siderophores); 0 (thalassosamide)


  7 / 3008 MEDLINE  
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PMID:28791836
Autor:Kizilay G; Uz YH; Seren G; Ulucam E; Yilmaz A; Cukur Z; Kayisli UA
Endereço:Department of Histology and Embryology, Trakya University Faculty of Medicine, Edirne, Turkey.
Título:In vivo effects of curcumin and deferoxamine in experimental endometriosis.
Fonte:Adv Clin Exp Med; 26(2):207-213, 2017 Mar-Apr.
ISSN:1899-5276
País de publicação:Poland
Idioma:eng
Resumo:BACKGROUND: Endometriosis is one of the most common chronic gynecological diseases. OBJECTIVES: The aim of the study was to examine the effects of curcumin and/or deferoxamine on cell proliferation in a rat model of endometriosis. MATERIAL AND METHODS: Thirty female 12-week-old albino Wistar rats, weighing 200-250 g, were used in this study. All the rats underwent ovariectomy and 0.1-mg ß-estradiol 17-valerate pellets were placed intraperitoneally. An experimental model of endometriosis was created in all the animals. To create the experimental model, an approximately 1-cm long section of the uterus was taken, primarily from the right horn of the uterus. Autologous fragments were then placed between the peritoneum and muscle. The animals were divided into 3 groups: Group A, treated only with the vehicle used for curcumin and deferoxamine; group B, treated with curcumin (100 mg/kg body weight); and group C, treated with deferoxamine + curcumin (100 mg/kg body weight). After biopsy samples were obtained, the sections were stained with hematoxylin and eosin. Immunostaining for cytokeratin-7 and proliferating cell nuclear antigen (PCNA) was performed. Blood iron levels were measured using a Perkin Elmer AAnalyst 800 Atomic Absorption Spectrophotometer. RESULTS: The endometrial implant size increased in Group A, but treatment with curcumin (p = 0.01) and deferoxamine + curcumin (p = 0.007) reduced the implant size. In ectopic endometrial epithelial cells, there were significant decreases in PCNA immunoreactivity between groups A and B (p = 0.044) and between groups A and C (p = 0.033). CONCLUSIONS: Treatment with curcumin alone and/or in combination with deferoxamine contributed to a reduction in implant size and cell proliferation in a rat endometriosis model. Iron-chelating agents may act in the same manner when used in women with endometriosis; however, further studies from different perspectives are still needed.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Keratin-7); 0 (Proliferating Cell Nuclear Antigen); 0 (Siderophores); E1UOL152H7 (Iron); IT942ZTH98 (Curcumin); J06Y7MXW4D (Deferoxamine)


  8 / 3008 MEDLINE  
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PMID:28771547
Autor:Dutta J; Thakur D
Endereço:Microbial Biotechnology Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India.
Título:Evaluation of multifarious plant growth promoting traits, antagonistic potential and phylogenetic affiliation of rhizobacteria associated with commercial tea plants grown in Darjeeling, India.
Fonte:PLoS One; 12(8):e0182302, 2017.
ISSN:1932-6203
País de publicação:United States
Idioma:eng
Resumo:Plant growth promoting rhizobacteria (PGPR) are studied in different agricultural crops but the interaction of PGPR of tea crop is not yet studied well. In the present study, the indigenous tea rhizobacteria were isolated from seven tea estates of Darjeeling located in West Bengal, India. A total of 150 rhizobacterial isolates were screened for antagonistic activity against six different fungal pathogens i.e. Nigrospora sphaerica (KJ767520), Pestalotiopsis theae (ITCC 6599), Curvularia eragostidis (ITCC 6429), Glomerella cingulata (MTCC 2033), Rhizoctonia Solani (MTCC 4633) and Fusarium oxysporum (MTCC 284), out of which 48 isolates were antagonist to at least one fungal pathogen used. These 48 isolates exhibited multifarious antifungal properties like the production of siderophore, chitinase, protease and cellulase and also plant growth promoting (PGP) traits like IAA production, phosphate solubilization, ammonia and ACC deaminase production. Amplified ribosomal DNA restriction analysis (ARDRA) and BOX-PCR analysis based genotyping clustered the isolates into different groups. Finally, four isolates were selected for plant growth promotion study in two tea commercial cultivars TV-1 and Teenali-17 in nursery conditions. The plant growth promotion study showed that the inoculation of consortia of these four PGPR isolates significantly increased the growth of tea plant in nursery conditions. Thus this study underlines the commercial potential of these selected PGPR isolates for sustainable tea cultivation.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antifungal Agents); 0 (Bacterial Proteins); 0 (Calcium Phosphates); 0 (DNA, Fungal); 0 (Indoleacetic Acids); 0 (RNA, Ribosomal, 16S); 0 (Siderophores); 6U1S09C61L (indoleacetic acid); 7664-41-7 (Ammonia); EC 3.2.1.- (Glycoside Hydrolases); EC 3.2.1.14 (Chitinases); EC 3.2.1.4 (Cellulase); EC 3.5.99.7 (1-aminocyclopropane-1-carboxylate deaminase); EC 4.1.- (Carbon-Carbon Lyases); K4C08XP666 (tricalcium phosphate)


  9 / 3008 MEDLINE  
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PMID:28686889
Autor:Ma Y; Rajkumar M; Moreno A; Zhang C; Freitas H
Endereço:Centre for Functional Ecology, Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal. Electronic address: cathymaying@gmail.com.
Título:Serpentine endophytic bacterium Pseudomonas azotoformans ASS1 accelerates phytoremediation of soil metals under drought stress.
Fonte:Chemosphere; 185:75-85, 2017 Oct.
ISSN:1879-1298
País de publicação:England
Idioma:eng
Resumo:This study evaluates the potential of serpentine endophytic bacterium to foster phytoremediation efficiency of Trifolium arvense grown on multi-metal (Cu, Zn and Ni) contaminated soils under drought stress. A drought resistant endophytic bacterial strain ASS1 isolated from the leaves of Alyssum serpyllifolium grown in serpentine soils was identified as Pseudomonas azotoformans based on biochemical tests and partial 16S rRNA gene sequencing. P. azotoformans ASS1 possessed abiotic stress resistance (heavy metals, drought, salinity, antibiotics and extreme temperature) and plant growth promoting (PGP) properties (phosphate solubilization, nitrogen fixation, production of 1-aminocyclopropane-1-carboxylate deaminase, siderophore and ammonia). Inoculation of T. arvense with ASS1 considerably increased the plant biomass and leaf relative water content in both roll towel assay and pot experiments in the absence and presence of drought stress (DS). In the pot experiments, ASS1 greatly enhanced chlorophyll content, catalase, peroxidase, superoxide dismutase activities, and proline content (only in the absence of drought) in plant leaves, whereas they decreased the concentrations of malondialdehyde. Irrespective of water stress, ASS1 significantly improved accumulation, total removal, bio-concentration factor and biological accumulation coefficient of metals (Cu, Zn and Ni), while decreased translocation factors of Cu. The effective colonization and survival in the rhizosphere and tissue interior assured improved plant growth and successful metal phytoremediation under DS. These results demonstrate the potential of serpentine endophytic bacterium ASS1 for protecting plants against abiotic stresses and helping plants to thrive in semiarid ecosystems and accelerate phytoremediation process in metal polluted soils.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Asbestos, Serpentine); 0 (Metals, Heavy); 0 (RNA, Ribosomal, 16S); 0 (Siderophores); 0 (Soil); 0 (Soil Pollutants); EC 3.5.99.7 (1-aminocyclopropane-1-carboxylate deaminase); EC 4.1.- (Carbon-Carbon Lyases)


  10 / 3008 MEDLINE  
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PMID:28662060
Autor:Tjahjono E; Kirienko NV
Endereço:Department of BioSciences, Rice University, Houston, Texas, United States of America.
Título:A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa.
Fonte:PLoS Genet; 13(6):e1006876, 2017 Jun.
ISSN:1553-7404
País de publicação:United States
Idioma:eng
Resumo:All living organisms exist in a precarious state of homeostasis that requires constant maintenance. A wide variety of stresses, including hypoxia, heat, and infection by pathogens perpetually threaten to imbalance this state. Organisms use a battery of defenses to mitigate damage and restore normal function. Previously, we described a Caenorhabditis elegans-Pseudomonas aeruginosa assay (Liquid Killing) in which toxicity to the host is dependent upon the secreted bacterial siderophore pyoverdine. Although pyoverdine is also indispensable for virulence in mammals, its cytological effects are unclear. We used genetics, transcriptomics, and a variety of pathogen and chemical exposure assays to study the interactions between P. aeruginosa and C. elegans. Although P. aeruginosa can kill C. elegans through at least 5 different mechanisms, the defense responses activated by Liquid Killing are specific and selective and have little in common with innate defense mechanisms against intestinal colonization. Intriguingly, the defense response utilizes the phylogenetically-conserved ESRE (Ethanol and Stress Response Element) network, which we and others have previously shown to mitigate damage from a variety of abiotic stresses. This is the first report of this networks involvement in innate immunity, and indicates that host innate immune responses overlap with responses to abiotic stresses. The upregulation of the ESRE network in C. elegans is mediated in part by a family of bZIP proteins (including ZIP-2, ZIP-4, CEBP-1, and CEBP-2) that have overlapping and unique functions. Our data convincingly show that, following exposure to P. aeruginosa, the ESRE defense network is activated by mitochondrial damage, and that mitochondrial damage also leads to ESRE activation in mammals. This establishes a role for ESRE in a phylogenetically-conserved mitochondrial surveillance system important for stress response and innate immunity.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Basic-Leucine Zipper Transcription Factors); 0 (Oligopeptides); 0 (Siderophores); 0 (Virulence Factors); 8062-00-8 (pyoverdin)



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