1,721,034 research outputs found
The genomics of Acinetobacter baumannii: Insights into genome plasticity, antimicrobial resistance and pathogenicity
No full textImperi F, Antunes L, Blom J, et al. The genomics of Acinetobacter baumannii: Insights into genome plasticity, antimicrobial resistance and pathogenicity. IUBMB life. 2011;63(12):1068-1074
Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin
No full textInvolvement of AlgQ in transcriptional regulation of pyoverdine genes in Pseudomonas aeruginosa PAO1
No full textEffect of siderophores and iron chelators on gallium inhibitory activity in Pseudomonas aeruginosa
No full textSubcellular localization of the pyoverdine biogenesis machinery of Pseudomonas aeruginosa: a membrane-associated "siderosome"
No full textThe peptidic siderophore pyoverdine is the primary iron uptake system of fluorescent pseudomonads, and a virulence factor in the opportunistic pathogen Pseudomonas aeruginosa. Pyoverdine biogenesis is a co-ordinate process requiring several precursor-generating enzymes and large nonribosomal peptide synthetases (NRPSs) in the cytoplasm, followed by extracytoplasmic maturation. By using cell fractionation, protein-protein interaction, and in vivo labeling assays we obtained evidence that, in P. aeruginosa, pyoverdine NRPSs assemble with precursor-generating enzymes into a membrane-bound multi-enzymatic complex, for which we propose the name "siderosome". The pyoverdine biogenetic complex represents a novel example of subcellular compartmentalization of a secondary metabolic pathway in prokaryotes
In vitro and in vivo antimicrobial activities of gallium nitrate against multidrug-resistant Acinetobacter baumannii
No full textMultidrug-resistant Acinetobacter baumannii poses a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumannii chemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO(3))(3), the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58 A. baumannii strains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO(3))(3) delayed the entry of A. baumannii into the exponential phase and drastically reduced bacterial growth rates. Ga(NO(3))(3) activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO(3))(3) also protected Galleria mellonella larvae from lethal A. baumannii infection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO(3))(3) inhibited the growth in human serum of 76% of the multidrug-resistant A. baumannii isolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment of A. baumannii bloodstream infections. Ga(NO(3))(3) also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistant A. baumannii
Genome-assisted identification of putative iron-utilization genes in Acinetobacter baumannii and their distribution among a genotypically diverse collection of clinical isolates
No full textNew putative iron-uptake genes were identified in published genomes of the opportunistic human pathogen Acinetobacter baumannii, and their occurrence was determined in a genotypically distinct collection of 50 clinical isolates by PCR and Southern blot assays. The results demonstrated that all A. baumannii isolates tested share the coding potential for two endogenous siderophores, a heme-acquisition and a ferrous iron-uptake system. A second heme-uptake cluster was detected in almost two thirds of isolates, without any apparent correlation with the clonal lineage of the strains. The wide distribution of multiple iron-acquisition systems among diverse A. baumannii clinical isolates argues for a contribution of iron uptake to the pathogenicity of this species. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved
Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin
Full text linkHuman serum albumin (HSA) participates to heme scavenging, in turn HSA-heme binds gaseous diatomic ligands at the heme-Fe-atom. Here, the effect of abacavir and warfarin on denitrosylation kinetics of HSA-heme Fe(II)-NO (i.e., k(off)) is reported. In the absence of drugs, the value of k(off) is (1.3 +/- 0.2) x 10(-4) s(-1). Abacavir and warfarin facilitate NO dissociation from HSA-heme-Fe(II)-NO, the k(off) value increases to (8.6 +/- 0.9) x 10(-4) s(-1). From the dependence of k(off) on the drug concentration, values of the dissociation equilibrium constant for the abacavir and warfarin binding to HSA-heme-Fe(II)-NO (i.e., K = (1.2 +/- 0.2) x 10(-3) M and (6.2 +/- 0.7) x 10(-5) M, respectively) were determined. The increase of koff values reflects the stabilization of the basic form of HSA-heme-Fe by ligands (e.g., abacavir and warfarin) that bind to Sudlow's site I. This event parallels the stabilization of the six-coordinate derivative of the HSA-heme-Fe(II)-NO atom. Present data highlight the allosteric modulation of HSA heme-Fe(II) reactivity by heterotropic effectors. (c) 2008 Elsevier Inc. All rights reserved
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