1,721,043 research outputs found
Molecular and sub-cellular topology of the enzyme L-ornithine N-oxygenase (PvdA) in Pseudomonas aeruginosa
No full textDa inserir
An essential transcriptional regulator: The case of Pseudomonas aeruginosa fur
No full textCommentary article on the essential role of the iron uptake transcriptional regulator Fur in the human pathogen Pseudomonas aeruginos
The antimetabolite 3-bromopyruvate selectively inhibits Staphylococcus aureus
Full text linkThe rise in antibacterial resistance jeopardizes current therapeutic strategies to control infections, soliciting the development of novel antibacterial drugs with new mechanisms of action. In this work we report the discovery of a potent and selective anti-staphylococcal activity of 3-bromopyruvate (3BP), an antimetabolite in preclinical development phase as an anticancer drug. 3BP showed bactericidal activity against Staphylococcus aureus, with active concentrations comparable to those reported to be effective against cancer cells. In contrast, no relevant activity was observed against other ESKAPE bacteria (Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). The anti-staphylococcal activity of 3BP was confirmed using a panel of human and veterinary strains, including multidrug-resistant isolates. 3BP showed highest antibacterial activity under conditions which increase 3BP stability (acidic pH) or promote S. aureus fermentative metabolism (anaerobiosis), although 3BP was also able to kill metabolically-inactive cells. 3BP showed synergism with gentamicin, and also disrupted preformed S. aureus biofilms, at concentrations only slightly higher than those inhibiting planktonic cells. This study unravels novel antibacterial and anti-biofilm activities for the anticancer drug 3BP, thus paving the way for further pre-clinical studies
Aminoarabinosylation of lipid A is critical for the development of colistin resistance in Pseudomonas aeruginosa
Full text linkLipid A aminoarabinosylation is invariably associated with colistin resistance inPseudomonas aeruginosa; however, the existence of alternative, aminoarabinosylation-independent colistin resistance mechanisms in this bacterium remained elusive. By combining reverse genetics with experimental evolution assays we demonstrate that a functional lipid A aminoarabinosylation pathway is critical for acquisition of colistin resistance in reference and clinicalP. aeruginosaisolates. This highlights lipid A aminoarabinosylation as a promising target for the design of colistin adjuvants againstP. aeruginosa
5-FLUOROCITOSINA COME AGENTE ANTIBATTERICO
No full textLa presente invenzione concerne il farmaco antimicotico 5-fluorocitosina (anche detta
10 flucitosina ed abbreviata 5-FC) e la sua potente attività come antibatterico, in particolare la
sua attività anti-virulenza nei confronti di Pseudomonas aeruginos
Biosensor for N-3-oxo-dodecanoyl-homoserin lactone detection
No full textLa presente invenzione concerne la costruzione di un biosensore per la rilevazione di
3OC12-HSL, il principale segnale di quorum sensing (QS) prodotto da Pseudomonas
aeruginosa, in campioni di laboratorio ed in campioni clinici, e per lo screening di inibitori
del sistema 3OC12-HSL-dipendente di Pseudomonas aeruginosa
Pyoverdine and proteases affect the response of pseudomonas aeruginosa to gallium in human serum
Full text linkGallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3 )3 ] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections
5-fluorocitosina come agente antibatterico.
No full textLa presente invenzione concerne il farmaco antimicotico 5-fluorocitosina (anche detta
10 flucitosina ed abbreviata 5-FC) e la sua potente attività come antibatterico, in particolare la
sua attività anti-virulenza nei confronti di Pseudomonas aeruginos
Subcellular 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(NO3)(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 mu M and from 4 to 64 mu M, respectively. Ga(NO3)(3) delayed the entry of A. baumannii into the exponential phase and drastically reduced bacterial growth rates. Ga(NO3)(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(NO3)(3) also protected Galleria mellonella larvae from lethal A. baumannii infection, with survival rates of >= 75%. At therapeutic concentrations for humans (28 mu M plasma levels), Ga(NO3)(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(NO3)(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
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