Antibiotic Yc 73 of Pseudomonas Origin. I

Egawa, Yoshiyuki; Umino, Kimio; Awataguchi, Shigemi; Kawano, Yoshishige; Okuda, Tomoharu

doi:10.7164/antibiotics.23.267

Cited by 25 publications

(11 citation statements)

References 7 publications

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“…The F3d fraction, produced by P. aeruginosa LV strain, demonstrated activity against N315, BEC9393, ATCC 10031, and Kpn -KPC 19 strains (Cardozo et al, 2013; Kerbauy et al, 2016), with the metalloantibiotic compound Fluopsin C being the major component with strong antibiotic activity (de Oliveira et al, 2016). Elementary analysis, mass spectrometry, chemical proprieties and biological activity evaluation proved that P. aeruginosa LV strain-metalloantibiotic is identical to Fluopsin C (YC 73), a compound described in earlier studies (Egawa et al, 1970, 1971; Itoh et al, 1970; Otsuka et al, 1972; Ma et al, 2013; de Oliveira et al, 2016).…”

Section: Discussionmentioning

confidence: 63%

Fluopsin C for Treating Multidrug-Resistant Infections: In vitro Activity Against Clinically Important Strains and in vivo Efficacy Against Carbapenemase-Producing Klebsiella pneumoniae

et al. 2019

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The increasing emergence of multidrug-resistant (MDR) organisms in hospital infections is causing a global public health crisis. The development of drugs with effective antibiotic action against such agents is of the highest priority. In the present study, the action of Fluopsin C against MDR clinical isolates was evaluated under in vitro and in vivo conditions. Fluopsin C was produced in cell suspension culture of Pseudomonas aeruginosa LV strain, purified by liquid adsorption chromatography and identified by mass spectrometric analysis. Bioactivity, bacterial resistance development risk against clinically important pathogenic strains and toxicity in mammalian cell were initially determined by in vitro models. In vivo toxicity was evaluated in Tenebrio molitor larvae and mice. The therapeutic efficacy of intravenous Fluopsin C administration was evaluated in a murine model of Klebsiella pneumoniae (KPC) acute sepsis, using six different treatments. The in vitro results indicated MIC and MBC below 2 μg/mL and low bacterial resistance development frequency. Electron microscopy showed that Fluopsin C may have altered the exopolysaccharide matrix and caused disruption of the cell wall of MDR bacteria. Best therapeutic results were achieved in mice treated with a single dose of 2 mg/kg and in mice treated with two doses of 1 mg/kg, 8 h apart. Furthermore, acute and chronic histopathological studies demonstrated absent nephrotoxicity and moderate hepatotoxicity. The results demonstrated the efficacy of Fluopsin C against MDR organisms in in vitro and in vivo models, and hence it can be a novel therapeutic agent for the control of severe MDR infections.

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Section: Discussionmentioning

confidence: 63%

Fluopsin C for Treating Multidrug-Resistant Infections: In vitro Activity Against Clinically Important Strains and in vivo Efficacy Against Carbapenemase-Producing Klebsiella pneumoniae

et al. 2019

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“…Our discovery of the fluopsin C biosynthetic pathway further expands the functions of metalbinding natural products beyond metal acquisition. As we and others have shown, fluopsin C exhibits broad-spectrum antibiotic activity against microbes and potent cytotoxicity against mammalian cells and whole animals, and it is much less active against various P. aeruginosa strains (24,26,29). Because fluopsin C contains copper, its antimicrobial mechanism likely differs from existing antibiotic classes or the copper-binding compound xanthocillin, which exhibits diminished antimicrobial effect in the presence of copper (10).…”

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confidence: 83%

“…We also found that fluopsin C is effective against multidrug-resistant strains of Acinetobacter baumannii and Staphylococcus aureus (table S1). By contrast, P. aeruginosa strains are much more resistant to fluopsin C than any other bacterial or fungal strains that were tested (24,26,28). For example, P. aeruginosa PAO1, the fluopsin C producer, can resist >70 mg/ml of fluopsin C (table S1).…”

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confidence: 98%

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Biosynthesis of fluopsin C, a copper-containing antibiotic from Pseudomonas aeruginosa

Patteson

Putz

Tao

et al. 2021

Science

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A copper-containing antibiotic Bacteria require transition metal ions for biological processes and must also protect themselves against excess metal, which is toxic. Patteson et al . explored how the environmental bacterium Pseudomonas aeruginosa uses a five-enzyme pathway to synthesize a small-molecule complex, fluopsin C, which is built from cysteine and contains a copper ion. The biosynthesis involves unusual enzymatic transformations that convert cysteine to a thiohydroximate, two of which chelate a copper ion in the final natural product. Fluopsin C protects P. aeruginosa from excess copper and also acts as a broad-spectrum antibiotic against other bacteria. —VV

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“…and other platinum anticancer drugs.12 Induction of MT biosynthesis may be useful in mediating the dose-limiting renal toxicity of these agents, 13 but conversely, such increased in vivo platinum(ll) binding to MT may make tumor cells more resistant to the anticancer effects of platinum drugs.14"16 We have reported mixed-metal adducts from the reactions of platinum(II) with Cd7MT and native MT and the reconstitution of apoMT with platinum(II) to produce Pt7MT.17 Stoichiometries of metal binding under aerobic and anaerobic conditions were presented, and the reactivity of the Pt7MT adduct toward electrophiles indicated a significant kinetic inhibition of cysteine modification in comparison to reactions with apoMT, Cd7MT, and Zn7MT. The Pt7MT adduct is formed at pH ~7 even in the presence of a large excess of platinum(II), and we suggested that this stable seven-metal adduct has Pt-cys clusters and thát the single methionine of MT is also involved in platinum(II) binding.…”

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confidence: 99%