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Open AccessJournal ArticleDOI

Rapamycin (ay-22, 989), a new antifungal antibiotic i. taxonomy of the producing streptomycete and isolation of the active principle

Claude Vezina, +2 more
- 01 Oct 1975 - 
- Vol. 28, Iss: 10, pp 721-726
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TLDR
From its characteristic ultraviolet absorption spectrum rapamycin can be classified as a triene and its activity is compared with that of amphotericin B, candicidin and nystatin.
Abstract
A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum. The antibiotic-producing microorganism was characterized and identified as Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 mug/ml. Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.

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Exogenous shikimic acid stimulates rapamycin biosynthesis in Streptomyces hygroscopicus.

TL;DR: A chemically defined medium was developed which satisfies the nutritional needs of the Streptomyces hygroscopicus strain producing the immunosuppressant rapamycin and the previously observed inhibition of the synthesis by phenylalanine was not reversed by shikimate.
Journal ArticleDOI

Antifungal combinations in Mucorales: A microbiological perspective.

TL;DR: In patients with ketoacidosis and rhino‐orbito‐cerebral infection, combination of polyene with caspofungin was effective, and despite promising experimental data, adjunctive therapy with the iron chelator deferasirox was unfavourable and was associated with a higher mortality than monotherapy with liposomal amphotericin B.
Journal ArticleDOI

Comparative metabolic profiling reveals the key role of amino acids metabolism in the rapamycin overproduction by Streptomyces hygroscopicus

TL;DR: Comparative metabolic profiling between the wild-type and mutant strain showed that amino acids metabolism played an important role in the synthesis of rapamycin, especially lysine, valine, tryptophan, isoleucine, glutamate, arginine and ornithine, and real-time PCR and enzyme activity assays demonstrated that dihydrodipicolinate synthase involved withLysine metabolism played vital role inThe biosynthesis of rap amycin.
Journal ArticleDOI

Improved mitochondrial stress response in long-lived Snell dwarf mice.

TL;DR: It is reported that Snell dwarf mice, which show 30%–40% lifespan extension and prolonged healthspan, exhibit augmented mitochondrial stress responses, and provides a rationale for future mouse lifespan studies involving compounds that induce mtUPR.
References
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Journal Article

Protein Measurement with the Folin Phenol Reagent

TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
Journal ArticleDOI

Methods for characterization of Streptomyces species

TL;DR: The methods used by collaborators in the ISP for emendation of descriptions of type and neotype strains of the genus Streptomyces (Actinomycetales) are presented.
Journal ArticleDOI

Simplified, Accurate Method for Antibiotic Assay of Clinical Specimens

TL;DR: Serum specimens are tested directly rather than diluting them to a narrow range of antibiotic concentrations, possible because of a procedure for calculations that recognizes the curvilinear relationship between zone sizes and antibiotic concentrations.
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