A Critical Review of the Properties of Fusidic Acid and Analytical Methods for Its Determination.

Fusidic acid, an antibiotic produced from the Fusidium coccineum fungus, belongs to the class of steroids, but has no corticosteroid effects. It is indicated for the treatment of infections caused by methicillin-resistant Staphylococcus aureus strains. The aim of this study was to search for the properties of fusidic acid published so far in the literature, as well as the methods developed for its determination in biological samples and pharmaceutical formulations. From the findings, we can conclude that fusidic acid has been used for decades and is indicated for the treatment of serious infections caused by Gram-positive microorganisms to this day. Furthermore, it is a hypoallergenic agent, has low toxicity, shows low resistance, and has no cross-resistance with other clinically used antibiotics. The analytical method of high-performance liquid chromatography has been widely used for determining fusidic acid, since it can reduce the cost and time of analysis, making it more viable for routine quality control in the pharmaceutical industry.

Biotransformation of clovane derivatives. Whole cell fungi mediated domino synthesis of rumphellclovane A.

Here we describe the biotransformation of clovane derivatives by filamentary fungi Pestalotiopsis palustris and Penicillium minioluteum, and the application of the latter to the synthesis and determination of the absolute configuration of rumphellclovane A (2). Methoxyclovanol (1), a growth inhibitor of the phytopathogen Botrytis cinerea, is metabolised by P. palustris to yield rumphellclovane A (2), a natural compound recently isolated from the gorgonian coral Rumphella antipathies, two new compounds, (1R,2S,5S,8R,9S,10R)-2-methoxyclovane-9,10-diol (5) and (1S,2S,5S,7R,8R,9R)-2-methoxyclovane-7,9-diol (6), hydroxylated in positions not easily accessed by classic synthetic chemistry, and clovanodiols 3 and 4. P. minioluteum is able to selectively transform methoxyclovanol (1) into clovanodiols 3 and 4 and, in turn, lactone 8, the putative intermediate in the above mentioned synthesis of rumphellclovane A (2), into compound 2 via a domino process. The ability of P. minioluteum to carry out the cleavage of ethers on clovane derivatives is also evaluated.

Three highly oxygenated caryophyllene sesquiterpenes from Pestalotiopsis sp., a fungus isolated from bark of Pinus taeda.

A Pestalotiopis sp. was isolated from the trunk bark of Pinus taeda. The fungus was cultivated in liquid medium and produced three highly oxygenated caryophyllene sequiterpene derivatives, named pestalotiopsolide A, taedolidol and 6-epitaedolidol, respectively. The sesquiterpenes were isolated by silica gel based chromatographic procedures and their structures were elucidated by NMR spectroscopic data.

Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge.

The isolation and structure determination of a new chlorinated benzophenone antibiotic, pestalone (1), is described. The new compound was produced by a cultured marine fungus only when a unicellular marine bacterium, strain CNJ-328, was co-cultured in the fungal fermentation. The fungus, isolated from the surface of the brown alga Rosenvingea sp. collected in the Bahamas Islands, was identified as an undescribed member of the genus Pestalotia. The structure of 1, initially assigned with only modest confidence by combined spectral and chemical data, was confirmed by single-crystal X-ray analysis. Pestalone (1) exhibits moderate in vitro cytotoxicity in the National Cancer Institute's 60 human tumor cell line screen (mean GI(50) = 6.0 microM). More importantly, pestalone shows potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium (MIC = 78 ng/mL), indicating that pestalone should be evaluated in advanced models of infectious disease.

Isolation and partial characterization of an adhesin from Fonsecaea pedrosoi.

We showed previously that mannose and N-acetylglucosamine (GlcNAc) residues are involved in the process of adhesion of Fonsecaea pedrosoi, the causative agent of chromoblastomycosis, to epithelial cells. It was then suggested that lectin-like molecules would be involved in the interaction. In the present study, we used fluorescein isothiocyanate-labeled neoglycoproteins (bovine serum albumin [BSA]-mannose and BSA-GlcNAc) to analyze the presence of sugar-binding proteins on the surface of conidia of F. pedrosoi grown at 28 and 37 degrees C. Binding of the neoglycoproteins was measured using flow cytometry. Fungal conidia expressed high levels of binding sites for BSA-mannose and BSA-GlcNAc when grown at 37 degrees C rather than 28 degrees C. Binding was inhibited by previous incubation of the conidia in the presence of chloroquine and trypsin. Chloroquine treatment also inhibited the interaction of fungal conidia with Chinese hamster ovary cells. Extracts from the conidia, obtained using a mechanical cell homogenizer, were purified by affinity chromatography using mannose-agarose or GlcNAc-agarose column. Polyacrylamide gel electrophoresis of the purified material from both columns showed a single protein band of 50 kDa, suggesting that the same lectin-like protein recognizes both carbohydrates.

Seimatoantlerium tepuiense gen. nov., a unique epiphytic fungus producing taxol from the Venezuelan Guyana.

Seimatoantlerium gen. nov., type species, S. tepuiense sp. nov. is proposed for an acervular fungus producing 4-septate, holoblastic conidia with 6-8 unbranched, apical appendages that dehisce as an appendage apparatus and also commonly possessing one or two exogenous basal appendages as well as a pedicel. It is compared with Seimatosporium, Seimatosporiopsis, and other genera. It is epiphytic on Maguireothamnus speciosus, a rubiaceous plant endemic to the tepuis of southeastern Venezuela. It produces the anti-oomycetous anticancer compound, taxol, as shown by immunological and spectroscopic methods. Taxol production is discussed relative to the ability of this fungus to exist in an extremely moist ecosystem, as well as to its relationship to other plant associated fungi.

Seimatoantlerium tepuiense gen. nov., a unique epiphytic fungus promoting taxol from the Venezuelan Guyana

Seimatoantlerium gen. nov., type species, S.tepuiense sp. nov. is proposed for an acervular fungus producing 4-septate, holobastic conidia with 6-8 unbranched, apical appendages that dehisce as an appendage apparatus and also commonly possessing one or two exogenous basal appendages as well as a pedicel. It is compared with Seimatosporium, Seimatosporiopsis, and other genera. It is epiphytic on Maguireothamnus speciosus, a rubiaceous plant endemic to the tepuis of southeastern Venezuela. It produces the anti-oomycetous anticancer compound, taxol, as shown by immunological and spectroscopic methods. Taxol production is discussed relative to the ability of this fungus to exist in an extremely moist ecosystem, as well as to its relationship to other plant associated fungi. (AU)

Carbohydrate and lipid components of hyphae and conidia of human pathogen Fonsecaea pedrosoi.

The carbohydrate and lipid components of mycelium and conidia of Fonsecaea pedrosoi (Brumpt) were analysed by paper, thin-layer and gas-chromatography, mass spectrometry and ultraviolet spectroscopy. Glucose, mannose, galactofuranose, rhamnose and glucosamine were polysaccharide components identified in F. pedrosoi. Significant changes in the carbohydrate pattern occurred during the conversion of mycelium into conidia. Rhamnose was predominant in conidia whereas galactose was prominent in mycelium. Palmitic, stearic, oleic, linoleic, and arachidonic acids were the fatty acids identified in the total lipid fraction. Palmitic and oleic acids were major fatty acids. Marked alterations in the fatty acid constituents were observed between the cell types of F. pedrosoi. Arachidonic acid was detected only in conidia and linoleic acid was preferentially identified in mycelium. Differences in the sterol composition was also associated with morphogenesis in F. pedrosoi. Two main sterols, ergosterol and another less polar sterol, not fully characterized, were found in mycelium whereas in conidia only the latter sterol was present.

Fonsecaea pedrosoi: lipid composition and determination of susceptibility to amphotericin B.

Conidia and mycelial cells of Fonsecaea pedrosoi ATCC 46428 were obtained for analyses of lipid composition. Total lipids, phospholipids, sterols, and qualitative sterols and fatty acid composition were determined. A higher lipid content was detected in conidia than in mycelial cells of Fonsecaea pedrosoi, which could not be attributed to total sterols and phospholipids. In both forms of this fungus, ergosterol was the only sterol detected. The minimal inhibitory concentration of amphotericin B was lower for conidia than for mycelium.