Protection by tetracyclines against ion transport disruption caused by nystatin in human airway epithelial cells.

Polyene antifungal antibiotics like nystatin form monovalent cation pores on the plasma membrane that perturb the intracellular electrolyte milieu, resulting in cell damage. In the present study, we investigated the effects of tetracyclines (minocycline and tetracycline) on ion transporters disrupted by nystatin in cultured human airway Calu-3 cells. Apical application of nystatin (50 microM) on a monolayer of the cells stimulated Na(+)-K(+) pump activity as estimated by ouabain (1 mM)-sensitive short-circuit current (I(sc)). The nystatin-potentiated I(sc) was inhibited by minocycline (IC(50) = 25 microM) or tetracycline (IC(50) = 150 microM) applied only from the apical (nystatin-treated) side. Nystatin increased monolayer conductance that was reversed by the application of tetracyclines. In contrast, ouabain potentiated the nystatin-induced change in the conductance. Further, Na(+)-glucose transport affected by nystatin was also normalized by tetracyclines from the nystatin-treated side of the membrane. These data suggest that tetracyclines may lower the cell permeability potentiated by nystatin, protecting cells against damage.

[The sensitivity of yeasts from the Candida genus isolated from cancer patients to polyene antifungals]. / Sensibilidade de leveduras do gênero Candida, isoladas de pacientes com câncer, a antifúngicos poliênicos.

Candida strains susceptibility from cancer patients were compared with Candida strains susceptibility from patients, without cancer by MIC (minimal inhibitory concentration) and MFC (minimal fungicidal concentration) to Amphotericin B and Nystatin. Broth dilution method and agar dilution method were the procedure employed. The authors find no significant differences between the studied groups. The problem of Candida resistance to polyene antifungals is discussed.

[Characteristics of the final stages of ergosterol biosynthesis in Saccharomyces cerevisiae yeasts]. / Nekotorye osobennosti konechnykh stadii biosinteza érgosterina u drozhzhei Saccharomyces cerevisiae.

A scheme of ergosterol cyclic intermediate transformations in S. cerevisiae has been proposed. It is based on the analysis of sterol composition in strains with mutant blocks of one or two reactions of enzymatic synthesis. Biochemical reactions of modification of cyclic part and side branch of sterol molecule are supposed to be carried out independently.

[Yeast resistance to polyene antibiotics. VII. The interaction of the mutant alleles of the nystatin resistance genes in Saccharomyces cerevisiae]. / Rezistentnost' drozhzhei k polienovym antibiotikam. Soobshchenie VII. Vzaimodeistvie mutantnykh allelei genov nistatinustoichivosti u Saccharomyces cerevisiae.

The data on allele interactions of nystatin resistance genes are presented. It has been shown that the mutant phenotype of heteroallelic hybrids NYS1, NYS4 and, probably, NYS3 is strengthened. The intragenic complementation has been found in NYS2 gene, allowing to imply the multimeric structure of delta 8----delta 7 isomerase which is controlled by this gene.

[Yeast resistance to polyene antibiotics. VI. Isolation and biochemical analysis of strains of Saccharomyces cerevisiae yeasts with mutations in the 2 nystatin-resistance genes]. / Rezistentnost' drozhzhei k polienovym antibiotikam. Soobshchenie VI. Poluchenie i biokhimicheskii analiz shtammov drozhzhei Saccharomyces cerevisiae s mutatsiiami v dvukh genakh nistatinustoichivosti.

The comparative analysis of sterol content in the yeast Saccharomyces cerevisiae strains singly or doubly defective in nystatin resistance genes was carried out. The strains with two mutations in NYS genes were shown to accumulate the sterol mixture, similar to that of the parental singly defective mutant. This type of gene interaction allows to define the main biochemical order of reaction in ergosterol synthesis: methylation in C24 (NYS1), delta 8----delta 7 isomerization (NYS2), C5 (6) and C22 (23) desaturation (NYS3 and NYSX).

[Yeast resistance to polyene antibiotics. IV. A study of the inheritance of changes in the sterol composition of Saccharomyces cerevisiae yeasts caused by mutations of nystatin resistance]. / Rezistentnost' drozhzhei k polienovym antibiotikam. Soobshchenie IV. Izuchenie nasledovaniia izmenenii v sostave sterinov, obuslovlennykh mutatsii ustoichivosti k nistatinu u drozhzhei Saccharomyces cerevisiae.

Sterol content in haploid and diploid strains of yeast having mutations of resistance to nystatin were studied by UV spectrometry method. Heterozygous diploids carrying one or two nystatin resistance mutations have, as a rule, the sterol content of the wild type strains. Segregants of the same genotype demonstrate differences in sterol content. Double mutants nys1 nys2 and nys1 nys3 have UV spectra typical for single nys2 and nys3 mutants, respectively. Double mutants nys1 nysX are characterized by a "mixed" UV spectra of sterols.

[Characteristics of the range of mutations in nystatin resistance induced in yeasts by 6-N-hydroxylaminopurine]. / Osobennosti spektra mutatsii nistatinustoichivosti, indutsirovannykh u drozhzhei 6-N-gidroksilaminopurinom.

A simple procedure for induction of nistatin-resistant mutants in yeasts under the action of 6-N-hydroxylaminopurine (HAP) is proposed. Some differences between the spectra of mutations induced by HAP and UV-light are observed: HAP induces dominant and double recessive mutants more frequently.

[Yeast resistance to polyene antibiotics. II. An analysis of the sterol composition of Saccharomyces cerevisiae yeasts resistant to nystatin]. / Rezistentnost' drozhzhei k polienovym antibiotikam. Soobshchenie II. Analiz sostava sterinov u drozhzhei Saccharomyces cerevisiae, ustoichivykh k nistatinu.

The recessive yeast mutations nys providing resistance to polyene antibiotics in Saccharomyces cerevisiae are described. The analysis of UV-absorbtion spectra of sterols from cells of different mutants allows to assume that NYS genes control synthesis of ergosterol. The lack of alterations in the sterol composition of the same strains carrying dominant nystatin resistance mutations points to the existence of another mechanisms of resistance to polyene antibiotics, in addition to the sterol mechanism.

[Yeast resistance to polyene antibiotics. III. Phenotypic analysis of polyene-resistant sterol mutants of Saccharomyces cerevisiae yeasts]. / Rezistentnost' drozhzhei k polienovym antibiotikam. Soobshchenie III. Femotipicheskii analiz polienrezistentnykh sterinovykh mutantov drozhzhei Saccharomyces cerevisiae.

The pleiotropic effects of nystatin resistant mutations have been studied. It has been shown that resistance to nystatin is often accompanied by temperature-sensitivity and, in some cases, by osmotic remedial sensitivity. The dependence of the expression of the mutations on temperature is demonstrated. A new type of conditional nystatin-dependent mutants is found. All nys2 mutants have a defected membrane and are stained on a methylene blue containing media. At the same time, the mutations under investigation do not affect the respiratory competence and the exoenzyme activity of acid phosphatases.

[Metabolic characteristics of a nystatin-resistant strain of a fungal producer of fusidic acid]. / Osobennosti metabolizma nistatinorezistentnogo shtamma griba-produtsenta fuzidievoi kisloty.

The physiological and morphofunctional properties of the polyene-sensitive and resistant mutants of fungus producing fusidic acid were studied comparatively. The highly active nystatin resistant mutant was characterized by the decreased growth rates, lowered sporulation levels, retarded synthesis of nucleic acids and protein, lower respiration activity and higher mycelium lipid contents. The ultrastructural investigation of the polyene-resistant strain revealed the presence of lower numbers of ribosomes, membrane structures and mitochondria. Destructive changes in mitochondria and lipid masses in the hyphal cytoplasm were also observed.