title: Synergistic action of nikkomycin X/Z with azole antifungals on Candida albicans.
abstract: Fluconazole, ketoconazole and tioconazole were shown to act synergistically in vitro with the antibiotic nikkomycin X/Z on the pathogenic fungus Candida albicans. The phenomenon was demonstrated using a checkerboard technique and growth inhibition experiments. The azole antifungal agents, even at concentrations not affecting growth, decreased the incorporation of the 14C-label from [14C]glucose into chitin of the candidal cell wall. After 3 h incubation with tioconazole, 1 microgram ml-1, the incorporation of the radiolabelled glucose into chitin of intact cells and regenerating spheroplasts of C. albicans was inhibited by 43% and 30%, respectively. Moreover, the relative chitin content was approximately 45% lower than that of control cells. The chitin content increased after prolonged incubation with azoles, thus confirming the known phenomenon of azole-induced uncoordinated chitin synthesis and deposition. On the other hand, azole derivatives had very little effect on the rate of nikkomycin transport into C. albicans cells. A sequential blockade mechanism of synergism is proposed.
authors.affiliation: Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Milewski
authors.forename: F
authors.initials: F
authors.lastname: Mignini
authors.forename: E
authors.initials: E
authors.lastname: Borowski
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001692:Biological Transport; D002176:Candida albicans / Q000187:drug effects*; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D007700:Kinetics; D011134:Polysaccharides / Q000096:biosynthesis
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001393:Azoles; D007093:Imidazoles; D011134:Polysaccharides; D015725:Fluconazole; C011952:nikkomycin; D005947:Glucose; D007654:Ketoconazole; C020527:tioconazole