title: UK-2A, B, C, and D, novel antifungal antibiotics from Streptomyces sp. 517-02 VII. Membrane injury induced by C9-UK-2A, a derivative of UK-2A, in Rhodotorula mucilaginosa IFO 0001.
abstract: UK-2A is a potent antifungal antibiotic and its structure is highly similar to that of antimycin A3 (AA). UK-2A and AA inhibit mitochondrial electron transport at complex III. However, the antifungal activities of UK-2A and AA disappear after 48-hour treatment. In an attempt to improve the duration of the antifungal activity of UK-2A, several UK-2A derivatives were prepared by substituting its nine-membered dilactone ring with an n-alkyl or an isoprenyl moiety. Among all the derivatives tested, C9- and C10-UK-2A showed the most potent and durable antifungal activities against a strict aerobic yeast, Rhodotorula mucilaginosa IFO 0001. C9-UK-2A, in particular, continued to demonstrate its broad-spectrum antifungal activity after 120-hour treatment. Therefore, we focused on C9-UK-2A to further examine its mode of action against the yeast. Interestingly, C9-UK-2A did not inhibit cellular respiration of the cells even at concentrations greater than 100 microg/ml. C9-UK-2A gradually induced the efflux of potassium ions from the cells. Moreover, C9-UK-2A gradually induced the release of glucose from glucose-encapsulating liposomes. The patterns of efflux and release induced by C9-UK-2A were not as rapid as those seen with amphotericin B. These results suggest a membrane injury caused by C9-UK-2A in R. mucilaginosa IFO 0001.
authors.affiliation: Graduate School of Science, Osaka City University, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tani
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Usuki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Motoba
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Makoto
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D000968:Antimycin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008081:Liposomes / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010101:Oxygen Consumption; D011188:Potassium / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D012248:Rhodotorula / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000935:Antifungal Agents; C456044:C10-UK-2A antibiotic; C456043:C9-UK-2A antibiotic; D007783:Lactones; D008081:Liposomes; D011725:Pyridines; C101439:UK 2A; D000968:Antimycin A; C004510:blastmycin; D005947:Glucose; D011188:Potassium