title: A broad-spectrum antifungal from the marine sponge Hyrtios erecta.
abstract: Spongistatin 1, a macrocyclic lactone polyether from the marine sponge Hyrtios erecta, was fungicidal for a variety of opportunistic yeasts and filamentous fungi, including strains resistant to amphotericin B, ketoconazole and flucytosine. In broth macrodilution assays, MICs ranged from 0.195 to 12.5 microg/ml, and minimum fungicidal concentrations ranged from 3.12 to 25 microg/ml. Initial disk diffusion screens with six related macrocyclic lactone polyethers from H. erecta and Spirastrella spinispirulifera, revealed that these polyethers were also antifungal. The fungicidal activity of spongistatin 1 was confirmed in killing kinetics studies, where killing of Candida albicans and Cryptococcus neoformans occurred within 6 and 12 h, respectively. During the killing kinetics experiments, non-treated C. albicans maintained the yeast morphology. However, elongated forms resembling germ tubes were the predominant morphologic form in spongistatin 1-treated C. albicans cultures. The spongistatins show promise as potential antifungal agents and as probes to study fungal morphogenesis and nuclear division.
authors.affiliation: Department of Microbiology, Cancer Research Institute, Arizona State University, Tempe 85287-1604, USA. pettitr@asu.edu
authors.forename: R K
authors.initials: RK
authors.lastname: Pettit
authors.forename: S C
authors.initials: SC
authors.lastname: McAllister
authors.forename: G R
authors.initials: GR
authors.lastname: Pettit
authors.forename: C L
authors.initials: CL
authors.lastname: Herald
authors.forename: J M
authors.initials: JM
authors.lastname: Johnson
authors.forename: Z A
authors.initials: ZA
authors.lastname: Cichacz
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development; D004352:Drug Resistance, Microbial; D004988:Ethers, Cyclic / Q000302:isolation & purification / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects*; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D011161:Porifera / Q000737:chemistry*; D000095702:Polyether Toxins
chemical_list: D000935:Antifungal Agents; D004988:Ethers, Cyclic; D007783:Lactones; D018942:Macrolides; C083856:spongistatin 1; D000095702:Polyether Toxins