Molecular basis for enhanced activity of posaconazole against Absidia corymbifera and Rhizopus oryzae.
Posaconazole and itraconazole were more potent inhibitors of ergosterol synthesis, in both intact cells and cell extracts from Absidia corymbifera and Rhizopus oryzae, than voriconazole and fluconazole. Similarly, expression of CYP51 from R. oryzae in Saccharomyces cerevisiae significantly increased resistance to fluconazole and voriconazole but not to posaconazole and itraconazole.
Chau
Andrew S
AS
Schering-Plough Research Institute, 2015 Galloping Hill Road, 4700, Kenilworth, NJ 07033, USA.
Chen
Guodong
G
McNicholas
Paul M
PM
Mann
Paul A
PA
D020095:Absidia / Q000187:drug effects*; D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D004875:Ergosterol / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D012233:Rhizopus / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D058886:Sterol 14-Demethylase; D014230:Triazoles / Q000494:pharmacology*
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase; D004875:Ergosterol