Fluconazole upregulates sconC expression and inhibits sulphur metabolism in Microsporum canis.
Azole derivatives such as fluconazole are the mainstay of therapeutic agents for the treatment of fungal infections. Their mode of action involving alteration in the conversion of lanosterol to ergosterol is well established. Here we report the effect of fluconazole on the sulphur metabolism negative regulator gene (sconC) in Microsporum canis. Characterization of the M. canis sconC gene revealed that its ORF is comprised of 495bp interrupted by four introns of 47-70bp. Exposure of M. canis in suspension to fluconazole upregulates sconC mRNA level and protein expression as determined by Northern and Western blot analysis, respectively. Upregulation of sconC was accompanied by inhibition of sulphur metabolism of the fungus resulting in a greatly reduced incorporation of radioactive labelled sulphuric acid into fungal proteins. These data establish that in addition to its action on ergosterol synthesis, fluconazole acts on other biological pathways in fungal cells.
Uthman
Aumaid
A
Ludwig Boltzmann Institute for Studies of Venero-Dermatological Infectious Diseases, Medical University of Vienna, Vienna, Austria.
Dockal
Michael
M
Söltz-Szöts
Josef
J
Tschachler
Erwin
E
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005800:Genes, Fungal / Q000235:genetics; D008864:Microsporum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D000935:Antifungal Agents; D005656:Fungal Proteins; D012333:RNA, Messenger; D013455:Sulfur; D015725:Fluconazole