ERG3 Disruption in Candida albicans Resulted in Highly Azole Resistant but Less Virulent in Murine Candidiasis.

T. MIYAZAKI, Y. MIYAZAKI, H. KAKEYA, K. YANAGIHARA, Y. HIRAKATA, K. TOMONO, T. TASHIRO, S. KOHNO

Abstract: 

Background: Delta-5,6-desaturase is an enzyme of ergosterol biosynthesis pathway and encoded by ERG3 gene. We previously deleted ERG3 in Candida albicans and reported that the MIC of erg3 null mutant to fluconazole was over 1024 mcg/ml (41st ICAAC). Disruption of this gene resulted in azole resistance, however, effect on pathogenesis was unknown. We tested sensitivity against various chemical stresses for an erg3 null mutant, and virulence in murine Candidiasis. Methods: C. albicans CAD1U strain (erg3 ::hisG-URA3-hisG/ERG3) and CAE3DU (erg3 ::hisG-URA3-hisG/erg3 ::hisG) strain were made from the CAI4 strain (ura3/ura3, ERG3/ERG3). Each strain was tested its in vitro susceptibilities against acid stress at pH 2 - 9, and against heat stress at 16, 30, or 37 °C. Cells were exposed to each specific stress and viable cell counts wew measured. In vivo virulence was tested in female BALB/c mice, 8 weeks old, with intravenous inoculation of 1×106 yeast cells/mouse. Survival and fngal burden in kidney were analyzed. Results: In vitro study: Vialble cell counts of CAE3DU strain, an erg3 disruptant, at pH 2 was significantly less than those of CAD1U or CAI4. Growth rate of CAE3DU was the same level at 30 or 37°C as those of CAD1U or CAI4, but significantly lower at 16 °C. In vivo study: Survival rate of mice infected with CAE3DU was 90% at day 21, while all mice infected with CAD1U died by day 10. (p
2002

abstract No: 

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Full conference title: 

42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd