Research for antifungal mechanisms and therapeutics in refractory deep mycoses

白色念珠菌是最重要的条件致病菌之一，其细胞膜所含的甾醇类在人体致病过程中起着重要作用。在这里，我们创建了白色念珠菌erg3零突变体来描述由缺陷的δ - 5,6 -去饱和酶引起的固醇代谢失调对唑抗真菌敏感性、致病性和形态发生的影响。erg3/erg3菌株表现出高度的唑抗性，麦角糖- 7,22 -二烯-3β-醇的积累不受氟康唑暴露的影响。然而，由δ - 5,6 -去饱和酶缺陷引起的固醇代谢失调增加了对十二烷基硫酸钠（SDS）的易感性，降低了系统性念珠菌病小鼠模型的毒力，并抑制了固体培养基和液体培养基中丝状菌的生长。我们的结果有助于进一步了解形态发生的多种信号通路的联系。

We Sterols constituting cell membrane of Candida albicans, one of the most important opportunistic pathogen, play some important roles in causing disease in humans. Here, we created the C. albicans erg3 null mutant to describe effects of sterol dysbolism by defective delta-5, 6-desaturase on azole antifungal susceptibilities, pathogenicity and morphogenesis. The erg3/erg3 strain showed highly azole resistance and ergosta-7, 22-dien-3β-ol accumulated in place of ergosterol was not affected by fluconazole exposure. While, sterol dysbolism by defective delta-5, 6-desaturase increased vulnerability to Sodium dodecyl sulfate (SDS), reduced virulence in a mouse model of systemic candidiasis and suppressed filamentous growth on solid medium and in liquid culture without shaking. Our results are useful for further under standing linkage of multiple signaling pathways for morphogenesis.