白念珠菌胞内铁离子通过Hap43-Pck1调控生物被膜和耐药性形成的分子机制研究

皮肤粘膜念珠菌病是皮肤科的常见病，其中白念珠菌是主要致病菌，可侵入人体组织引起死亡率高达40%的侵袭性念珠菌病。白念珠菌生物膜是白念珠菌侵袭宿主和产生耐药性的重要原因之一，但关于白念珠菌生物膜和耐药性形成的分子机制尚不明确。我们前期通过基因敲除，Real-time PCR等方法，发现在富铁环境下，HAP43基因可能通过上调PCK1基因表达调控白念珠菌浮游状态耐药性形成。在此基础上，我们拟开展白念珠菌胞内铁离子通过Hap43-Pck1调控生物膜和生物膜耐药性形成的分子机制研究。以白念珠菌HAP43和PCK1基因缺失菌为工具菌，通过蛋白质谱分析、白念珠菌-巨噬细胞相互作用等方法深入探讨在不同铁浓度下，HAP43和PCK1基因是否促进白念珠菌生物膜及生物膜耐药性的形成。阐明白念珠菌HAP43和PCK1基因调控生物膜和生物膜耐药性形成的分子机制，为白念珠菌生物膜和生物膜耐药性形成的防治提供新思路。

Candidiasis of the skin and mucous membranes is a common disease in dermatology. Candida albicans is the main pathogenic fungi, which can invade human tissues and cause invasive candidiasis with a mortality rate of up to 40%. C.albicans biofilm is one of the important reasons for C.albicans to invade the host and develop drug resistance, but the molecular mechanism of C.albicans biofilm and biofilm resistance formation is not yet clear. Our previous studies through gene knockout, Real-time PCR and other methods found that in an iron-replete environment, HAP43 gene may regulate planktonic C.albicans resistance formation by up-regulating the expression of PCK1 gene. On this basis, we intend to study the molecular mechanism by which intracellular iron ions in C.albicans regulate the biofilm and biofilm resistance formation through hap43-pck1. Using C.albicans HAP43 and PCK1 genes deletion fungi as tool fungi, we deeply study whether HAP43 and PCK1 genes promote C.albicans biofilm and biofilm resistance formation under different iron concentrations by protein mass spectrometry analysis and C.albicans macrophage interaction. Elucidate the molecular mechanism of C.albicans HAP43 and PCK1 genes regulating biofilm and biofilm resistance formation, and provide new ideas for the prevention and treatment of C.albicans biofilm and biofilm resistance formation.