烟曲霉细胞壁及其GPI锚定结构研究进展

对烟曲霉而言,细胞壁不仅作为其坚硬的外骨骼保证了结构的完整性,对细胞进行保护,而且介导了真菌内部生理状态与外界环境之间的交流。由于缺乏精确快速的诊断方法且抗曲霉感染药物疗效不佳,以及烟曲霉菌株对新药耐受的不断增强,导致真菌感染的死亡率非常高。近年来,以细胞壁为药物靶点的研究越来越多。本文综述了烟曲霉细胞壁的研究进展以及与细胞壁密切相关的GPI锚定结构的研究现状,揭示了抗真菌新药的研制任重道远,迫切需要研究宿主菌的毒力分子机制,寻找更好的药物靶点。

桂皮醛抗曲霉的敏感性及对烟曲霉细胞壁的影响

目的探讨桂皮醛对曲霉的抗菌活性及对烟曲霉细胞壁的影响,为研发新型靶向抗真菌药物提供依据。方法用沙氏琼脂(4%葡萄糖、1%蛋白胨、2%琼脂)试管稀释法测定曲霉菌MIC。将烟曲霉菌分别制备成1×106 CFU/mL的0.1%的桂皮醛及卡泊芬净吐温80沙氏(4%葡萄糖、1%蛋白胨)液基,37℃孵育48h后,离心、制片,透射电镜观察,以氟康唑作对照。结果桂皮醛、卡泊芬净、氟康唑对曲霉菌MIC(烟曲霉菌0.019 5μg/mL、0.039 1μg/mL、>32μg/mL,黄曲霉菌0.039 1μg/mL、0.039 1μg/mL、>32μg/mL)。电镜显示0.1%的桂皮醛及卡泊芬净作用烟曲霉菌48h后,细胞壁外层溶解脱落、细胞核及细胞器溶解消失,但细胞膜仍然完整。0.1%氟康唑对烟曲霉菌细胞壁及细胞膜均无影响。结论桂皮醛、卡泊芬净对烟曲霉菌均有较强的抗活性,但桂皮醛优于卡泊芬净。桂皮醛及卡泊芬净作用在烟曲霉菌细胞壁而不影响细胞膜,氟康唑对烟曲霉菌细胞壁及细胞膜均无影响。桂皮醛有望成为一种有效的靶向治疗曲霉菌感染的理想药物。

烟曲霉细胞壁作为药物靶标的鉴定研究

烟曲霉(Aspergillus fumigatus)作为侵袭性真菌感染的三大机会病原真菌之一,因其高致病率和高致死率而成为威胁人类健康的重大隐患。有限的抗真菌类药物以及近年来耐药性菌株的涌现使得寻找新的药物靶标并开发新型抗真菌药物迫在眉睫。真菌细胞壁作为真菌所特有的结构一直以来被认为是理想的药物靶标。本文概述了烟曲霉细胞壁结构及合成过程的相关研究进展,并分析了参与细胞壁各组分合成的酶作为药靶的可行性。

In vivo investigation of antimicrobial effects of cinnamaldehyde using immunosuppressed ICR mice with invasive pulmonary aspergillosis

Objective:Invasive pulmonary Aspergillus infection has the characteristics of high morbidity,difficult to be treated,poor prognosis and high mortality.This study aims to investigate the effects of cinnamaldehyde on 1,3-β-D-glucans in the pulmonary Aspergillus fumigatus cell wall to provide a basis for developing novel antifungal drugs.Methods:Immunosuppressed ICR mice were intranasally inoculated with 50μL of A.fumigatus suspension(1×10~7 CFU/m L)and then separated into two groups,for the experimental group cinnamaldehyde was orally administered at 240 mg/kg/d consecutively for 14 d.While for the control group,voriconazole was used to treat the fungus infection.Pulmonary tissues were then extracted for 1,3-β-D-glucans assay and electron microscopy.Results:The concentration of 1,3-β-D-glucans was significantly different between the cinnamaldehyde and voriconazole groups,which was(1160.89±364.96)pg/m L and(3885.94±845.45)pg/m L,respectively(P<0.01).Electron microscopy showed that 2-3 outer layers(1,3-β-D-glucan layer)of A.fumigatus cell wall were damaged and fell off,resulting in serious defect of the cell wall,but the cell membrane was clear and intact.Conclusion:Cinnamaldehyde has a significant influence on the integrity of 1,3-β-D-glucans in the pulmonary A.fumigatus cell wall,but the cell membrane is unaffected,suggesting that cinnamaldehyde has unique antifungal properties depending on its action against the 1,3-β-D-glucans on the pulmonary A.fumigatus cell wall.