关键词: Antifungal drug Aspergillus fumigatus Fungal infection Invasive Osteolytic

Mesh : Antifungal Agents / pharmacology Itraconazole / pharmacology Voriconazole / pharmacology Amphotericin B / pharmacology Aspergillus fumigatus Bone and Bones

来  源:   DOI:10.1007/s11046-023-00817-y

Abstract:
BACKGROUND: Recently, the prevalence of invasive fungal infections has been on the rise, and one of the prevalent symptoms frequently observed is bone deterioration and bone loss.
METHODS: Using an in vitro model we studied how Aspergillus fumigatus invades the bone. Pathological analysis was then employed to observe the structure and distinctive features of the invading fungal elements within the bone invasion model. Meanwhile, the antifungal effects of itraconazole, voriconazole, posaconazole, and amphotericin B were evaluated.
RESULTS: The pathological findings showed that in the experimental group, fungal spores and hyphae invaded the bone tissue or were observed growing in the vicinity of the bone edge tissues, as indicated by both HE and PAS staining. In contrast, no fungal elements were observed in the control group, indicating that the in vitro bone invasion model of A. fumigatus was successfully constructed. Furthermore, the findings from the antifungal sensitivity test demonstrated that the lowest effective concentrations of antifungal drugs against the bone invasion model were as follows: 4 μg/ml for itraconazole, 0.5 μg/ml for voriconazole, 2 μg/ml for posaconazole, and 2 μg/ml for amphotericin B.
CONCLUSIONS: The successful construction of the bone invasion model of A. fumigatus has provided a solid basis for future investigations into the mechanisms underlying A. fumigatus bone invasion and the study of its virulence factors. Utilizing bone models is of utmost importance in advancing the development of novel antifungal treatment approaches, as well as in effectively preventing and treating fungal bone invasion and osteolytic diseases.
摘要:
背景:最近,侵袭性真菌感染的患病率一直在上升,经常观察到的常见症状之一是骨恶化和骨丢失。
方法:使用体外模型,我们研究了烟曲霉如何侵入骨骼。然后采用病理分析来观察骨侵袭模型中侵袭真菌元素的结构和独特特征。同时,伊曲康唑的抗真菌作用,伏立康唑,泊沙康唑,和两性霉素B进行评估。
结果:病理结果显示实验组,真菌孢子和菌丝侵入骨组织或在骨边缘组织附近观察到生长,如HE和PAS染色所示。相比之下,对照组没有观察到真菌元素,表明成功构建了烟曲霉菌的体外骨侵袭模型。此外,抗真菌敏感性试验的结果表明,抗真菌药物对骨侵袭模型的最低有效浓度如下:伊曲康唑为4μg/ml,伏立康唑0.5μg/ml,泊沙康唑为2μg/ml,
结论:烟曲霉菌骨侵袭模型的成功构建为今后研究烟曲霉菌骨侵袭机制及其毒力因子的研究提供了坚实的基础。利用骨骼模型对于推进新型抗真菌治疗方法的发展至关重要。以及有效预防和治疗真菌性骨侵袭和溶骨病。
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