Virulence assessment of six major pathogenic Candida species in the mouse model of invasive candidiasis caused by fungal translocation
Virulence assessment of six major pathogenic Candida species in the mouse model of invasive candidiasis caused by fungal translocation
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DOI：
10.1038/s41598-020-60792-y
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发表时间：
2020-03-02
影响因子：
4.6
通讯作者：
Mukae, Hiroshi
中科院分区：
文献类型：
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作者：
Hirayama, Tatsuro;Miyazaki, Taiga;Mukae, Hiroshi
胃肠道定植被认为是念珠菌血症的主要来源;然而，很少有建立的小鼠模型可模拟这种感染途径。因此，我们开发了一个可重复的小鼠模型，侵袭性念珠菌病发起的真菌易位和比较的毒力的六个主要致病念珠菌。给小鼠喂食低蛋白饮食，然后用念珠菌细胞进行胃内接种。然后给予口服抗生素和环磷酰胺以促进念珠菌细胞的定植和随后的传播。感染白色念珠菌和热带念珠菌的小鼠死亡率高于感染其他四种念珠菌的小鼠。在毒力较低的菌种中，光滑念珠菌和近平滑念珠菌的粪便滴度高于克柔念珠菌和季也蒙念珠菌。C. parapsilosis和C. krusei在肝脏和肾脏中的含量显著高于C.季也蒙地。在组织学上，C.白色念珠菌的致病性最强，可侵入肠粘膜和肝组织，引起明显的坏死。总体而言，该模型允许分析念珠菌菌株在个体小鼠中的毒力特征，包括肠道定植、渗透到肠粘膜、侵入血管以及随后导致致死性感染的传播。
Gastrointestinal colonization has been considered as the primary source of candidaemia; however, few established mouse models are available that mimic this infection route. We therefore developed a reproducible mouse model of invasive candidiasis initiated by fungal translocation and compared the virulence of six major pathogenic Candida species. The mice were fed a low-protein diet and then inoculated intragastrically with Candida cells. Oral antibiotics and cyclophosphamide were then administered to facilitate colonization and subsequent dissemination of Candida cells. Mice infected with Candida albicans and Candida tropicalis exhibited higher mortality than mice infected with the other four species. Among the less virulent species, stool titres of Candida glabrata and Candida parapsilosis were higher than those of Candida krusei and Candida guilliermondii. The fungal burdens of C. parapsilosis and C. krusei in the livers and kidneys were significantly greater than those of C. guilliermondii. Histopathologically, C. albicans demonstrated the highest pathogenicity to invade into gut mucosa and liver tissues causing marked necrosis. Overall, this model allowed analysis of the virulence traits of Candida strains in individual mice including colonization in the gut, penetration into intestinal mucosa, invasion into blood vessels, and the subsequent dissemination leading to lethal infections.