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比较分析白色念珠菌菌株在小鼠胃肠道定植过程中的适应性。

Comparative Analysis of the Fitness of Candida albicans Strains During Colonization of the Mice Gastrointestinal Tract.

机构信息

Departamento de Microbiología y Parasitología-IRYCIS, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.

出版信息

Methods Mol Biol. 2022;2542:233-244. doi: 10.1007/978-1-0716-2549-1_17.

Abstract

Candida albicans populations present in the mammalian gastrointestinal tract are a major source of candidemia and subsequent severe invasive candidiasis in those individuals with acquired or congenital immune defects. Understanding the mechanisms used by this fungus to colonize this niche is, therefore, of primary importance to develop new therapeutic options that could lead to control its proliferation in the host. The recent popularization of models of commensalism in mice combined with the already powerful tools in C. albicans genetics allows to analyze the role of specific genes during colonization. Fitness can be analyzed for a specific C. albicans strain (test strain) by comparing its growth in vivo with an otherwise isogenic control strain via the analysis of the luminal content of the mouse gastrointestinal tract using flow cytometry, qPCR, or viable fungal cell counting. While all these procedures have limitations, they can be used to estimate the degree of adaptation of the test strain to the mammalian tract by determining its relative abundance with an internal control strain. By using specific genetically engineered C. albicans and mouse strains, antibiotic regimes, or even germ-free mice, this methodology allows to determine the role of the host immunological status, the bacterial microbiota, or individual fungal features (e.g., dimorphism) in the process of colonization of C. albicans of the mammalian gut.

摘要

哺乳动物胃肠道中存在的白色念珠菌种群是导致获得性或先天性免疫缺陷个体发生念珠菌血症和随后严重侵袭性念珠菌病的主要来源。因此,了解这种真菌定植该生态位的机制对于开发新的治疗方法至关重要,这些方法可能有助于控制其在宿主中的增殖。近年来,共生模型在小鼠中的普及,加上白色念珠菌遗传学中已经强大的工具,使得分析特定基因在定植过程中的作用成为可能。通过分析通过流式细胞术、qPCR 或活真菌细胞计数分析小鼠胃肠道管腔内容物,比较特定白色念珠菌菌株(测试菌株)与其在体内生长的 otherwise 同基因对照菌株的生长情况,可以分析特定菌株的适应性。虽然所有这些程序都有其局限性,但它们可以通过使用内部对照菌株来确定测试菌株与哺乳动物肠道的相对丰度,从而估计测试菌株对哺乳动物肠道的适应程度。通过使用特定的遗传工程白色念珠菌和小鼠菌株、抗生素方案甚至无菌小鼠,该方法可用于确定宿主免疫状态、细菌微生物群或单个真菌特征(例如,二态性)在哺乳动物肠道中白色念珠菌定植过程中的作用。

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