CRK1基因缺失影响白念珠菌与肠粘膜相互作用的研究.docx

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摘要
白念珠菌（Candida albicans）是一种常见的真菌，可引起多种人类疾病。肠道是白念珠菌感染的重要部位之一，该菌可通过与肠道上皮细胞相互作用来感染人体。CRK1基因是编码特定蛋白质的基因，通过影响白念珠菌内在细胞信号转导通路中的几个关键事件参与其与肠粘膜细胞之间的相互作用。通过CRK1基因缺失基因编码的蛋白质无法正常功能，因此无法在相互作用中发挥作用，从而影响了白念珠菌的生理特性和致病性。
本文通过文献综述的方法，简要介绍了白念珠菌与肠道内皮细胞相互作用的机制及其在感染与疾病发生中的作用，并详细探讨了CRK1基因在该过程中的生物学意义。文章旨在进一步加深对白念珠菌与其寄主之间相互作用的理解，并为开发新的抗真菌药物提供理论基础。
关键词：白念珠菌；CRK1基因；肠道上皮细胞；相互作用；致病性
Introduction
White-nosed fungus (Candida albicans) is a common fungal species that can cause a variety of human diseases. The intestine is one of the important sites of infection by this fungus, where it interacts with intestinal epithelial cells to infect humans. The CRK1 gene encodes a specific protein that participates in the interaction between C. albicans and intestinal mucosal cells by affecting several key events in the intracellular signaling pathway of the fungus. Loss of the CRK1 gene results in dysfunctional protein production, leading to the inability to play a role in the interaction, thereby affecting the physiological characteristics and pathogenicity of C. albicans.
The purpose of this review is to briefly introduce the mechanism of interaction between C. albicans and intestinal epithelial cells and its role in infection and disease occurrence, and to explore the biological significance of the CRK1 gene in this process in detail. The article aims to further deepen our understanding of the interaction between C. albicans and its host, and provide a theoretical basis for the development of new antifungal drugs.
Interaction between C. albicans and Intestinal Epithelial Cells
C. albicans is a common member of the human microbiome that normally inhabits mucous membranes such as the oral cavity, gastrointestinal tract, and genitourinary tract. However, under certain conditions, such as changes in host immunity and antibiotic treatment, it becomes pathogenic and can cause a wide range of infections including thrush, vaginitis, and systemic infections (Sudbery, 2011). It has been reported that C. albicans can interact with intestinal epithelial cells and invade intestinal tissue, leading to local or systemic infections (Brown and Netea, 2015).
The interaction process between C. albicans and intestinal epithelial cells can be divided into several stages, including adherence, invasion, and intracellular survival (Naglik et al., 2019). Adhesion is the first stage of invasion, in which fungal cells attach to the surface of host cells through specific adhesion molecules, mainly involving proteins such as ALS (agglutinin-like sequence) and Hwp1 (hyphal wall protein 1) (Phan et al., 2007). After adhesion, C. albicans can penetrate host cells by forming invaginations, a process known as endocytosis, and enter the cytoplasm. Once inside the cells, C. albicans produces filamentous hyphae that protrude from host cells and invade adjacent cells (Mayer and Wilson, 2015).
CRK1 Gene and its Biological Significance
The CRK1 gene is a conserved gene found in many pathogenic fungal species, including C. albicans. Studies have shown that the CRK1 gene encodes a protein kinase that is involved in the regulation of several cellular processes, including cell cycle progression, cell wall integrity, and stress response (Lev et al., 2013). The CRK1 protein is also involved in the regulation of intracellular signaling pathways through phosphorylation of target proteins, including the Hog1 stress response pathway and the cell cycle checkpoint kinase Swe1 (Lev et al., 2013).
In C. albicans, the CRK1 gene has been reported to play an important role in the fungus's ability to interact with host cells. Studies have shown that CRK1 is required for the production of hyphae, a critical factor in the virulence of C. albicans (Brand et al., 2015). In addition, CRK1 is involved in the activation of several signaling pathways in response to host infection. For example, in response to host signals, CRK1 activates the kinase Cek1, which in turn activates the transcription factor Cph1 (Sudbery, 2011). The Cph1-dependent pathway, in turn, is involved in the upregulation of several virulence factors, including ALS3, which plays an important role in adhesion (Naglik et al., 2019).
In addition to its role in virulence, the CRK1 gene is also involved in antifungal drug resistance. Studies have shown that the loss of CRK1 can lead to increased susceptibility to several antifungal agents, including azoles and echinocandins (Kumamoto and Vinces, 2011).
Conclusion
The interaction between C. albicans and intestinal epithelial cells plays an important role in the pathogenesis of C. albicans infection. The CRK1 gene, encoding a protein kinase that plays a role in several cellular processes, is involved in the fungus's ability to interact with host cells, in particular through its role in hyphal growth and virulence factor regulation. The loss of CRK1 can lead to defects in the interaction between C. albicans and intestinal epithelial cells and increased susceptibility to antifungal agents. The biological significance of the CRK1 gene highlights its potential as a therapeutic target for the treatment of C. albicans infections.