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参与白色念珠菌生物膜形成和调控的分子决定因素。

Molecular Determinants Involved in Candida albicans Biofilm Formation and Regulation.

机构信息

Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, 492010, India.

出版信息

Mol Biotechnol. 2024 Jul;66(7):1640-1659. doi: 10.1007/s12033-023-00796-x. Epub 2023 Jul 6.

Abstract

Candida albicans is known for its pathogenicity, although it lives within the human body as a commensal member. The commensal nature of C. albicans is well controlled and regulated by the host's immune system as they live in the harmonized microenvironment. However, the development of certain unusual microhabitat conditions (change in pH, co-inhabiting microorganisms' population ratio, debilitated host-immune system) pokes this commensal fungus to transform into a pathogen in such a way that it starts to propagate very rapidly and tries to breach the epithelial barrier to enter the host's systemic circulations. In addition, Candida is infamous as a major nosocomial (hospital-acquired infection) agent because it enters the human body through venous catheters or medical prostheses. The hysterical mode of C. albicans growth builds its microcolony or biofilm, which is pathogenic for the host. Biofilms propose additional resistance mechanisms from host immunity or extracellular chemicals to aid their survival. Differential gene expressions and regulations within the biofilms cause altered morphology and metabolism. The genes associated with adhesiveness, hyphal/pseudo-hyphal growth, persister cell transformation, and biofilm formation by C. albicans are controlled by myriads of cell-signaling regulators. These genes' transcription is controlled by different molecular determinants like transcription factors and regulators. Therefore, this review has focused discussion on host-immune-sensing molecular determinants of Candida during biofilm formation, regulatory descriptors (secondary messengers, regulatory RNAs, transcription factors) of Candida involved in biofilm formation that could enable small-molecule drug discovery against these molecular determinants, and lead to disrupt the well-structured Candida biofilms effectively.

摘要

白色念珠菌以其致病性而闻名,尽管它作为共生成员存在于人体中。白色念珠菌的共生性质受到宿主免疫系统的很好控制和调节,因为它们生活在和谐的微环境中。然而,某些不寻常的小生境条件(pH 值变化、共栖微生物种群比例变化、宿主免疫系统功能减弱)会促使这种共生真菌转变为病原体,从而使其开始快速繁殖,并试图突破上皮屏障进入宿主的全身循环。此外,白色念珠菌是一种主要的医院获得性(医院获得性感染)病原体,因为它通过静脉导管或医疗假体进入人体。白色念珠菌的歇斯底里式生长方式构建了其微菌落或生物膜,这对宿主是致病的。生物膜提出了额外的抵抗机制,以帮助它们从宿主免疫或细胞外化学物质中存活。生物膜内的差异基因表达和调节导致形态和代谢的改变。与白色念珠菌的粘附性、菌丝/假菌丝生长、持久细胞转化和生物膜形成相关的基因受无数细胞信号调节剂控制。这些基因的转录受不同的分子决定因素(如转录因子和调节剂)控制。因此,本综述重点讨论了宿主免疫感知白色念珠菌生物膜形成过程中的分子决定因素、涉及生物膜形成的白色念珠菌调节描述符(第二信使、调节 RNA、转录因子),这些可能有助于针对这些分子决定因素发现小分子药物,并有效地破坏结构良好的白色念珠菌生物膜。

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