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细菌唾液酸糖苷酶在毒力和发病机制中的作用

Bacterial sialoglycosidases in Virulence and Pathogenesis.

作者信息

Sudhakara Preethi, Sellamuthu Iyappan, Aruni A Wilson

机构信息

Department of Genetic Engineering, SRM Institute of Science and Technology, Chennai 603203, India.

School of Medicine, California University of Science and Medicine, San Bernardino, CA 92408, USA.

出版信息

Pathogens. 2019 Mar 24;8(1):39. doi: 10.3390/pathogens8010039.

Abstract

Human oral microbiome and dysbiotic infections have been recently evidently identified. One of the major reasons for such dysbiosis is impairment of the immune system. Periodontitis is a chronic inflammatory disease affecting the tissues that surround and support the teeth. In the United States., approximately 65 million people are affected by this condition. Its occurrence is also associated with many important systemic diseases such as cardiovascular disease, rheumatoid arthritis, and Alzheimer's disease. Among the most important etiologies of periodontitis is a keystone bacterial pathogen. Keystone pathogens can orchestrate inflammatory disease by remodeling a normally benign microbiota causing imbalance between normal and pathogenic microbiota (dysbiosis). The important characteristics of causing dysbiosis are its virulence factors which cause effective subversion of host defenses to its advantage allowing other pathogens to grow. Some of the mechanisms involved in these processes are still not well-understood. However, various microbial strategies target host sialoglycoproteins for immune dysregulation. In addition, the enzymes that break down sialoglycoproteins and sialoglycans are the "sialoglycoproteases", resulting in exposed terminal sialic acid. This process could lead to pathogen-toll like receptor (TLR) interactions mediated through sialic acid receptor ligand mechanisms. Assessing the function of sialoglycoproteases, could pave the way to designing carbohydrate analogues and sialic acid mimetics to serve as drug targets.

摘要

人类口腔微生物群和生态失调感染最近已被明确识别。这种生态失调的主要原因之一是免疫系统受损。牙周炎是一种影响牙齿周围和支持组织的慢性炎症性疾病。在美国,大约6500万人受此疾病影响。它的发生还与许多重要的全身性疾病有关,如心血管疾病、类风湿性关节炎和阿尔茨海默病。牙周炎最重要的病因之一是一种关键的细菌病原体。关键病原体可通过重塑正常情况下良性的微生物群来引发炎症性疾病,导致正常微生物群与致病微生物群之间失衡(生态失调)。导致生态失调的重要特征是其毒力因子,这些因子可有效颠覆宿主防御机制以利于自身,从而使其他病原体得以生长。这些过程中涉及的一些机制仍未得到充分理解。然而,各种微生物策略针对宿主唾液糖蛋白以实现免疫失调。此外,分解唾液糖蛋白和唾液聚糖的酶是“唾液糖蛋白酶”,会导致末端唾液酸暴露。这一过程可能导致通过唾液酸受体配体机制介导的病原体与 Toll 样受体(TLR)相互作用。评估唾液糖蛋白酶的功能,可为设计碳水化合物类似物和唾液酸模拟物作为药物靶点铺平道路。

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