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针对蛋白质稳态网络进行分枝杆菌药物研发。

Targeting the Proteostasis Network for Mycobacterial Drug Discovery.

作者信息

Lupoli Tania J, Vaubourgeix Julien, Burns-Huang Kristin, Gold Ben

机构信息

Department of Microbiology and Immunology , Weill Cornell Medicine , 413 East 69th Street , New York , New York 10021 , United States.

出版信息

ACS Infect Dis. 2018 Apr 13;4(4):478-498. doi: 10.1021/acsinfecdis.7b00231. Epub 2018 Mar 2.

DOI:10.1021/acsinfecdis.7b00231
PMID:29465983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5902792/
Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the world's deadliest infectious diseases and urgently requires new antibiotics to treat drug-resistant strains and to decrease the duration of therapy. During infection, Mtb encounters numerous stresses associated with host immunity, including hypoxia, reactive oxygen and nitrogen species, mild acidity, nutrient starvation, and metal sequestration and intoxication. The Mtb proteostasis network, composed of chaperones, proteases, and a eukaryotic-like proteasome, provides protection from stresses and chemistries of host immunity by maintaining the integrity of the mycobacterial proteome. In this Review, we explore the proteostasis network as a noncanonical target for antibacterial drug discovery.

摘要

由结核分枝杆菌（Mtb）引起的结核病（TB）仍然是世界上最致命的传染病之一，迫切需要新的抗生素来治疗耐药菌株并缩短治疗时间。在感染过程中，Mtb会遇到许多与宿主免疫相关的压力，包括缺氧、活性氧和氮物种、轻度酸性、营养饥饿以及金属螯合和中毒。由伴侣蛋白、蛋白酶和类真核蛋白酶体组成的Mtb蛋白质稳态网络通过维持分枝杆菌蛋白质组的完整性，为抵御宿主免疫的压力和化学物质提供保护。在本综述中，我们探讨了蛋白质稳态网络作为抗菌药物发现的非传统靶点。

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