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细菌遗传毒素的传递、结构和功能。

Delivery, structure, and function of bacterial genotoxins.

机构信息

Department of Microbiology and Immunology, Cornell University, Ithaca, NY, USA.

出版信息

Virulence. 2022 Dec;13(1):1199-1215. doi: 10.1080/21505594.2022.2097417.

Abstract

Bacterial genotoxins are peptide or protein virulence factors produced by several pathogens, which make single-strand breaks (SSBs) and/or double-strand DNA breaks (DSBs) in the target host cells. If host DNA inflictions are not resolved on time, host cell apoptosis, cell senescence, and/or even bacterial pathogen-related cancer may occur. Two multi-protein AB toxins, cytolethal distending toxin (CDT) produced by over 30 bacterial pathogens and typhoid toxin from Typhi, as well as small polyketide-peptides named colibactin that causes the DNA interstrand cross-linking and subsequent DSBs is the most well-characterized bacterial genotoxins. Using these three examples, this review discusses the mechanisms by which these toxins deliver themselves into the nucleus of the target host cells and exert their genotoxic functions at the structural and functional levels.

摘要

细菌遗传毒素是由多种病原体产生的肽类或蛋白质毒力因子,可在靶宿主细胞中造成单链断裂(SSBs)和/或双链 DNA 断裂(DSBs)。如果宿主 DNA 损伤不能及时得到解决,宿主细胞凋亡、细胞衰老,甚至与细菌病原体相关的癌症可能会发生。两种多蛋白 AB 毒素,即超过 30 种细菌病原体产生的细胞致死扩张毒素(CDT)和来自伤寒沙门氏菌的伤寒毒素,以及被称为 colibactin 的小聚酮肽,可导致 DNA 链间交联和随后的 DSBs,是最具特征性的细菌遗传毒素。本文将使用这三个例子,讨论这些毒素将自身递送至靶宿主细胞核内并在结构和功能水平上发挥其遗传毒性功能的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cc1/9341358/b1406791086d/KVIR_A_2097417_F0001_OC.jpg

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