Attaching and effacing pathogens modulate host mitochondrial structure and function.

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Anusha Harishankar, V K Viswanathan
{"title":"Attaching and effacing pathogens modulate host mitochondrial structure and function.","authors":"Anusha Harishankar, V K Viswanathan","doi":"10.1016/bs.ircmb.2023.03.001","DOIUrl":null,"url":null,"abstract":"<p><p>Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are human enteric pathogens that contribute significantly to morbidity and mortality worldwide. These extracellular pathogens attach intimately to intestinal epithelial cells and cause signature lesions by effacing the brush border microvilli, a property they share with other \"attaching and effacing\" (A/E) bacteria, including the murine pathogen Citrobacter rodentium. A/E pathogens use a specialized apparatus called a type III secretion system (T3SS) to deliver specific proteins directly into the host cytosol and modify host cell behavior. The T3SS is essential for colonization and pathogenesis, and mutants lacking this apparatus fail to cause disease. Thus, deciphering effector-induced host cell modifications is critical for understanding A/E bacterial pathogenesis. Several of the ∼20-45 effector proteins delivered into the host cell modify disparate mitochondrial properties, some via direct interactions with the mitochondria and/or mitochondrial proteins. In vitro studies have uncovered the mechanistic basis for the actions of some of these effectors, including their mitochondrial targeting, interaction partners, and consequent impacts on mitochondrial morphology, oxidative phosphorylation and ROS production, disruption of membrane potential, and intrinsic apoptosis. In vivo studies, mostly relying on the C. rodentium/mouse model, have been used to validate a subset of the in vitro observations; additionally, animal studies reveal broad changes to intestinal physiology that are likely accompanied by mitochondrial alterations, but the mechanistic underpinnings remain undefined. This chapter provides an overview of A/E pathogen-induced host alterations and pathogenesis, specifically focusing on mitochondria-targeted effects.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"377 ","pages":"65-86"},"PeriodicalIF":0.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321239/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International review of cell and molecular biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.ircmb.2023.03.001","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/4/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0

Abstract

Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are human enteric pathogens that contribute significantly to morbidity and mortality worldwide. These extracellular pathogens attach intimately to intestinal epithelial cells and cause signature lesions by effacing the brush border microvilli, a property they share with other "attaching and effacing" (A/E) bacteria, including the murine pathogen Citrobacter rodentium. A/E pathogens use a specialized apparatus called a type III secretion system (T3SS) to deliver specific proteins directly into the host cytosol and modify host cell behavior. The T3SS is essential for colonization and pathogenesis, and mutants lacking this apparatus fail to cause disease. Thus, deciphering effector-induced host cell modifications is critical for understanding A/E bacterial pathogenesis. Several of the ∼20-45 effector proteins delivered into the host cell modify disparate mitochondrial properties, some via direct interactions with the mitochondria and/or mitochondrial proteins. In vitro studies have uncovered the mechanistic basis for the actions of some of these effectors, including their mitochondrial targeting, interaction partners, and consequent impacts on mitochondrial morphology, oxidative phosphorylation and ROS production, disruption of membrane potential, and intrinsic apoptosis. In vivo studies, mostly relying on the C. rodentium/mouse model, have been used to validate a subset of the in vitro observations; additionally, animal studies reveal broad changes to intestinal physiology that are likely accompanied by mitochondrial alterations, but the mechanistic underpinnings remain undefined. This chapter provides an overview of A/E pathogen-induced host alterations and pathogenesis, specifically focusing on mitochondria-targeted effects.

病原体的附着和脱落会调节宿主线粒体的结构和功能。
肠致病性大肠埃希氏菌和肠出血性大肠埃希氏菌(EPEC 和 EHEC)是人类肠道病原体,对全世界的发病率和死亡率有重大影响。这些细胞外病原体与其他 "附着和脱落"(A/E)细菌(包括鼠类病原体棒状柠檬酸杆菌)具有相同的特性,即密切附着于肠上皮细胞,并通过脱落刷状缘微绒毛引起特征性病变。A/E病原体使用一种称为 III 型分泌系统(T3SS)的特殊装置,将特定蛋白质直接输送到宿主细胞膜,并改变宿主细胞的行为。T3SS 对于定殖和致病至关重要,缺乏这种装置的突变体不会致病。因此,破译效应器诱导的宿主细胞修饰对于了解 A/E细菌的致病机理至关重要。传递到宿主细胞的 20-45 种效应蛋白中,有几种会改变线粒体的不同特性,其中一些是通过与线粒体和/或线粒体蛋白的直接相互作用实现的。体外研究揭示了其中一些效应蛋白发挥作用的机理基础,包括它们的线粒体靶向、相互作用伙伴,以及由此对线粒体形态、氧化磷酸化和 ROS 产生、膜电位破坏和内在凋亡产生的影响。体内研究主要依靠啮齿动物/小鼠模型来验证体外观察的部分结果;此外,动物研究显示肠道生理学发生了广泛的变化,这些变化很可能伴随着线粒体的改变,但其机理基础仍未确定。本章概述了 A/E病原体诱导的宿主改变和发病机制,特别侧重于线粒体的靶向效应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
International review of cell and molecular biology
International review of cell and molecular biology BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY
CiteScore
7.70
自引率
0.00%
发文量
67
审稿时长
>12 weeks
期刊介绍: International Review of Cell and Molecular Biology presents current advances and comprehensive reviews in cell biology-both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信