Why put yourself on a pedestal? The pathogenic role of the A/E pedestal

IF 2.9 3区 医学 Q3 IMMUNOLOGY
M. V. Miner, I. Rauch
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Abstract

The study of enterobacterial pathogens is of critical importance, given the nearly 63,000 annual diarrheagenic Escherichia coli (E. coli)-related deaths worldwide (1, 2). In particular, enteropathogenic E. coli (EPEC) is a leading cause of infantile diarrhea, often contracted through the fecal-oral route via food or water (3). Attaching and effacing (A/E) pathogens, like EPEC, are named for their signature lesion on the intestinal epithelium during infection. The characteristics of these attaching and effacing lesions are effacement of the intestinal brush border, intimate attachment to the host epithelium, and the formation of actin-rich pedestals below the site of bacterial adherence. These pedestals are derived from bacterial-driven actin nucleation inside the host cell, creating a protrusion in the plasma membrane. Enterohemorrhagic E. coli (EHEC) is another human A/E pathogen that is similar to EPEC but can be distinguished from EPEC by its pathogenic and geographic features. Although EPEC is prevalent in low- and middle-income countries, EHEC is pervasive in developed countries. EPEC preferentially infects the small intestine, and EHEC preferentially infects the colon. Additionally, only EHEC produces Shiga toxin (Stx) that can inhibit protein synthesis in eukaryotic cells and is a cause of many of the systemic symptoms experienced, including long-term renal damage and hemolytic uremic syndrome (4, 5). Regardless of their clinical differences, both EPEC and EHEC are often studied using the murine pathogen Citrobacter rodentium (C. rodentium) as a proxy (6–8). All three pathogens encode the Locus of enterocyte effacement (LEE) pathogenicity island, which encodes a type III secretion system and is required for virulence. C. rodentium possesses the same LEE pathogenicity island-encoded effectors that are required for EPEC and EHEC virulence (9–11). However, the three AE pathogens have other effectors that are not a part of the LEE pathogenicity island, contributing to distinct characteristics in each pathogen. These A/E lesion pathogens are a continuous object of study due, in part, to their unique ability to form pedestals and the unknown role the pedestals play in infection.
为什么把自己放在神坛上?A/E基座的致病作用
鉴于全球每年有近 6.3 万例与腹泻致病性大肠杆菌(E. coli)相关的死亡病例(1, 2),研究肠道细菌病原体至关重要。尤其是肠致病性大肠杆菌(EPEC)是婴儿腹泻的主要病因,通常是通过食物或水的粪口途径感染的(3)。附着和脱落(A/E)病原体,如 EPEC,因其在感染期间在肠道上皮细胞上的特征性附着而得名。这些附着和脱落病变的特征是肠道刷状缘脱落、与宿主上皮亲密附着以及在细菌附着部位下方形成富含肌动蛋白的基座。肠出血性大肠杆菌(EHEC)是另一种人类 A/E病原体,与 EPEC 相似,但可通过其致病性和地理特征与 EPEC 区分开来。虽然 EPEC 常见于中低收入国家,但 EHEC 却普遍存在于发达国家。EPEC 主要感染小肠,而 EHEC 主要感染结肠。此外,只有 EHEC 能产生志贺毒素(Stx),该毒素可抑制真核细胞的蛋白质合成,是导致许多全身症状的原因,包括长期肾损害和溶血性尿毒症综合征(4,5)。尽管 EPEC 和 EHEC 在临床上存在差异,但它们经常被用作鼠类病原体棒状杆菌(C. rodentium)的替代物进行研究(6-8)。这三种病原体都编码肠细胞脱落(LEE)致病基因,该基因编码 III 型分泌系统,是致病力所必需的。鼠伤寒杆菌也拥有同样的由 LEE 致病性岛编码的效应器,这些效应器是EPEC 和 EHEC 致病性所必需的(9-11)。然而,这三种 AE 病原体还具有不属于 LEE 致病性岛的其他效应器,从而使每种病原体都具有不同的特征。这些 A/E 病变病原体是一个持续的研究对象,部分原因是它们具有形成基座的独特能力,而基座在感染中所起的作用尚不清楚。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Infection and Immunity
Infection and Immunity 医学-传染病学
CiteScore
6.00
自引率
6.50%
发文量
268
审稿时长
3 months
期刊介绍: Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.
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