Mechanoregulation of EHEC virulence

EHEC毒力的机械调节

基本信息

批准号：
10383740
负责人：
Anne-Marie Krachler
金额：
$ 38.23万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-02 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10383740
关键词：
Adhesions Affect Anti-Infective Agents Architecture Bacteria Bacterial Genes Biochemical Cells Chemicals Clinical Cues Development Diarrhea Disease Dose Enterocolitis Enterocytes Environment Escherichia coli EHEC Exposure to Feedback Fishes Gastrointestinal tract structure Gene Expression Gene Expression Regulation Genes Genetic Transcription Goals Hemolytic-Uremic Syndrome Human Infection Ingestion Intestines Knowledge Lead Life Style Liquid substance Mechanical Stress Membrane Microbiology Microfluidic Microchips Modality Modeling Molecular Mus Numbness Operon Optics Organism Pathway interactions Physiological Physiology Play Process Production Prokaryotic Cells Property Regulator Genes Research Role Sensory Shiga-Like Toxins Shock Signal Transduction Site Smell Perception Stimulus Stress System Taste Perception Testing Touch sensation Transcript Transcription Coactivator Translating Type III Secretion System Pathway Variant Virulence Virulence Factors Vision Vomiting Work Zebrafish base fighting fluid flow gene induction gut colonization host colonization human pathogen imaging approach in vivo insight mechanical force mechanical signal mechanical stimulus mechanotransduction microbial mutant novel pathogen pathogenic bacteria physical process preference pressure promoter response shear stress sound temporal measurement tissue tropism transcriptome sequencing

项目摘要

PROJECT SUMMARY Environmental sensing is at the basis of an organism’s ability to adapt its physiology to respond to changes in its niche. Over the past years, it has emerged that bacteria not only perceive and respond to chemical stimuli, but are capable of sensing and processing physical forces as an environmental cue. In the case of bacterial pathogens, we and others have shown that mechanical stimuli can act as a hallmark of host colonization and lead to activation of virulence genes. Despite this realisation, our mechanistic understanding of pathways and systems involved in mechanosensing, transduction and processing of physical forces is currently limited, as is our knowledge regarding the role of mechanoregulation within the host environment. The objective here is to understand how enterohemorrhagic E. coli, an important human pathogen, responds to physical force. In the human host, ingestion of EHEC can lead to enterocolitis and severe complications such as haemolytic uremic syndrome. These hallmarks of infection are caused by the concerted action of virulence factors, including colonization factors and Shiga-like toxins. Here, we will (a) characterize how virulence gene induction responds to physical forces, (b) determine the biochemical basis of signal transduction between membrane and transcriptional regulator, and (c) define the role of mechanosensing during the transitions between environmental and host-associated lifestyles. This work will reveal how EHEC perceive and process physical forces, and integrate these cues to coordinate their infection cycle. Such knowledge may highlight new targets for the development of anti-infective strategies that disable the pathogen by rendering it ‘numb’ to the host.

项目摘要环境敏感性是有机体适应其生理学以应对变化的能力的基础它的利基。在过去的几年中，已经出现了细菌不仅感知并对化学刺激做出反应但是能够将物理力作为环境提示传感和处理。在细菌的情况下病原体，我们和其他人表明，机械刺激可以作为宿主定植的标志和导致病毒基因的激活。尽管存在这种现实，我们对途径和目前我们对机械调节在主机环境中的作用的了解。这里的目的是了解重要人类病原体肠肠肠癌如何应对身体力量。在人宿主，摄入EHEC会导致小肠结肠炎和严重的并发症，例如溶血性尿毒症综合征。这些感染的标志是由病毒因素的一致作用引起的，包括定殖因子和类似志贺的毒素。在这里，我们将（a）表征病毒基因诱导的反应到物理力，（b）确定膜和膜之间信号转导的生化基础转录调节器，（c）定义机械机制在环境之间的过渡过程中的作用和与宿主相关的生活方式。这项工作将揭示EHEC的感知和处理身体力量，以及集成了这些提示以协调其感染周期。这样的知识可能会突出显示的新目标开发抗感染策略，通过将病原体“麻木”传播给宿主来禁用病原体。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Defective phagocyte association during infection of Galleria mellonella with Yersinia pseudotuberculosis is detrimental to both insect host and microbe.

DOI：
10.1080/21505594.2021.1878672
发表时间：
2021-12
期刊：
Virulence
影响因子：
5.2
作者：
Krachler AM;Sirisaengtaksin N;Monteith P;Paine CET;Coates CJ;Lim J
通讯作者：
Lim J

Bacterial outer membrane vesicles provide an alternative pathway for trafficking of Escherichia coli O157 type III secreted effectors to epithelial cells.

DOI：
10.1128/msphere.00520-23
发表时间：
2023-12-20
期刊：
mSphere
影响因子：
4.8
作者：
通讯作者：

Colonization of larval zebrafish (Danio rerio) with adherent-invasive Escherichia coli prevents recovery of the intestinal mucosa from drug-induced enterocolitis.

DOI：
10.1128/msphere.00512-23
发表时间：
2023-12-20
期刊：
mSphere
影响因子：
4.8
作者：
通讯作者：

Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model.

DOI：
10.1080/21505594.2020.1772652
发表时间：
2020-01-01
期刊：
Virulence
影响因子：
5.2
作者：
Huebinger RM;Do DH;Carlson DL;Yao X;Stones DH;De Souza Santos M;Vaz DP;Keen E;Wolf SE;Minei JP;Francis KP;Orth K;Krachler AM
通讯作者：
Krachler AM

Draft genome sequences of Pseudomonas strains zfem001-005 isolated from the intestine of larval zebrafish Danio rerio.

从斑马鱼斑马鱼幼虫肠道中分离出的假单胞菌菌株 zfem001-005 的基因组序列草案。

DOI：
10.1128/mra.00934-23
发表时间：
2024
期刊：
Microbiology resource announcements
影响因子：
0.8
作者：
Simbassa,SabonaB;Clark,Justin;Salazar,Keiko;Maresso,Anthony;Krachler,Anne-Marie
通讯作者：
Krachler,Anne-Marie