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Mechanoregulation of EHEC virulence

EHEC毒力的机械调节

基本信息

批准号：
9906845
负责人：
Anne-Marie Krachler
金额：
$ 45.6万
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 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9906845
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 Mechanics 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 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.

项目总结