Citrate and Metal Efflux by IceT

IceT 的柠檬酸盐和金属流出

基本信息

批准号：
8709707
负责人：
Elaine R. Frawley
金额：
$ 5.51万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8709707
关键词：
Alkaline Phosphatase Amino Acids Animals Antibiotics Bacteria Bacterial Antibiotic Resistance Bacterial Proteins Biological Biological Assay Biological Process C-terminal Cell membrane Chemistry Citrates Complex Coupled Development Electron Spin Resonance Spectroscopy Enterobacteriaceae Environment Enzymes Free Radicals Galactosidase Goals Growth Homologous Gene Host Defense Human Hydrogen Peroxide Immune system In Vitro Infection Iron Iron Overload Knowledge LacZ Genes Mass Spectrum Analysis Mediating Metabolism Metals Modeling Mus Mutation Nitric Oxide Oxidation-Reduction Paraquat Peroxides Plasma Play Predisposition Production Proteins Pump Regulation Resistance Role Salmonella Salmonella enterica Stress Structure-Activity Relationship System Vesicle Virulence catalyst enteric pathogen insight interest killings member mutant novel therapeutics pathogen public health relevance research study response

项目摘要

DESCRIPTION (provided by applicant): Salmonella enterica serovar Typhimurium (S. Typhimurium) is a model enteric pathogen. Like many pathogens, S. Typhimurium requires iron for survival both in the environment and in the host. However, when host defenses damage iron containing bacterial proteins, intracellular free iron acts as a catalyst for production of free radicals. IceT is a stress-induced transporter in the major facilitator superfamily that is conserved throughout the Enterobacteriaceae. Its expression in S. Typhimurium leads to efflux of iron and citrate, which protects the bacteria from a variety of stresses and antibiotics. The goal of this proposal is to further characterize this intrinsic mechanism of bacterial stress resistance and understand its role in S. Typhimurium virulence. This will be accomplished by characterizing the specific substrates transported by IceT and elucidating the chemistry of transport, examining structure-function relationships in the IceT protein, and characterizing a homologue of IceT, YieO, that is also found in S. Typhimurium and may play a complementary role in intrinsic resistance to host defenses and antibiotics. Experiments will be conducted in vitro, in culture, and in a murine model of infection. These studies will provide insight into the function of two representative members of the major facilitator superfamily and the role regulation of bacterial metabolism plays in resistance to stress.

描述（由申请人提供）：肠道沙门氏菌鼠伤寒（S. typhimurium）是一种模型肠病原体。像许多病原体一样，鼠伤寒链球菌需要铁在环境和宿主中的生存。但是，当宿主防御损害含有细菌蛋白的铁时，细胞内游离铁充当产生自由基的催化剂。 ICET是在整个肠杆菌科中保守的主要促进剂超家族中应力诱导的转运蛋白。它在鼠伤寒链球菌中的表达导致铁和柠檬酸盐的排出，从而保护细菌免受多种应激和抗生素的影响。该提案的目的是进一步表征这种细菌应激性抗性的内在机制，并了解其在伤寒链霉菌毒力中的作用。这将通过表征通过ICET运输的特定底物并阐明运输的化学，检查ICET蛋白中的结构功能关系，并表征ICET Yieo的同源物，在鼠伤寒链霉菌中也可以发现，并可能在宿主防御和抗抗物剂的固有抵抗力中起综合作用。实验将在体外，培养和鼠类感染模型中进行。这些研究将洞悉主要促进剂超家族的两个代表成员以及细菌代谢在抵抗压力方面的作用。