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Physiological Role for Cation Channels in Bacteria

细菌中阳离子通道的生理作用

基本信息

批准号：
10440266
负责人：
DEBORAH A. SIEGELE
金额：
$ 38.6万
依托单位：
TEXAS A&M UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10440266
关键词：
ATP Synthesis Pathway Acids Address Affect Antibiotics Bacillus subtilis Bacteria Bacterial Genome Bacterial Physiology Binding Biological Assay Biophysics Buffers Calorimetry Cations Cell physiology Cells Cellular Assay Chloride Channels Collection Consumption Data Development Electron Transport Equilibrium Escherichia coli Fluorescent Dyes Future Generations Genes Goals Growth In Vitro Ion Channel Ions Knock-out Knowledge Link Masks Measurable Measures Membrane Membrane Lipids Membrane Potentials Metabolism Modeling Molecular Mutation Organism Osmoregulation Phenotype Physiological Physiology Potassium Channel Prevalence Process Property Protein translocation Proteins Proton Pump Proton-Motive Force Protons Role Rotation Sequence Homology Solid Suppressor Mutations Testing Titrations Ursidae Family Work antimicrobial base biophysical properties cell growth cell motility experimental study genome sequencing knockout gene link protein negative affect new therapeutic target novel pH gradient patch clamp pathogen pathogenic bacteria proteoliposomes public health relevance reconstitution whole genome

项目摘要

SUMMARY Tetrameric cation channels are widely conserved among all species. While bacterial cation channels are often used in structural and biophysical assays as models for their eukaryotic homologs, little is known about their physiological role in bacteria. Escherichia coli (E. coli) possesses a single tetrameric K+ channel, kch, which bears high sequence homology to eukaryotic K+ channels. The generation of a viable ∆kch strain created as part of a large E. coli single-gene knockout collection led to kch being categorized as a non-essential protein, and the functional role of this putative K+ channel has remained unknown. Preliminary data demonstrates that Kch is actually an essential protein and that ∆kch strains acquire suppressor mutations in order to remain viable. These suppressor mutations provide important clues as to which metabolic processes utilize the channel and has revealed a potential physiological role for Kch. Based on these results, the following aims are proposed: (1) to characterize the functional properties of the kch K+ channel; (2) to determine how Kch function affects E. coli physiology; and (3) to expand these findings to other bacteria to elucidate the conserved functions of bacterial cation channels. The results of this work will expand knowledge on the role of cation channels in bacterial physiology. Given the prevalence of these channels in pathogenic bacteria, understanding how cation channels benefit them may reveal how these proteins could be exploited as novel drug targets.

总结四聚体阳离子通道在所有物种中广泛保守。虽然细菌阳离子通道通常在结构和生物物理测定中用作其真核同源物的模型，对其结构和生物物理特性知之甚少。细菌的生理作用。大肠埃希菌（E. coli）具有单个四聚体K+通道kch，与真核细胞的K+通道具有高度的序列同源性。一个可行的Replikch菌株的产生，一个大的E。大肠杆菌单基因敲除收集导致kch被归类为非必需蛋白，这种推定的K+通道的功能作用仍然未知。初步数据表明，Kch是实际上是一种必需的蛋白质，并且Replikch菌株获得抑制突变以保持活力。这些抑制基因突变提供了重要的线索，代谢过程中利用的渠道，并已揭示了Kch的潜在生理作用。基于这些结果，提出了以下目标：（1）（2）确定Kch功能对E.杆菌（3）将这些发现扩展到其他细菌，以阐明细菌的保守功能阳离子通道这项工作的结果将扩大知识的作用，阳离子通道在细菌 physiology.鉴于这些通道在致病菌中的普遍存在，了解阳离子通道如何这可能揭示了这些蛋白质如何被开发为新的药物靶点。