Calcium signaling in Mycobacterium tuberculosis

结核分枝杆菌中的钙信号传导

• 批准号: 10726978
• 负责人: Christoph Grundner
• 金额: $ 30.92万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-19 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10726978
• 关键词: Adopted; Bacteria; Bacterial Physiology; Calcium; Calcium Binding; Calcium Channel; Calcium Signaling; Calcium ion; Calcium-Binding Proteins; Cells; Cellular Stress; Chemicals; Communication; Cues; Data; Defect; Dependence; Eukaryota; Eukaryotic Cell; Exposure to; Flow Cytometry; Fluorescence Resonance Energy Transfer; Growth; Homeostasis; Infection; Kinetics; Knock-out; Ligand Binding; Ligands; Link; Macrophage; Maintenance; Maps; Mass Spectrum Analysis; Measures; Membrane; Mus; Mycobacterium tuberculosis; Pathogenesis; Pathogenicity; Phenotype; Phosphorylation; Physiological; Physiology; Proteins; Proteome; Proteomics; Reporter; Role; Signal Transduction; Stress; System; Testing; Time; VDAC1 gene; experimental study; human pathogen; inorganic phosphate; model organism; mutant; novel; protein profiling; response; tool; uptake

ABSTRACT Calcium (Ca2+) is a major signaling mechanism in eukaryotic cells, but although Ca2+ signaling has ancient origins, it is not well understood in bacteria. Several bacteria have been shown to maintain a low intracellular Ca2+ concentration, which is the basis for Ca2+ signaling in eukaryotes. In addition, some bacterial Ca2+- binding proteins and putative transporters have been identified, suggesting the presence of a bacterial Ca2+ signaling system analogous to that in eukaryotes. However, many fundamental questions about bacterial Ca2+ signaling remain, from maintenance of Ca2+ gradients to Ca2+ triggers, Ca2+ binding proteins, Ca2+ storage, and finally the effects of changing Ca2+ concentrations on bacterial physiology and pathogenesis. Using a FRET-based Ca2+ reporter system in Mycobacterium tuberculosis (Mtb) that allows for precise, real time measuring of intracellular Ca2+ levels, we will explore these fundamental questions about Ca2+ signaling in Mtb. We will use a novel proteomic approach, thermal protein profiling, to globally detect Ca2+ binding proteins in Mtb. We also identified a novel Ca2+ porin and will use a porin knockout strain to test for the role of Ca2+ in Mtb pathogenesis. Together, we will leverage these new tools to test the hypothesis that Mtb maintains a Ca2+ signaling system analogous to that in many eukaryotes and will begin to dissect the physiologic and pathogenic implications of Ca2+ homeostasis in Mtb.

摘要