Physiological and Developmental Role of Bacterial Ser/Thr Kinases

细菌丝氨酸/苏氨酸激酶的生理和发育作用

• 批准号: 10501586
• 负责人: Elizabeth Libby
• 金额: $ 39.25万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10501586
• 关键词: Animal Model; Anti-Infective Agents; Antibiotic Resistance; Antibiotics; Appearance; Architecture; Bacillus subtilis; Bacteria; Bacterial Physiology; Behavior; Cell division; Cell physiology; Cells; Clinical; Competence; Cues; Development; Disease; Environment; Enzymes; Generations; Germination; Goals; Health; Human; Laboratories; Life Style; Microbial Biofilms; Pathway interactions; Phenotype; Phosphoric Monoester Hydrolases; Phosphotransferases; Physiological; Population; Post-Translational Protein Processing; Protein-Serine-Threonine Kinases; Regulation; Role; Signal Transduction; System; Transcriptional Regulation; Virulence; antibiotic tolerance; cell growth; improved; insight; response; transcription factor

Project Summary Bacteria employ signaling systems to sense and respond to their environment. This allows them to adjust their cellular physiology and collective behavior in response to environmental cues. One subset of these systems are the Hanks-type serine/threonine kinases and phosphatases. These signaling systems have been shown to be critical, and even often essential, for bacterial physiology, including cell growth and division, antibiotic tolerance and resistance, sporulation and germination, virulence, and biofilm formation. To accomplish this, these systems can regulate cellular function through direct post-translational modification of enzymes, or control transcription by adding an additional layer of regulation to the activity of transcription factors from other pathways. As a result, the activity of Hanks-type Ser/Thr signaling systems remains poorly understood, particularly at the single-cell level, where these systems are known to regulate the appearance of rare cells with extreme phenotypes such as increased antibiotic resistance and bacterial virulence. The long-term goal of my laboratory is to explore how these signaling systems regulate population and single-cell-level phenotypes and thereby to understand their contribution to human health and disease. To do so, we will 1) perform a mechanistic and quantitative study of conserved bacterial Hanks-type Ser/Thr kinase-phosphatase systems, focused on understanding how their regulatory architecture enables the generation of rare cells in bacterial populations with extreme phenotypes, 2) determine the role of these signaling systems in developmental transitions such as competence, biofilm formation, and sporulation. Initially we will focus on these systems in the model organism Bacillus subtilis, with the long-term goal to uncover the conserved features that can be generalized to other, less genetically tractable, and clinically important bacteria.

项目摘要 细菌采用信号系统来感知和响应其环境。这使他们可以调整 细胞生理和集体行为响应环境线索。这些系统的一个子集 是汉克斯型丝氨酸/苏氨酸激酶和磷酸酶。这些信号系统已显示为 对于细菌生理，包括细胞生长和分裂，抗生素至关重要，甚至通常至关重要 耐受性和抗性，孢子形成和发芽，毒力和生物膜形成。为此， 这些系统可以通过酶的直接翻译后修饰来调节细胞功能，或 通过在转录因子的活性中添加额外的调节来控制转录 途径。结果，汉克斯型SER/THR信号系统的活性仍然很了解， 特别是在单细胞水平上，其中已知这些系统调节稀有细胞的外观 具有极端表型，例如抗生素耐药性和细菌毒力增加。长期目标 我的实验室是探索这些信号系统如何调节种群和单细胞级表型 从而了解他们对人类健康和疾病的贡献。为此，我们将1）执行 保守细菌汉克斯型Ser/THR激酶 - 磷酸酶系统的机械和定量研究， 专注于了解其调节结构如何使细菌中的稀有细胞产生 具有极端表型的种群，2）确定这些信号系统在发育中的作用 诸如能力，生物膜形成和孢子形成之类的过渡。最初，我们将专注于这些系统 模型有机杆菌枯草芽孢杆菌，其长期目标是揭示可以是可以是的保守特征 概括到其他遗传学上不太遗传和临床上重要的细菌。