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: 10672307
• 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/10672307
• 关键词: 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; Serine; Signal Transduction; System; Transcriptional Regulation; Virulence; antibiotic tolerance; cell growth; improved; insight; model organism; 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.

项目概要 细菌利用信号系统来感知环境并对其做出反应。这使他们能够调整自己的 响应环境线索的细胞生理学和集体行为。这些系统的一个子集 是 Hanks 型丝氨酸/苏氨酸激酶和磷酸酶。这些信号系统已被证明可以 对于细菌生理学（包括细胞生长和分裂、抗生素）至关重要，甚至常常是必需的 耐受性和抗性、孢子形成和发芽、毒力和生物膜形成。为了实现这一目标， 这些系统可以通过酶的直接翻译后修饰来调节细胞功能，或者 通过对其他转录因子的活性添加额外的调控层来控制转录 途径。因此，Hanks 型 Ser/Thr 信号系统的活性仍然知之甚少， 特别是在单细胞水平上，已知这些系统可以调节稀有细胞的出现 具有极端表型，例如抗生素耐药性和细菌毒力增加。长期目标是 我的实验室是探索这些信号系统如何调节群体和单细胞水平的表型 从而了解它们对人类健康和疾病的贡献。为此，我们将 1) 执行 保守细菌 Hanks 型 Ser/Thr 激酶磷酸酶系统的机制和定量研究， 专注于了解它们的调控结构如何能够在细菌中生成稀有细胞 具有极端表型的人群，2）决定这些信号系统在发育中的作用 能力、生物膜形成和孢子形成等转变。最初我们将重点关注这些系统 模式生物枯草芽孢杆菌，其长期目标是发现可用于研究的保守特征 普遍适用于其他遗传上不易处理且临床上重要的细菌。