The roles of sRNA in the physiology and pathogenesis of Mycobacterium abscessus and other mycobacteria

sRNA在脓肿分枝杆菌和其他分枝杆菌生理和发病机制中的作用

• 批准号: 10303736
• 负责人: Scarlet Sara Shell
• 金额: $ 22.12万
• 依托单位: WORCESTER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-24 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10303736
• 关键词: Address; Affect; Animal Model; Antibiotic Resistance; Antibiotics; Bacteria; Biology; Cells; Clinical; Deterioration; Development; Disease; Drug resistance; ELF3 gene; Foundations; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Engineering; Genus Mycobacterium; Goals; Infection; Knowledge; Leprosy; Libraries; Lung diseases; Lung infections; Mediating; Messenger RNA; Metabolism; Molecular Chaperones; Molecular Genetics; Mycobacterium abscessus; Mycobacterium smegmatis; Organism; Pathogenesis; Pathway interactions; Patients; Permeability; Phenotype; Physiological; Physiological Processes; Physiology; Play; Prevalence; Proteins; RNA; RNA-Binding Proteins; Regulation; Resistance; Resistance development; Role; Sequence Homology; Small RNA; Stress; System; Technology; Treatment Failure; Tuberculosis; Untranslated RNA; Virulence; Virulence Factors; Virulent; Work; antibiotic tolerance; biological adaptation to stress; cell envelope; cohort; cystic fibrosis patients; effective therapy; emerging pathogen; genetic manipulation; human disease; improved; mRNA Stability; mutant; mycobacterial; novel; pathogen; pathogenic bacteria; pulmonary function; response; ribonuclease E; synergism; tool

Project summary/abstract Mycobacteria cause several human diseases including tuberculosis and leprosy. Mycobacterium abscessus causes serious lung disease particularly in cystic fibrosis patients. M. abscessus infections are especially difficult to treat because the bacteria are intrinsically resistant to many antibiotics. Development of improved therapies requires more information about how M. abscessus regulates its physiology in response to the stressful conditions that it encounters during infection. Regulation of gene expression is a key component of stress responses for most organisms. Small RNAs (sRNAs) have been found to play important roles in gene regulation in a number of other bacterial pathogens. However, little is known about how sRNAs regulate gene expression and contribute to the pathogenesis of mycobacteria, particularly M. abscessus. There is less known about the biology of M. abscessus in general compared to other better-studied mycobacteria, in large part because M. abscessus is difficult to genetically manipulate. We will harness state-of-the-art technologies for both genetic engineering of M. abscessus and the study of sRNAs, in order to address some of the most pressing questions in mycobacterial sRNA biology. We will (1) determine the mechanisms by which the sRNA B11 regulates activity of a secretion system and other virulence-associated phenotypes in M. abscessus, and (2) identify proteins involved in mycobacterial sRNA function and characterize their roles. The proposed studies will provide foundational knowledge needed to facilitate development of more effective treatments for mycobacterial diseases.

项目摘要/摘要 分枝杆菌引起几种人类疾病，包括结核病和麻风病。分枝杆菌脓肿 引起严重的肺部疾病，特别是在囊性纤维化患者中。 M.腹肌感染尤其是 由于细菌对许多抗生素具有本质上的抗性，因此很难治疗。改进的发展 疗法需要更多有关M. abcessus如何调节其生理学的更多信息 在感染期间遇到的压力条件。基因表达的调节是 对大多数生物的压力反应。已经发现小型RNA（SRNA）在基因中起重要作用 许多其他细菌病原体中的调节。但是，关于SRNA如何调节基因的知之甚少 表达并有助于分枝杆菌的发病机理，尤其是脓肿。鲜为人知 与其他研究的分枝杆菌相比 因为腹部脱节很难在遗传上操纵。我们将利用最先进的技术 为了解决一些最多的人，腹肌分枝杆菌的基因工程和SRNA的研究都是 分枝杆菌SRNA生物学中提出问题。我们将（1）确定SRNA的机制 B11调节分泌系统的活性和其他与毒素相关的表型，以及 （2）确定涉及分枝杆菌SRNA功能的蛋白质并表征其作用。提出的研究 将提供所需的基本知识，以促进开发更有效的治疗方法 分枝杆菌疾病。