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

项目摘要/摘要 分枝杆菌会引起几种人类疾病，包括肺结核和麻风病。脓肿分枝杆菌 会导致严重的肺部疾病，尤其是囊性纤维化患者。尤其是脓肿分枝杆菌感染 很难治疗，因为这种细菌对许多抗生素都有内在的抗药性。改进型汽车的发展 治疗需要更多关于脓肿分枝杆菌如何调节其生理反应的信息 它在感染过程中遇到的压力条件。基因表达的调控是基因表达的关键组成部分 大多数生物体的应激反应。小RNA(SRNAs)已被发现在基因中发挥重要作用 对其他一些细菌病原体的监管。然而，人们对sRNA如何调控基因知之甚少。 在分枝杆菌，尤其是脓肿分枝杆菌的致病过程中起重要作用。还有一些鲜为人知的 关于脓肿分枝杆菌的生物学与其他研究较好的分枝杆菌相比，在很大程度上 因为脓肿分支杆菌很难在基因上进行控制。我们将利用最先进的技术来 脓肿分支杆菌的基因工程和sRNA的研究，以解决一些最 分枝杆菌SRNA生物学中的紧迫问题。我们将(1)确定SRNA的机制 B11调节脓肿分支杆菌分泌系统的活性和其他与毒力相关的表型，以及 (2)鉴定与分枝杆菌sRNA功能相关的蛋白质并鉴定其功能。建议进行的研究 将提供必要的基础知识，以促进开发更有效的治疗方法 分枝杆菌病。

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.