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srbA sRNA 对 TCA 循环基因的调控:对铜绿假单胞菌毒力和存活的影响。

Regulation of TCA cycle genes by srbA sRNA: Impacts on Pseudomonas aeruginosa virulence and survival.

机构信息

Department of Microbiology, University of Kalyani, Kalyani, 741235, India.

Department of Microbiology, University of Kalyani, Kalyani, 741235, India.

出版信息

Biochem Biophys Res Commun. 2024 Dec 10;737:150520. doi: 10.1016/j.bbrc.2024.150520. Epub 2024 Aug 8.

Abstract

Pseudomonas aeruginosa, an opportunistic bacterial pathogen of public health concern, is known for its metabolic versatility, adaptability in harsh environment, and pathogenic aggressiveness. P. aeruginosa relies on various regulatory networks modulated by small non-coding RNAs, which in turn influence different physiological traits such as metabolism, stress response, and pathogenesis. In this study, srbA sRNA has been shown to play a diverse role in regulating cellular metabolism and the production of different virulence factors in P. aeruginosa. srbA was found to control the TCA cycle, a key regulatory pathway for cellular metabolism and energy production, by regulating three main enzymes: citrate synthase (gltA), isocitrate dehydrogenase (icd), and α-ketoglutarate dehydrogenase E1 subunit (sucA) at both the transcriptional and translational levels. By modulating the TCA cycle, srbA could help the bacteria to adapt nutritional stress by lowering energy consumption. Additionally, srbA has been found to differentially regulate production of various virulence factors such as rhamnolipid, elastase, LasA protease, and pyocyanin under both nutrient-rich and nutrient-limiting conditions. It could also influence motilities in P. aeruginosa, linked to biofilm formation and pathogenicity. Thus, srbA might hold a promise in the research area for identifying virulence pathways and developing novel therapeutic targets to combat the global pathogenic threat of P. aeruginosa.

摘要

铜绿假单胞菌是一种具有公共卫生意义的机会致病菌,以其代谢多样性、在恶劣环境中的适应性和致病性攻击性而闻名。铜绿假单胞菌依赖于各种受小非编码 RNA 调节的调控网络,这些 RNA 反过来又影响不同的生理特征,如代谢、应激反应和发病机制。在这项研究中,srbA sRNA 被证明在调节铜绿假单胞菌细胞代谢和产生不同毒力因子方面发挥着多样化的作用。srbA 通过调节三个主要酶(柠檬酸合酶(gltA)、异柠檬酸脱氢酶(icd)和α-酮戊二酸脱氢酶 E1 亚基(sucA))在转录和翻译水平上控制 TCA 循环,TCA 循环是细胞代谢和能量产生的关键调节途径。通过调节 TCA 循环,srbA 可以帮助细菌通过降低能量消耗来适应营养应激。此外,srbA 已被发现可在营养丰富和营养有限的条件下差异调节各种毒力因子(如鼠李糖脂、弹性蛋白酶、LasA 蛋白酶和绿脓菌素)的产生。它还可以影响铜绿假单胞菌的运动性,这与生物膜形成和致病性有关。因此,srbA 可能在识别毒力途径和开发新的治疗靶点以对抗铜绿假单胞菌的全球致病威胁的研究领域中具有潜力。

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