Zhao Runping, Xu Lei, Chen Jieyun, Yang Yanxian, Guo Xilong, Dai Min, Tian Guo-Bao, Qin Li-Na
School of Laboratory Medicine, Chengdu Medical College, Chengdu, China.
Zhongshan School of Medicine, Advanced Medical Technology Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Microbiol. 2024 Sep 30;15:1450085. doi: 10.3389/fmicb.2024.1450085. eCollection 2024.
is one of the chief pathogens that cause chronic and recurrent infections. Failure of the antibiotics to curb the infections contributes to relapse and is an important reason for the high mortality rate. Treatment failure may also be due to antibiotic tolerance. Accumulating evidence suggests that t the host immune environment plays an important role in inducing antibiotic tolerance of , but research in this area has been limited.
In this study,the minimum inhibitory concentration (MIC) of the antibiotics against was determined using the standard broth microdilution method.The study evaluated whether itaconate induces antibiotic tolerance in through an antibiotic bactericidal activity assay.The effect of itaconate on the growth of was evaluated by monitoring the growth of in medium supplemented with itaconate. Additionally, RNA sequencing and metabolomics analyses were used to determine transcriptional and metabolic changes in when exposed to itaconate.
According to the study,we found that the immune metabolite itaconate can induce tolerance in both methicillin-resistant and -susceptible to aminoglycosides. When was exposed to itaconate, its growth slowed down and transcriptomic and metabolomic alterations associated with decreased energy metabolism, including the tricarboxylate cycle, glycolysis, pyruvate metabolism, and arginine biosynthesis, were observed. These changes are associated with aminoglycoside tolerance. This study highlights the role of immune signaling metabolites in bacterial antibiotic tolerance and suggests new strategies to improve antibiotic treatment by modulating the host immune response and stimulating the metabolism of bacteria.
是导致慢性和复发性感染的主要病原体之一。抗生素无法抑制感染会导致复发，这是高死亡率的一个重要原因。治疗失败也可能是由于抗生素耐受性。越来越多的证据表明，宿主免疫环境在诱导的抗生素耐受性中起重要作用，但该领域的研究一直有限。
在本研究中，使用标准肉汤微量稀释法测定抗生素对的最低抑菌浓度（MIC）。该研究通过抗生素杀菌活性试验评估衣康酸是否诱导中的抗生素耐受性。通过监测在补充有衣康酸的培养基中的生长来评估衣康酸对生长的影响。此外，RNA测序和代谢组学分析用于确定暴露于衣康酸时中的转录和代谢变化。
根据该研究，我们发现免疫代谢物衣康酸可诱导耐甲氧西林和对氨基糖苷敏感的产生耐受性。当暴露于衣康酸时，其生长减慢，并观察到与能量代谢降低相关的转录组和代谢组改变，包括三羧酸循环、糖酵解、丙酮酸代谢和精氨酸生物合成。这些变化与氨基糖苷耐受性相关。本研究强调了免疫信号代谢物在细菌抗生素耐受性中的作用，并提出了通过调节宿主免疫反应和刺激细菌代谢来改善抗生素治疗的新策略。
