Wang Bu, Zhang Wei, Liu Jianhua, Zhang Hongxia, Li Maochen, Peng Xiaocui, Zhang Zhihua, Song Ning
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei Northern University Zhangjiakou, Hebei, P.R. China.
Department of Microbiology, The First Affiliated Hospital of Hebei North University Zhangjiakou, Hebei, P.R. China.
Am J Transl Res. 2025 Aug 15;17(8):6103-6112. doi: 10.62347/QVUY9908. eCollection 2025.
This study aimed to investigate the roles and mechanisms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the drug resistance of , focusing on its regulation of the aminoglycoside resistance methylase (armA) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.
A549 cells were infected with drug-resistant and treated with meropenem. TRAIL overexpression and knockdown were performed using plasmids and small interfering RNA, respectively. Cell viability, apoptosis, and the levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were assessed. The mRNA expression of armA was examined using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The expression of key proteins in the PI3K/AKT/mTOR pathway was evaluated using western blots.
Drug-resistant infection reduced A549 cell viability, promoted apoptosis, and increased TNF-α, IL-6, and IL-1β levels. Meropenem treatment failed to reverse these effects, confirming the drug resistance. TRAIL overexpression exacerbated infection-induced viability inhibition, apoptosis, and inflammation, suggesting that TRAIL enhances the drug resistance of . In contrast, TRAIL knockdown showed the opposite results. TRAIL overexpression upregulated armA expression and activated the PI3K/AKT/mTOR pathway, but armA inhibition reversed TRAIL-mediated drug resistance and PI3K/AKT/mTOR activation.
TRAIL-mediated armA upregulation enhanced the drug resistance of by activating the PI3K/AKT/mTOR signaling pathway. These findings provide new insight into the drug resistance mechanisms of .
本研究旨在探讨肿瘤坏死因子相关凋亡诱导配体（TRAIL）在[具体研究对象]耐药中的作用及机制，重点关注其对氨基糖苷类耐药甲基化酶（armA）和磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素哺乳动物靶蛋白（mTOR）信号通路的调控。
用耐药的[具体病原体]感染A549细胞并用美罗培南处理。分别使用质粒和小干扰RNA进行TRAIL过表达和敲低。评估细胞活力、凋亡以及包括肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）在内的炎性细胞因子水平。使用逆转录定量聚合酶链反应（RT-qPCR）检测armA的mRNA表达。使用蛋白质免疫印迹法评估PI3K/AKT/mTOR通路中关键蛋白的表达。
耐药的[具体病原体]感染降低了A549细胞活力，促进了凋亡，并增加了TNF-α、IL-6和IL-1β水平。美罗培南处理未能逆转这些效应，证实了耐药性。TRAIL过表达加剧了[具体病原体]感染诱导的活力抑制、凋亡和炎症，表明TRAIL增强了[具体病原体]的耐药性。相反，TRAIL敲低显示出相反的结果。TRAIL过表达上调了armA表达并激活了PI3K/AKT/mTOR通路，但armA抑制逆转了TRAIL介导的耐药性和PI3K/AKT/mTOR激活。
TRAIL介导的armA上调通过激活PI3K/AKT/mTOR信号通路增强了[具体病原体]的耐药性。这些发现为[具体病原体]的耐药机制提供了新的见解。
