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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Pseudomonas aeruginosa-induced mitochondrial dysfunction inhibits proinflammatory cytokine secretion and enhances cytotoxicity in mouse macrophages in a reactive oxygen species (ROS)-dependent way

Abstract: Pseudomonas aeruginosa belongs to the genus Pseudomonas and is a common Gram-negative, exclusively aerobic, conditionally pathogenic bacterium with the characteristics of easy colonization, mutation, and multidrug resistance (Deng et al., 2015; Azam and Khan, 2019; Jurado-Martn et al., 2021). It is mainly distributed in the air, soil, water, intestinal tract, and skin surface of humans and domestic animals and can cause complications such as ulcerative keratitis, otitis externa, skin and soft tissue infections, respiratory infections, sepsis, osteomyelitis, endocarditis, and urinary tract infections in burned or immunocompromised patients (Azam and Khan, 2019; Chai and Xu, 2020; Voth et al., 2020). P. aeruginosa is a naturally drug-resistant bacterium that is resistant to a wide range of antibiotics, making it one of the major opportunistic pathogens leading to in-hospital infections (Pang et al., 2019; Chai and Xu, 2020; Reynolds and Kollef, 2021). According to the surveillance report of the China Antimicrobial Resistance Surveillance System (CARSS, http://www.carss.cn), Gram-negative bacteria accounted for more than 70% of all bacterial infections, and P. aeruginosa accounted for 12.4%, 12.0%, and 12.2% in 2018, 2019, and 2020, respectively. Therefore, P. aeruginosa infection has become an important concern in public health care, and it is particularly important to gain insight into the means of host immune defense against P. aeruginosa infection.

Key words: Pseudomonas aeruginosa; Mitochondria; Mitophagy; Proinflammatory cytokines

Chinese Summary  <11> 铜绿假单胞菌诱导的线粒体功能障碍以ROS依赖性的方式抑制促炎细胞因子分泌并增强小鼠巨噬细胞的细胞毒性

杨海涛1,王彦2,樊慧1,刘飞雪1,冯会苗1,李雪晴1,储铭仪1,潘恩壮1,滕道阳1,陈慧珍3,董井泉1
1江苏海洋大学药学院,江苏省海洋生物资源与环境重点实验室,江苏省海洋生物产业技术协同创新中心,江苏省海洋药物化合物筛选重点实验室,中国连云港市,222005
2连云港市第二人民医院,南京医科大学康达学院附属连云港第二人民医院医学检验科,中国连云港市,222000
3连云港市第一人民医院神经科学研究所,中国连云港市,222000
摘要:随着铜绿假单胞菌(铜绿)的耐药性逐年增强,铜绿感染已经成为公共医疗卫生的重点关注问题。线粒体自噬及其介导的线粒体功能障碍在多种细菌感染中已被报道,但线粒体功能障碍在宿主调控铜绿感染中的作用尚不明确。因此,本研究建立铜绿刺激小鼠巨噬细胞感染模型和小鼠急性铜绿感染模型,探讨铜绿是否通过诱导线粒体自噬改变线粒体功能,进而影响宿主免疫炎症反应和细胞毒性,并通过监测生存率和肺组织病理学变化进一步确定线粒体自噬在小鼠铜绿体内感染模型中的作用。结果表明,铜绿引起小鼠腹腔巨噬细胞线粒体功能障碍,并通过线粒体自噬途径清除铜绿刺激引起的活性氧(ROS)累积,从而抑制铜绿引起的促炎性细胞因子分泌并增强细胞毒性。体内实验进一步确认线粒体自噬在铜绿体内感染中的作用。

关键词组:铜绿假单胞菌;线粒体;线粒体自噬;促炎性细胞因子


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DOI:

10.1631/jzus.B2300051

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On-line Access:

2023-11-14

Received:

2023-01-17

Revision Accepted:

2023-04-20

Crosschecked:

2023-11-15

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