Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
PLoS One. 2023 Mar 15;18(3):e0283109. doi: 10.1371/journal.pone.0283109. eCollection 2023.
Acinetobacter baumannii is a major causative agent of nosocomial infections and its outer membrane vesicles (AbOMVs) have been shown to be involved in pathogenicity by transporting virulence factors and transferring information for communication between pathogens and host cells. Despite the fact that the infected sites of A. baumannii such as lungs and skin soft tissues are hypoxic, most studies on AbOMV virulence have used AbOMVs prepared under aerobic conditions. The present study aims to elucidate the protein profile and pathogenic impact of AbOMVs released under hypoxic condition. AbOMVs were isolated from A. baumannii under normoxic and hypoxic conditions, and their protein profiles were compared. The different effects of both normoxic and hypoxic AbOMVs in cytokine response from mouse macrophages, cytotoxicity to the human lung epithelial cells, and bacterial invasion were then investigated. Our results showed that A. baumannii under hypoxia released larger amounts of OMVs with different protein profiles. Although the cytotoxic effect of AbOMVs from normoxia and hypoxia were comparable, AbOMVs from normoxia induced higher TNF-α production and invasion of Staphylococcus aureus and Pseudomonas aeruginosa than those from hypoxia. On the other hand, AbOMVs significantly enhanced A. baumannii invasion into lung epithelial cells in a dose-dependent manner. These results clearly demonstrate that AbOMVs released from normoxic and hypoxic have different impacts in pathogenesis. This finding provides new insight into the complex interactions between A. baumannii, coinfecting pathogens and host cells via OMVs, in particular the different pathogenic effects of AbOMVs under normoxic and hypoxic conditions.
鲍曼不动杆菌是医院感染的主要病原体，其外膜囊泡（AbOMVs）被证明通过运输毒力因子和传递病原体与宿主细胞之间的信息而参与致病作用。尽管鲍曼不动杆菌感染的部位，如肺部和皮肤软组织是缺氧的，但大多数关于 AbOMV 毒力的研究都是使用在有氧条件下制备的 AbOMVs 进行的。本研究旨在阐明在缺氧条件下释放的 AbOMV 的蛋白质谱和致病作用。从有氧和缺氧条件下的鲍曼不动杆菌中分离 AbOMV，并比较其蛋白质谱。然后研究了正常氧和缺氧 AbOMV 在小鼠巨噬细胞细胞因子反应、对人肺上皮细胞的细胞毒性和细菌侵袭方面的不同影响。我们的结果表明，缺氧下的鲍曼不动杆菌释放了具有不同蛋白质谱的大量 OMVs。尽管正常氧和缺氧 AbOMV 的细胞毒性相当，但正常氧 AbOMV 诱导的 TNF-α产生和金黄色葡萄球菌和铜绿假单胞菌的侵袭比缺氧 AbOMV 更高。另一方面，AbOMV 显著增强了鲍曼不动杆菌以剂量依赖的方式侵入肺上皮细胞。这些结果清楚地表明，正常氧和缺氧释放的 AbOMV 在发病机制中具有不同的影响。这一发现为鲍曼不动杆菌、共感染病原体和宿主细胞通过 OMV 之间的复杂相互作用提供了新的见解，特别是 AbOMV 在正常氧和缺氧条件下的不同致病作用。
