Differential proteomic analysis and pathogenic effects of outer membrane vesicles derived from Acinetobacter
Sachio Suzuki1, Phawinee Subsomwong2, Kouji Narita2,3
1Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
Abstract:
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.
Insights
Acinetobacter baumannii outer membrane vesicles (AbOMVs) differ in protein content and pathogenic effects depending on oxygen levels. Hypoxic AbOMVs show distinct impacts on host cells and coinfecting bacteria compared to aerobic ones.
Area of Science:
- Microbiology
- Pathogenesis
- Extracellular Vesicles
Background:
- Acinetobacter baumannii causes significant nosocomial infections.
- Outer membrane vesicles (AbOMVs) mediate virulence and inter-pathogen communication.
- Infected sites are often hypoxic, yet AbOMV studies typically use aerobic conditions.
Purpose of the Study:
- To investigate the protein profiles of AbOMVs under normoxic and hypoxic conditions.
- To compare the pathogenic impacts of normoxic and hypoxic AbOMVs on host cells and coinfecting bacteria.
Main Methods:
- Isolation of AbOMVs from A. baumannii under normoxic and hypoxic conditions.
- Comparative analysis of AbOMV protein profiles.
- Assessment of cytokine response, cytotoxicity, and bacterial invasion.
Main Results:
- Hypoxia induced larger AbOMV release with altered protein profiles.
- Cytotoxicity was similar, but normoxic AbOMVs induced higher TNF-α and enhanced invasion of coinfecting bacteria.
- AbOMVs significantly increased A. baumannii invasion into lung cells.
Conclusions:
- AbOMVs exhibit distinct pathogenic effects under normoxic and hypoxic conditions.
- Oxygen levels influence AbOMV composition and virulence.
- Findings offer insights into A. baumannii pathogenesis and interactions with host cells and coinfecting pathogens.
