Differential proteomic analysis and pathogenic effects of outer membrane vesicles derived from Acinetobacter baumannii under normoxia and hypoxia

PLoS One. 2023 Mar 15;18(3):e0283109. doi: 10.1371/journal.pone.0283109. eCollection 2023.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections* / microbiology
  • Acinetobacter baumannii*
  • Animals
  • Bacterial Outer Membrane Proteins / metabolism
  • Humans
  • Hypoxia / metabolism
  • Mice
  • Proteomics
  • Secretory Vesicles / metabolism

Substances

  • Bacterial Outer Membrane Proteins

Grants and funding

This study was supported by Japan Society for the Promotion of Science KAKENHI Grant Number 22K15454 (P. Subsomwong), Research Grant from Ichimaru Pharcos Co. Ltd. (531021K019) (A. Nakane), and a grant from the 35th Karoji Memorial Fund for Medical Research (Grant A, 2016) (K. Asano). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.