Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

Sung Ho Yun,Hyun-Joo Ro,Sang-Yeop Lee,Hye-Yeon Kim,Sangmi Jun,Hayoung Lee,Gun-Hwa Kim,Edmond Changkyun Park,Je Chul Lee,Chi-Won Choi,Yoon-Sun Yi,Seung Il Kim

doi:10.1186/s12014-018-9204-2

Abstract

BackgroundOuter membrane vesicles (OMVs) of Acinetobacter baumannii are cytotoxic and elicit a potent innate immune response. OMVs were first identified in A. baumannii DU202, an extensively drug-resistant clinical strain. Herein, we investigated protein components of A. baumannii DU202 OMVs following antibiotic treatment by proteogenomic analysis.MethodsPurified OMVs from A. baumannii DU202 grown in different antibiotic culture conditions were screened for pathogenic and immunogenic effects, and subjected to quantitative proteomic analysis by one-dimensional electrophoresis and liquid chromatography combined with tandem mass spectrometry (1DE-LC-MS/MS). Protein components modulated by imipenem were identified and discussed.ResultsOMV secretion was increased > twofold following imipenem treatment, and cytotoxicity toward A549 human lung carcinoma cells was elevated. A total of 277 proteins were identified as components of OMVs by imipenem treatment, among which β-lactamase OXA-23, various proteases, outer membrane proteins, β-barrel assembly machine proteins, peptidyl-prolyl cis–trans isomerases and inherent prophage head subunit proteins were significantly upregulated.ConclusionIn vitro stress such as antibiotic treatment can modulate proteome components in A. baumannii OMVs and thereby influence pathogenicity.

Highlights

Acinetobacter baumannii is a major Gram-negative bacterial pathogen that causes nosocomial infections such as ventilator-associated pneumonia, bacteraemia and urinary tract infections [1]
We found that the production of A. baumannii DU202 Outer membrane vesicles (OMVs) was increased by imipenem treatment, and became more cytotoxic toward cultured host cells
We recently reported the complete genome of A. baumannii DU202 [16], and here we used this resource to perform proteogenomic analysis of protein components of OMVs following antibiotic treatment

Summary

Introduction

Acinetobacter baumannii is a major Gram-negative bacterial pathogen that causes nosocomial infections such as ventilator-associated pneumonia, bacteraemia and urinary tract infections [1]. Like most Gram-negative bacteria, A. baumannii secretes outer membrane vesicles (OMVs), as first demonstrated using the A. baumannii. DU202 multidrug-resistant (MDR) clinical strain that is cytotoxic and elicits a potent innate immune response in the host [2,3,4]. Vaccination of whole A. baumannii OMVs alone or in combination with biofilm-associated protein (Bap) effectively protects against A. baumannii infection and elevates innate immunity [5,6,7]. The plasmid-borne blaoxa-24 gene has been transferred into the carbapenemsusceptible A. baumannii ATCC 17978 strain using carbapenem-resistant A. baumannii OMVs as a vehicle for horizontal gene transfer [8]. Elucidation of the biological roles of the protein components of. Outer membrane vesicles (OMVs) of Acinetobacter baumannii are cytotoxic and elicit a potent innate immune response. We investigated protein components of A. baumannii DU202 OMVs following antibiotic treatment by proteog‐ enomic analysis

Methods

Results

Conclusion