Antibiotic Treatment Modulates Protein Components of Cytotoxic Outer Membrane Vesicles of Multidrug-resistant Clinical Strain, DU202
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Background: Outer membrane vesicles (OMVs) of are cytotoxic and elicit a potent innate immune response. OMVs were first identified in DU202, an extensively drug-resistant clinical strain. Herein, we investigated protein components of DU202 OMVs following antibiotic treatment by proteogenomic analysis.
Methods: Purified OMVs from 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.
Results: OMV 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.
Conclusion: In vitro stress such as antibiotic treatment can modulate proteome components in OMVs and thereby influence pathogenicity.
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