Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses

Burkholderia cepacia is an opportunistic pathogen that infects patients with debilitating underlying diseases. This study investigated the production of outer membrane vesicles (OMVs) by B. cepacia cultured with sub-minimum inhibitory concentrations (MICs) of antibiotics and examined their pathogeni...

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Main Authors: Se Yeon Kim, Mi Hyun Kim, Joo Hee Son, Seung Il Kim, Sung Ho Yun, Kyeongmin Kim, Shukho Kim, Minsang Shin, Je Chul Lee
Format: Article
Language:English
Published: Taylor & Francis Group 2020-12-01
Series:Virulence
Subjects:
Online Access:http://dx.doi.org/10.1080/21505594.2020.1802193
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author Se Yeon Kim
Mi Hyun Kim
Joo Hee Son
Seung Il Kim
Sung Ho Yun
Kyeongmin Kim
Shukho Kim
Minsang Shin
Je Chul Lee
author_facet Se Yeon Kim
Mi Hyun Kim
Joo Hee Son
Seung Il Kim
Sung Ho Yun
Kyeongmin Kim
Shukho Kim
Minsang Shin
Je Chul Lee
author_sort Se Yeon Kim
collection DOAJ
description Burkholderia cepacia is an opportunistic pathogen that infects patients with debilitating underlying diseases. This study investigated the production of outer membrane vesicles (OMVs) by B. cepacia cultured with sub-minimum inhibitory concentrations (MICs) of antibiotics and examined their pathogenic roles both in vitro and in vivo. B. cepacia ATCC 25416 produced more OMVs under antibiotic stress conditions than controls. OMVs isolated from B. cepacia cultured in Luria-Bertani (LB) broth (OMVs/LB) induced cytotoxicity and the expression of pro-inflammatory cytokine genes in A549 cells in a dose-dependent manner. Host cell cytotoxicity and pro-inflammatory responses were significantly higher in A549 cells treated with B. cepacia OMVs cultured with 1/4 MIC of ceftazidime (OMVs/CAZ) than in the cells treated with OMVs/LB, OMVs cultured with 1/4 MIC of trimethoprim/sulfamethoxazole (OMVs/SXT), or OMVs cultured with 1/4 MIC of meropenem. Intratracheal injection of B. cepacia OMVs also induced histopathology in vivo in mouse lungs. Expressions of IL-1β and TNF-α genes were significantly up-regulatedin the lungs of mice treated with OMVs/CAZ compared to mice administered other OMVs; the expression of the GRO-α gene, however, was significantly up-regulated in OMVs/SXT. In conclusion, OMVs produced by B. cepacia under different antibiotic stress conditions induce different host responses that may contribute to the pathogenesis of B. cepacia.
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spelling doaj.art-1b9073f84fcf45e48bc1f7bdd1e831ac2022-12-21T18:42:56ZengTaylor & Francis GroupVirulence2150-55942150-56082020-12-01111995100510.1080/21505594.2020.18021931802193Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responsesSe Yeon Kim0Mi Hyun Kim1Joo Hee Son2Seung Il Kim3Sung Ho Yun4Kyeongmin Kim5Shukho Kim6Minsang Shin7Je Chul Lee8School of Medicine, Kyungpook National UniversitySchool of Medicine, Kyungpook National UniversitySchool of Medicine, Kyungpook National UniversityKorea Basic Science InstituteKorea Basic Science InstituteSchool of Medicine, Kyungpook National UniversitySchool of Medicine, Kyungpook National UniversitySchool of Medicine, Kyungpook National UniversitySchool of Medicine, Kyungpook National UniversityBurkholderia cepacia is an opportunistic pathogen that infects patients with debilitating underlying diseases. This study investigated the production of outer membrane vesicles (OMVs) by B. cepacia cultured with sub-minimum inhibitory concentrations (MICs) of antibiotics and examined their pathogenic roles both in vitro and in vivo. B. cepacia ATCC 25416 produced more OMVs under antibiotic stress conditions than controls. OMVs isolated from B. cepacia cultured in Luria-Bertani (LB) broth (OMVs/LB) induced cytotoxicity and the expression of pro-inflammatory cytokine genes in A549 cells in a dose-dependent manner. Host cell cytotoxicity and pro-inflammatory responses were significantly higher in A549 cells treated with B. cepacia OMVs cultured with 1/4 MIC of ceftazidime (OMVs/CAZ) than in the cells treated with OMVs/LB, OMVs cultured with 1/4 MIC of trimethoprim/sulfamethoxazole (OMVs/SXT), or OMVs cultured with 1/4 MIC of meropenem. Intratracheal injection of B. cepacia OMVs also induced histopathology in vivo in mouse lungs. Expressions of IL-1β and TNF-α genes were significantly up-regulatedin the lungs of mice treated with OMVs/CAZ compared to mice administered other OMVs; the expression of the GRO-α gene, however, was significantly up-regulated in OMVs/SXT. In conclusion, OMVs produced by B. cepacia under different antibiotic stress conditions induce different host responses that may contribute to the pathogenesis of B. cepacia.http://dx.doi.org/10.1080/21505594.2020.1802193burkholderia cepaciaantibioticsouter membrane vesiclecytotoxicityinflammatory response
spellingShingle Se Yeon Kim
Mi Hyun Kim
Joo Hee Son
Seung Il Kim
Sung Ho Yun
Kyeongmin Kim
Shukho Kim
Minsang Shin
Je Chul Lee
Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses
Virulence
burkholderia cepacia
antibiotics
outer membrane vesicle
cytotoxicity
inflammatory response
title Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses
title_full Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses
title_fullStr Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses
title_full_unstemmed Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses
title_short Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses
title_sort outer membrane vesicles produced by burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro inflammatory responses
topic burkholderia cepacia
antibiotics
outer membrane vesicle
cytotoxicity
inflammatory response
url http://dx.doi.org/10.1080/21505594.2020.1802193
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