Bacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem

Patients with Acinetobacter baumannii bacteremia treated with antipseudomonal cephalosporins showed higher 14-day mortality than patients treated with antipseudomonal carbapenems. We hypothesized that the bacterial membrane vesicles (BMVs) induced by antipseudomonal cephalosporins are more virulent...

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Autores principales: Chun-Hsiang Chiu, Yi-Tzu Lee, Yu-Chun Lin, Shu-Chen Kuo, Ya-Sung Yang, Yung-Chih Wang, Yu-Han Liu, Jung-Chung Lin, Feng-Yee Chang, Te-Li Chen
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Publicado: Taylor & Francis Group 2020
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Acceso en línea:https://doaj.org/article/719c766ad5054befbe957d4b7ad9fac0
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spelling oai:doaj.org-article:719c766ad5054befbe957d4b7ad9fac02021-11-17T14:21:57ZBacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem2150-55942150-560810.1080/21505594.2020.1726593https://doaj.org/article/719c766ad5054befbe957d4b7ad9fac02020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1726593https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Patients with Acinetobacter baumannii bacteremia treated with antipseudomonal cephalosporins showed higher 14-day mortality than patients treated with antipseudomonal carbapenems. We hypothesized that the bacterial membrane vesicles (BMVs) induced by antipseudomonal cephalosporins are more virulent than BMVs induced by antipseudomonal carbapenems. To simulate the clinical condition with inadequate antimicrobial treatment, carbapenem-resistant A. baumannii was treated with ceftazidime (an antipseudomonal cephalosporin) or imipenem (an antipseudomonal carbapenem) at 1/2 the minimum inhibitory concentration. BMVs and BMV-carried lipopolysaccharide were measured by nanoparticle tracking analysis and western blotting, respectively. Cytokine expression in RAW264.7 macrophages or mice serum induced by the BMVs was determined by ELISA, fluorescent bead-based immunoassay or western blotting. The virulence of the BMVs was assessed in mice. Liquid chromatography tandem-mass spectrometry was used to determine the protein contents of the BMVs. We found that ceftazidime induced a higher number of BMVs (CAZ-BMV), which carried more LPS, and induced higher expression levels of iNOS, IL-1β, and IL-6 in macrophages, higher expression of many cytokines in mice, more neutrophil infiltration in lung interstitium, and higher mortality in mice than imipenem-induced BMVs (IMP-BMV). When adjusted to same amount of LPS, CAZ-BMV still led to higher mortality than IMP-BMV. Proteomic analysis revealed different protein contents in CAZ-BMV and IMP-BMV. In conclusion, A. baumannii BMVs induced by ceftazidime are more virulent than BMVs induced by imipenem.Chun-Hsiang ChiuYi-Tzu LeeYu-Chun LinShu-Chen KuoYa-Sung YangYung-Chih WangYu-Han LiuJung-Chung LinFeng-Yee ChangTe-Li ChenTaylor & Francis Grouparticlebacterial membrane vesiclesacinetobacter baumanniiceftazidimeimipenemvirulenceInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 145-158 (2020)
institution DOAJ
collection DOAJ
language EN
topic bacterial membrane vesicles
acinetobacter baumannii
ceftazidime
imipenem
virulence
Infectious and parasitic diseases
RC109-216
spellingShingle bacterial membrane vesicles
acinetobacter baumannii
ceftazidime
imipenem
virulence
Infectious and parasitic diseases
RC109-216
Chun-Hsiang Chiu
Yi-Tzu Lee
Yu-Chun Lin
Shu-Chen Kuo
Ya-Sung Yang
Yung-Chih Wang
Yu-Han Liu
Jung-Chung Lin
Feng-Yee Chang
Te-Li Chen
Bacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem
description Patients with Acinetobacter baumannii bacteremia treated with antipseudomonal cephalosporins showed higher 14-day mortality than patients treated with antipseudomonal carbapenems. We hypothesized that the bacterial membrane vesicles (BMVs) induced by antipseudomonal cephalosporins are more virulent than BMVs induced by antipseudomonal carbapenems. To simulate the clinical condition with inadequate antimicrobial treatment, carbapenem-resistant A. baumannii was treated with ceftazidime (an antipseudomonal cephalosporin) or imipenem (an antipseudomonal carbapenem) at 1/2 the minimum inhibitory concentration. BMVs and BMV-carried lipopolysaccharide were measured by nanoparticle tracking analysis and western blotting, respectively. Cytokine expression in RAW264.7 macrophages or mice serum induced by the BMVs was determined by ELISA, fluorescent bead-based immunoassay or western blotting. The virulence of the BMVs was assessed in mice. Liquid chromatography tandem-mass spectrometry was used to determine the protein contents of the BMVs. We found that ceftazidime induced a higher number of BMVs (CAZ-BMV), which carried more LPS, and induced higher expression levels of iNOS, IL-1β, and IL-6 in macrophages, higher expression of many cytokines in mice, more neutrophil infiltration in lung interstitium, and higher mortality in mice than imipenem-induced BMVs (IMP-BMV). When adjusted to same amount of LPS, CAZ-BMV still led to higher mortality than IMP-BMV. Proteomic analysis revealed different protein contents in CAZ-BMV and IMP-BMV. In conclusion, A. baumannii BMVs induced by ceftazidime are more virulent than BMVs induced by imipenem.
format article
author Chun-Hsiang Chiu
Yi-Tzu Lee
Yu-Chun Lin
Shu-Chen Kuo
Ya-Sung Yang
Yung-Chih Wang
Yu-Han Liu
Jung-Chung Lin
Feng-Yee Chang
Te-Li Chen
author_facet Chun-Hsiang Chiu
Yi-Tzu Lee
Yu-Chun Lin
Shu-Chen Kuo
Ya-Sung Yang
Yung-Chih Wang
Yu-Han Liu
Jung-Chung Lin
Feng-Yee Chang
Te-Li Chen
author_sort Chun-Hsiang Chiu
title Bacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem
title_short Bacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem
title_full Bacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem
title_fullStr Bacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem
title_full_unstemmed Bacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem
title_sort bacterial membrane vesicles from acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem
publisher Taylor & Francis Group
publishDate 2020
url https://doaj.org/article/719c766ad5054befbe957d4b7ad9fac0
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