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Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility

BACKGROUND: Tigecycline resistance in Acinetobacter baumannii is primarily acquired through overexpression of the AdeABC efflux pump. Besides AdeRS, other two-component regulatory systems (TCSs) involving the regulation of this transporter have not been clarified. RESULTS: In this study, we found th...

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Autores principales: Lin, Ming-Feng, Lin, Yun-You, Yeh, Hui-Wen, Lan, Chung-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101873/
https://www.ncbi.nlm.nih.gov/pubmed/24885279
http://dx.doi.org/10.1186/1471-2180-14-119
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author Lin, Ming-Feng
Lin, Yun-You
Yeh, Hui-Wen
Lan, Chung-Yu
author_facet Lin, Ming-Feng
Lin, Yun-You
Yeh, Hui-Wen
Lan, Chung-Yu
author_sort Lin, Ming-Feng
collection PubMed
description BACKGROUND: Tigecycline resistance in Acinetobacter baumannii is primarily acquired through overexpression of the AdeABC efflux pump. Besides AdeRS, other two-component regulatory systems (TCSs) involving the regulation of this transporter have not been clarified. RESULTS: In this study, we found that the TCS genes baeR and baeS are co-transcribed and function as stress responders under high osmotic conditions. The baeSR and adeAB genes showed increased transcription in both the laboratory-induced and clinical tigecycline-resistant strains compared with the wild-type strain. The deletion of baeR in the ATCC 17978 strain led to 67–73% and 68% reduction in adeA and adeB expression, respectively, with a resultant 2-fold decrease in the tigecycline minimal inhibition concentration (MIC). In contrast, the overexpression of baeR resulted in a doubled tigecycline MIC, with a more than 2-fold increase in adeA and adeB expression. The influence of baeR knockout on adeAB gene expression can also be observed in the laboratory-induced tigecycline-resistant strain. A time-kill assay showed that the baeR deletion mutant showed an approximate 1-log(10) reduction in colony forming units (CFUs) relative to the wild-type strain when the tigecycline concentration was 0.25 μg/mL throughout the assay period. The wild-type phenotype could be restored by trans-complementation with pWH1266-kan( r )-baeR. Increasing the tigecycline concentration to 0.5 μg/mL produced an even more marked 4.7-log(10) reduction in CFUs of the baeR deletion mutant at 8 h, while only a 2.1-log(10) reduction was observed for the wild-type strain. CONCLUSIONS: Taken together, these data show for the first time that the BaeSR TCS influences the tigecycline susceptibility of A. baumannii through the positive regulation of the resistance-nodulation-division efflux pump genes adeA and adeB.
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spelling pubmed-41018732014-07-18 Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility Lin, Ming-Feng Lin, Yun-You Yeh, Hui-Wen Lan, Chung-Yu BMC Microbiol Research Article BACKGROUND: Tigecycline resistance in Acinetobacter baumannii is primarily acquired through overexpression of the AdeABC efflux pump. Besides AdeRS, other two-component regulatory systems (TCSs) involving the regulation of this transporter have not been clarified. RESULTS: In this study, we found that the TCS genes baeR and baeS are co-transcribed and function as stress responders under high osmotic conditions. The baeSR and adeAB genes showed increased transcription in both the laboratory-induced and clinical tigecycline-resistant strains compared with the wild-type strain. The deletion of baeR in the ATCC 17978 strain led to 67–73% and 68% reduction in adeA and adeB expression, respectively, with a resultant 2-fold decrease in the tigecycline minimal inhibition concentration (MIC). In contrast, the overexpression of baeR resulted in a doubled tigecycline MIC, with a more than 2-fold increase in adeA and adeB expression. The influence of baeR knockout on adeAB gene expression can also be observed in the laboratory-induced tigecycline-resistant strain. A time-kill assay showed that the baeR deletion mutant showed an approximate 1-log(10) reduction in colony forming units (CFUs) relative to the wild-type strain when the tigecycline concentration was 0.25 μg/mL throughout the assay period. The wild-type phenotype could be restored by trans-complementation with pWH1266-kan( r )-baeR. Increasing the tigecycline concentration to 0.5 μg/mL produced an even more marked 4.7-log(10) reduction in CFUs of the baeR deletion mutant at 8 h, while only a 2.1-log(10) reduction was observed for the wild-type strain. CONCLUSIONS: Taken together, these data show for the first time that the BaeSR TCS influences the tigecycline susceptibility of A. baumannii through the positive regulation of the resistance-nodulation-division efflux pump genes adeA and adeB. BioMed Central 2014-05-09 /pmc/articles/PMC4101873/ /pubmed/24885279 http://dx.doi.org/10.1186/1471-2180-14-119 Text en Copyright © 2014 Lin et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Lin, Ming-Feng
Lin, Yun-You
Yeh, Hui-Wen
Lan, Chung-Yu
Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility
title Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility
title_full Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility
title_fullStr Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility
title_full_unstemmed Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility
title_short Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility
title_sort role of the baesr two-component system in the regulation of acinetobacter baumannii adeab genes and its correlation with tigecycline susceptibility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101873/
https://www.ncbi.nlm.nih.gov/pubmed/24885279
http://dx.doi.org/10.1186/1471-2180-14-119
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