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Open Access Research article

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

Ming-Feng Lin12, Yun-You Lin1, Hui-Wen Yeh3 and Chung-Yu Lan24*

Author Affiliations

1 Department of Medicine, National Taiwan University Hospital Chu-Tung Branch, Hsin-Chu County, Taiwan

2 Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsin-Chu City, Taiwan

3 Laboratory Medicine Division, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan

4 Department of Life Science, National Tsing Hua University, Hsin-Chu City, Taiwan

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BMC Microbiology 2014, 14:119  doi:10.1186/1471-2180-14-119

Published: 9 May 2014

Abstract

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-log10 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-kanr-baeR. Increasing the tigecycline concentration to 0.5 μg/mL produced an even more marked 4.7-log10 reduction in CFUs of the baeR deletion mutant at 8 h, while only a 2.1-log10 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.

Keywords:
Acinetobacter baumannii; Tigecycline; Two-component regulatory system; Efflux pumps