Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility.
Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility.
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DOI：
10.1186/1471-2180-14-119
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发表时间：
2014-05-09
期刊：
影响因子：
4.2
通讯作者：
Lan CY
中科院分区：
文献类型：
--
作者：
Lin MF;Lin YY;Yeh HW;Lan CY
鲍曼不动杆菌对替加环素的耐药性主要是通过AdeABC外排泵的过表达获得的。除ader外，其他涉及该转运体调控的双组分调控系统（TCSs）尚未明确。在这项研究中，我们发现TCS基因baeR和baeS是共转录的，并在高渗透条件下起应激反应作用。与野生型菌株相比，实验室诱导和临床耐替加环素菌株的baeSR和adeAB基因转录均增加。在ATCC 17978菌株中，baeR的缺失导致adeA和adeB的表达分别降低67-73%和68%，从而导致替加环素最小抑制浓度（MIC）降低2倍。相比之下，baeR过表达导致替加环素MIC增加一倍，adeA和adeB表达增加2倍以上。在实验室诱导的替加环素耐药菌株中，也可以观察到baeR敲除对adeAB基因表达的影响。时间杀伤实验表明，当替加环素浓度为0.25 μg/mL时，baeR缺失突变体的菌落形成单位（cfu）相对于野生型菌株减少了约1 log10。通过与pWH1266-kan r -baeR的反式互补可以恢复野生型表型。将替加环素浓度增加到0.5 μg/mL， baeR缺失突变株的cfu在8 h时下降了4.7 log10，而野生型菌株的cfu仅下降了2.1 log10。综上所述，这些数据首次表明BaeSR TCS通过正调控抗结核分裂外排泵基因adeA和adeB影响鲍曼不动杆菌对替加环素的敏感性。
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. 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-kan r -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. 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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影响因子：
3.7
作者：
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作者：
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影响因子：
5.2
作者：
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