Inactivation of a novel three-cistronic operon tcaR-tcaA-tcaB increases teicoplanin resistance in Staphylococcus aureus

Inactivation of a novel three-cistronic operon tcaR-tcaA-tcaB increases teicoplanin resistance in Staphylococcus aureus
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DOI:
10.1016/s0304-4165(00)00133-1
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发表时间:
2000-10-18
影响因子:
3
通讯作者:
Berger-Bächi, B
Berger-Bächi, B
中科院分区:
生物学3区
文献类型:
--
作者:
Brandenberger, M;Tschierske, M;Berger-Bächi, B

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通过Tn 917介导的插入突变鉴定了一种新的替考拉宁相关操纵子,称为tcaR-tcaA-tcaB。通过tcaA插入失活或缺失整个操纵子,替考拉宁耐药性增加4倍。tcaA编码一种假设的跨膜蛋白,具有金属结合基序,可能是传感器-换能器。tcaB编码膜相关蛋白,其与双环霉素抗性蛋白具有序列同源性。这两个基因之前是tcaR,其编码与转录调节因子马尔R具有序列同源性的推定调节因子。tcaA失活和tcaRAB缺失导致替考拉宁耐药增加的事实相同,证实了tcaRAB与替考拉宁敏感性相关。共转导杂交表明,这些插入产生的替考拉宁耐药水平具有菌株依赖性,在甲氧西林耐药菌株COL中,它与甲氧西林耐药显著降低配对。这允许假设tcaRAB可能以某种方式参与细胞壁生物合成,替考拉宁可能直接或间接与TcaA和/或TcaB相互作用。(C)2000 Elsevier Science B. V.保留所有权利。
A novel teicoplanin-associated operon termed tcaR-tcaA-tcaB was identified by Tn917-mediated insertional mutagenesis. Resistance to teicoplanin rose 4-fold by insertional inactivation of tcaA or by deletion of the entire operon. tcaA encodes a hypothetical transmembrane protein with a metal-binding motif, possibly a sensor-transducer. tcaB codes for a membrane-associated protein, which has sequence homologies to a bicyclomycin resistance protein. The two genes are preceded by tcaR encoding a putative regulator with sequence homologies to the transcriptional regulator MarR. The fact that tcaA inactivation as well as deletion of tcaRAB produced the same increase in teicoplanin resistance confirmed the association of tcaRAB with teicoplanin susceptibility. Cotransductional crosses showed that the level of teicoplanin resistance produced by these insertions was strain-dependent and that in the methicillin-resistant strain COL, it was paired with a remarkable decrease in methicillin resistance. This allowed to postulate that tcaRAB may be involved in some way in cell wall biosynthesis, and that teicoplanin may interact with TcaA and/or TcaB either directly or indirectly. (C) 2000 Elsevier Science B.V. All rights reserved.