Triclosan-induced genes Rv1686c-Rv1687c and Rv3161c are not involved in triclosan resistance in Mycobacterium tuberculosis.
Triclosan-induced genes Rv1686c-Rv1687c and Rv3161c are not involved in triclosan resistance in Mycobacterium tuberculosis.
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DOI：
10.1038/srep26221
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发表时间：
2016-05-19
影响因子：
4.6
通讯作者：
Gibert I
中科院分区：
文献类型：
--
作者：
Gomez A;Andreu N;Ferrer-Navarro M;Yero D;Gibert I
开发抗击结核分枝杆菌的新化疗方法的一个关键问题是了解耐药的潜在机制。以往的研究表明，编码ATP结合盒转运蛋白和双加氧酶的基因Rv1686c-Rv1687c和Rv3161c分别在三氯生和其他抗菌化合物的存在下被诱导。因此，尽管还没有进行功能研究，但这些基因的产物在耐药中可能起到了作用。本研究的目的是阐明Rv1686c-Rv1687c和Rv3161c在结核分枝杆菌对三氯生和其他药物耐药中的作用。为此，构建了两个系统的缺陷突变株和高产菌株，并评估了它们对包括三氯生在内的20多种化合物的最低抑菌浓度(MIC)。出乎意料的是，在测试的任何化合物中，这些菌株的MIC与野生型H37Rv之间都没有观察到差异。此外，与Rv1686c-Rv1687c编码的转运蛋白类似，外排泵抑制剂也不影响三氯生的MIC。这些结果表明，这两个系统中的任何一个都不直接与结核分枝杆菌对三氯生或所测试的任何抗菌药的耐药性有关。
A key issue towards developing new chemotherapeutic approaches to fight Mycobacterium tuberculosis is to understand the mechanisms underlying drug resistance. Previous studies have shown that genes Rv1686c-Rv1687c and Rv3161c, predicted to encode an ATP-binding cassette transporter and a dioxygenase respectively, are induced in the presence of triclosan and other antimicrobial compounds. Therefore a possible role in drug resistance has been suggested for the products of these genes although no functional studies have been done. The aim of the present study was to clarify the role of Rv1686c-Rv1687c and Rv3161c in M. tuberculosis resistance to triclosan and other drugs. To this end, deficient mutants and overproducing strains for both systems were constructed and their minimal inhibitory concentration (MIC) against over 20 compounds, including triclosan, was evaluated. Unexpectedly, no differences between the MIC of these strains and the wild-type H37Rv were observed for any of the compounds tested. Moreover the MIC of triclosan was not affected by efflux pump inhibitors that inhibit the activity of transporters similar to the one encoded by Rv1686c-Rv1687c. These results suggest that none of the two systems is directly involved in M. tuberculosis resistance to triclosan or to any of the antimicrobials tested.