Triclosan-induced genes Rv1686c-Rv1687c and Rv3161c are not involved in triclosan resistance in Mycobacterium tuberculosis

摘要

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.