The wide utilization of
biocides poses a concern on the impact of these compounds on natural bacterial populations. Furthermore, it has been demonstrated that
biocides can select, at least in laboratory experiments,
antibiotic resistant bacteria. This situation has raised concerns, not just on scientists and clinicians, but also on regulatory agencies, which are demanding studies on the impact that the utilization of
biocides may have on the development on resistance and consequently on the treatment of
infectious diseases and on human health. In the present article, we explored the possibility that the widely used
biocide triclosan might induce antibiotic resistance using as a model the opportunistic pathogen Stenotrophomonas maltophilia. Biochemical, functional and structural studies were performed, focusing on SmeDEF, the most relevant
antibiotic- and
triclosan-removing multidrug efflux pump of S. maltophilia. Expression of smeDEF is regulated by the repressor SmeT.
Triclosan released SmeT from its operator and induces the expression of smeDEF, thus reducing the susceptibility of S. maltophilia to
antibiotics in the presence of the
biocide. The structure of SmeT bound to
triclosan is described. Two molecules of
triclosan were found to bind to one subunit of the SmeT homodimer. The binding of the
biocide stabilizes the N terminal domain of both subunits in a conformation unable to bind
DNA. To our knowledge this is the first crystal structure obtained for a transcriptional regulator bound to
triclosan. This work provides the molecular basis for understanding the mechanisms allowing the induction of phenotypic resistance to
antibiotics by
triclosan.