HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

The binding of triclosan to SmeT, the repressor of the multidrug efflux pump SmeDEF, induces antibiotic resistance in Stenotrophomonas maltophilia.

Abstract
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.
AuthorsAlvaro Hernández, Federico M Ruiz, Antonio Romero, José L Martínez
JournalPLoS pathogens (PLoS Pathog) Vol. 7 Issue 6 Pg. e1002103 (Jun 2011) ISSN: 1553-7374 [Electronic] United States
PMID21738470 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bacterial Proteins
  • Membrane Transport Proteins
  • Trans-Activators
  • Triclosan
Topics
  • Bacterial Proteins (chemistry, metabolism)
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Resistance, Bacterial
  • Membrane Transport Proteins (chemistry, metabolism)
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stenotrophomonas maltophilia (chemistry, drug effects, metabolism)
  • Trans-Activators (metabolism)
  • Transcription, Genetic
  • Triclosan (metabolism, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: