title: Biochemical and genetic characterization of the action of triclosan on Staphylococcus aureus.
abstract: Triclosan, a widely used antibacterial agent, possesses potent activity against Staphylococcus aureus. This study reports on an investigation of the antibacterial target of triclosan in this pathogen. A strain of S. aureus overexpressing the enoyl-[acyl-carrier-protein] reductase (FabI), demonstrated by Western immunoblotting, gave rise to an increase in the MIC of triclosan, while susceptibilities to a range of unrelated antibacterials were unaffected. There are approximately 12 000 molecules of FabI per cell in mid-log phase growth. This number increased by approximately three- to four-fold in the S. aureus FabI overexpressor. Triclosan selectively inhibited the incorporation of [(14)C]acetate into TCA-precipitable product, an indicator of fatty acid biosynthesis. Furthermore, it inhibited de novo fatty acid biosynthesis in this organism. In vitro, triclosan inhibited recombinant, purified S. aureus FabI with an IC(50) of approximately 1 microM. The combination of these biochemical and genetic data provide further evidence that the mode of action of triclosan in S. aureus is via inhibition of FabI.
authors: Anti-Infectives Research, GlaxoSmithKline Pharmaceuticals, 1250 S. Collegeville Road, Collegeville, PA 19426, USA.
authors: C
authors: C
authors: Slater-Radosti
authors: G
authors: G
authors: Van Aller
authors: R
authors: R
authors: Greenwood
authors: R
authors: R
authors: Nicholas
authors: P M
authors: PM
authors: Keller
authors: W E
authors: WE
authors: DeWolf
authors: F
authors: F
authors: Fan
authors: D J
authors: DJ
authors: Payne
authors: D D
authors: DD
authors: Jaworski
mesh_terms: D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014260:Triclosan / Q000494:pharmacology*
chemical_list: D000891:Anti-Infective Agents, Local; D014260:Triclosan