title: Broad spectrum antimicrobial biocides target the FabI component of fatty acid synthesis.
abstract: The broad spectrum antibacterial properties of 2-hydroxydiphenyl ethers have been appreciated for decades, and their use in consumer products is rapidly increasing. We identify the enoyl-acyl carrier protein reductase (fabI) component of the type II fatty acid synthase system as the specific cellular target for these antibacterials. Biologically active 2-hydroxydiphenyl ethers effectively inhibit fatty acid synthesis in vivo and FabI activity in vitro. Resistant mechanisms include up-regulation of fabI expression and spontaneously arising missense mutations in the fabI gene. These results contradict the view that these compounds directly disrupt membranes and suggest that their widespread use will select for resistant bacterial populations.
authors.affiliation: Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Heath
authors.forename: Y T
authors.initials: YT
authors.lastname: Yu
authors.forename: M A
authors.initials: MA
authors.lastname: Shapiro
authors.forename: E
authors.initials: E
authors.lastname: Olson
authors.forename: C O
authors.initials: CO
authors.lastname: Rock
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D002417:Cattle; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D064429:Fatty Acid Synthases / Q000378:metabolism*; D066298:In Vitro Techniques; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics; D010636:Phenols / Q000494:pharmacology; D014260:Triclosan / Q000494:pharmacology
chemical_list: D000891:Anti-Infective Agents, Local; D010636:Phenols; D014260:Triclosan; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D064429:Fatty Acid Synthases; C038764:2,2'-biphenol