title: Genome-wide enrichment screening reveals multiple targets and resistance genes for triclosan in Escherichia coli.
abstract: Triclosan is a widely used biocide effective against different microorganisms. At bactericidal concentrations, triclosan appears to affect multiple targets, while at bacteriostatic concentrations, triclosan targets FabI. The site-specific antibiotic-like mode-of-action and a widespread use of triclosan in household products claimed to possibly induce cross-resistance to other antibiotics. Thus, we set out to define more systematically the genes conferring resistance to triclosan; A genomic library of Escherichia coli strain W3110 was constructed and enriched in a selective medium containing a lethal concentration of triclosan. The genes enabling growth in the presence of triclosan were identified by using a DNA microarray and confirmed consequently by ASKA clones overexpressing the selected 62 candidate genes. Among these, forty-seven genes were further confirmed to enhance the resistance to triclosan; these genes, including the FabI target, were involved in inner or outer membrane synthesis, cell-surface material synthesis, transcriptional activation, sugar phosphotransferase (PTS) systems, various transporter systems, cell division, and ATPase and reductase/dehydrogenase reactions. In particular, overexpression of pgsA, rcsA, or gapC conferred to E. coli cells a similar level of triclosan resistance induced by fabI overexpression. These results indicate that triclosan may have multiple targets other than well-known FabI and that there are several undefined novel mechanisms for the resistance development to triclosan, thus probably inducing cross antibiotic resistance.
authors.affiliation: Systems and Synthetic Biology Research Center, Korea Research of Bioscience and Biotechnology (KRIBB), Daejeon 305-701, Republic of Korea.
authors.forename: Byung Jo
authors.initials: BJ
authors.lastname: Yu
authors.forename: Jung Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Hyun Mok
authors.initials: HM
authors.lastname: Ju
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Choi
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Sungyoo
authors.initials: S
authors.lastname: Park
authors.forename: Euijoong
authors.initials: E
authors.lastname: Kim
authors.forename: Jae-Gu
authors.initials: JG
authors.lastname: Pan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D016680:Genome, Bacterial; D014260:Triclosan / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D014260:Triclosan