Title Genome-Wide Enrichment Screening Reveals Multiple Targets and Resistance Genes for Triclosan in Escherichia coli
Author Byung Jo Yu1, Jung Ae Kim1, Hyun Mok Ju1, Soo-Kyung Choi1, Seung Jin Hwang2, Sungyoo Park2, EuiJoong Kim3, and Jae-Gu Pan1*
Address 1Systems and Synthetic Biology Research Center, Korea Research of Bioscience and Biotechnology (KRIBB), Daejeon 305-701, Republic of Korea, 2LG Household and Healthcare Ltd, Daejeon 305-343, Republic of Korea, 3GenoFocus Inc., Daejeon 305-500, Republic of Korea
Bibliography Journal of Microbiology, 50(5),785-791, 2012,
DOI
Key Words triclosan, multiple targets, genomic library, resistance, E. 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 antibioticlike 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, cellsurface 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.