Genome-Wide Enrichment Screening Reveals Multiple Targets and Resistance Genes for Triclosan in Escherichia coli

• Published in: The journal of microbiology Vol. 50; no. 5; pp. 785 - 791
• Main Authors: Yu, B.J., Systems and Synthetic Biology Research Center, KRIBB, Daejeon, Republic of Korea, Kim, J.A., Systems and Synthetic Biology Research Center, KRIBB, Daejeon, Republic of Korea, Ju, H.M., Systems and Synthetic Biology Research Center, KRIBB, Daejeon, Republic of Korea, Choi, S.K., Systems and Synthetic Biology Research Center, KRIBB, Daejeon, Republic of Korea, Hwang, S.J., LG Household and Healthcare Ltd., Daejeon, Republic of Korea, Park, S.Y., LG Household and Healthcare Ltd., Daejeon, Republic of Korea, Kim, E.J., GenoFocus Inc., Daejeon, Republic of Korea, Pan, J.G., Systems and Synthetic Biology Research Center, KRIBB, Daejeon, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Heidelberg The Microbiological Society of Korea 01.10.2012; Springer Nature B.V; 한국미생물학회
• Subjects: Adenosinetriphosphatase; Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Biocides; Biomedical and Life Sciences; Cell division; clones; Cloning; Cross-resistance; dehydrogenase; Dehydrogenases; DNA microarrays; drug effects; Drug Resistance, Bacterial; E coli; Enzymes; ESCHERICHIA COLI; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; gene overexpression; genes; genetic resistance; genetics; Genome, Bacterial; Genomes; genomic libraries; genomic library; Genomics; Household products; Hybridization; induced resistance; Kinases; Life Sciences; mechanism of action; metabolism; microarray technology; Microbiology; Microorganisms; multiple targets; Outer membranes; pharmacology; phosphotransferase; Plasmids; reductase; resistance; resistance mechanisms; screening; Sugar; sugars; Transcription activation; transcriptional activation; Triclosan; Triclosan - pharmacology; 생물학; United States > US; South Korea; triclosan; multiple targets; genomic library; resistance
• ISSN: 1225-8873; 1976-3794; 1976-3794
• DOI: 10.1007/s12275-012-2439-0

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.