Chemical-genetic identification of the biochemical targets of polyalkyl guanidinium biocides
| dc.contributor.author | Bowie, Drew | |
| dc.contributor.author | Parvizi, Paria | |
| dc.contributor.author | Duncan, Dustin | |
| dc.contributor.author | Nelson, Christopher J. | |
| dc.contributor.author | Fyles, Thomas M. | |
| dc.date.accessioned | 2020-10-20T17:44:29Z | |
| dc.date.available | 2020-10-20T17:44:29Z | |
| dc.date.copyright | 2013 | en_US |
| dc.date.issued | 2013 | |
| dc.description.abstract | Alkylated guanidinium compounds exhibit microbiocidal activity in marine environments, yet the mode of action of these compounds has not been defined. A comprehensive chemical-genetic approach in budding yeast was used to define the biological processes affected by these compounds. N-Butyl-N′-decylguanidinium and N-hexyl-N′-(3-hydroxypropyl)-N′′-octylguanidinium chlorides were shown to prevent yeast growth in a dose-dependent manner. All non-essential genes required for tolerance of sub-lethal amounts of these biocides were identified. These unbiased and systematic screens reveal the two related guanidinium compounds have a non-overlapping spectrum of targets in vivo. A functional tryptophan biosynthetic pathway is essential for tolerance of both biocides, which identifies tryptophan amino acid import as one process affected by these compounds. Further analysis of hypersensitive gene lists demonstrates that the substitutions on alkylated guanidiums confer important functional differences in vivo: one derivative renders the ability to generate acidic vacuoles essential, while the other is synthetically lethal with mutants in the transcriptional response to chemical stress. Altogether the results define the common and distinct biological processes affected by biocidal alkylated guanidinium salts. | en_US |
| dc.description.reviewstatus | Reviewed | en_US |
| dc.description.scholarlevel | Faculty | en_US |
| dc.description.sponsorship | The discovery and development of polyalkyl guanidinium biocides was achieved through the efforts of Christina Pinelli, Dean Amantea, Ryan Bonfield, Avril Brett, Sarah Mooi, and especially Bob Rowe over many years. The sustained support of the Natural Sciences and Engineering and Research Council of Canada (NSERC) is gratefully acknowledged. Research in the CJN lab is support by operating grants from NSERC and the Canadian Cancer Society Research Institute (CCSRI). | en_US |
| dc.identifier.citation | Bowie, D., Parvizi, P., Duncan, D., Nelson, C. J., & Fyles, T. M. (2013). Chemicalgenetic identification of the biochemical targets of polyalkyl guanidinium biocides. Organic & Biomolecular Chemistry, 11(26), 4359-4366. https://doi.org/10.1039/c3ob40593a | en_US |
| dc.identifier.uri | https://doi.org/10.1039/c3ob40593a | |
| dc.identifier.uri | http://hdl.handle.net/1828/12242 | |
| dc.language.iso | en | en_US |
| dc.publisher | Organic & Biomolecular Chemistry | en_US |
| dc.subject.department | Department of Biochemistry and Microbiology | |
| dc.subject.department | Department of Chemistry | |
| dc.title | Chemical-genetic identification of the biochemical targets of polyalkyl guanidinium biocides | en_US |
| dc.type | Article | en_US |