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A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria
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Kim, Dae-Wi, Thawng, Cung Nawl, Lee, Kihyun, Wellington, E. M. H. and Cha, Chang-Jun (2019) A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria. Environment International, 127 . pp. 206-215. doi:10.1016/j.envint.2019.03.046 ISSN 0160-4120.
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WRAP-novel-sulfonamide-resistance-mechanism-tow-component-actinobacteria-Wellington-2019.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2838Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/j.envint.2019.03.046
Abstract
Sulfonamide-degrading bacteria have been discovered in various environments, suggesting the presence of novel resistance mechanisms via drug inactivation. In this study, Microbacterium sp. CJ77 capable of utilizing various sulfonamides as a sole carbon source was isolated from a composting facility. Genome and proteome analyses revealed that a gene cluster containing a flavin-dependent monooxygenase and a flavin reductase was highly up-regulated in response to sulfonamides. Biochemical analysis showed that the two-component monooxygenase system was key enzymes for the initial cleavage of sulfonamides. Co-expression of the two-component system in Escherichia coli conferred decreased susceptibility to sulfamethoxazole, indicating that the genes encoding drug-inactivating enzymes are potential resistance determinants. Comparative genomic analysis revealed that the gene cluster containing sulfonamide monooxygenase (renamed as sulX) and flavin reductase (sulR) was highly conserved in a genomic island shared among sulfonamide-degrading actinobacteria, all of which also contained sul1-carrying class 1 integrons. These results suggest that the sulfonamide metabolism may have evolved in sulfonamide-resistant bacteria which had already acquired the class 1 integron under sulfonamide selection pressures. Furthermore, the presence of multiple insertion sequence elements and putative composite transposon structures containing the sulX gene cluster indicated potential mobilization. This is the first study to report that sulX responsible for both sulfonamide degradation and resistance is prevalent in sulfonamide-degrading actinobacteria and its genetic signatures indicate horizontal gene transfer of the novel resistance gene.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
| Library of Congress Subject Headings (LCSH): | Actinobacteria, Monooxygenases, Flavins | |||||||||
| Journal or Publication Title: | Environment International | |||||||||
| Publisher: | Pergamon Press | |||||||||
| ISSN: | 0160-4120 | |||||||||
| Official Date: | June 2019 | |||||||||
| Dates: |
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| Volume: | 127 | |||||||||
| Page Range: | pp. 206-215 | |||||||||
| DOI: | 10.1016/j.envint.2019.03.046 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 5 April 2019 | |||||||||
| Date of first compliant Open Access: | 5 April 2019 | |||||||||
| RIOXX Funder/Project Grant: |
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