A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria
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....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Environment International |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412019302223 |
| _version_ | 1811205293679312896 |
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| author | Dae-Wi Kim Cung Nawl Thawng Kihyun Lee Elizabeth M.H. Wellington Chang-Jun Cha |
| author_facet | Dae-Wi Kim Cung Nawl Thawng Kihyun Lee Elizabeth M.H. Wellington Chang-Jun Cha |
| author_sort | Dae-Wi Kim |
| collection | DOAJ |
| description | 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. Keywords: Sulfonamide resistance, Sulfonamide degradation, Genomic island, Composite transposon, Horizontal gene transfer |
| first_indexed | 2024-04-12T03:28:37Z |
| format | Article |
| id | doaj.art-8c73d290ee5440b0a02527431fab9fc0 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-12T03:28:37Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-8c73d290ee5440b0a02527431fab9fc02022-12-22T03:49:36ZengElsevierEnvironment International0160-41202019-06-01127206215A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteriaDae-Wi Kim0Cung Nawl Thawng1Kihyun Lee2Elizabeth M.H. Wellington3Chang-Jun Cha4Department of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong 17456, Republic of KoreaDepartment of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong 17456, Republic of KoreaDepartment of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong 17456, Republic of KoreaSchool of Life Sciences, University of Warwick, Coventry CV4 7AL, United KingdomDepartment of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong 17456, Republic of Korea; Corresponding author.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. Keywords: Sulfonamide resistance, Sulfonamide degradation, Genomic island, Composite transposon, Horizontal gene transferhttp://www.sciencedirect.com/science/article/pii/S0160412019302223 |
| spellingShingle | Dae-Wi Kim Cung Nawl Thawng Kihyun Lee Elizabeth M.H. Wellington Chang-Jun Cha A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria Environment International |
| title | A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria |
| title_full | A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria |
| title_fullStr | A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria |
| title_full_unstemmed | A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria |
| title_short | A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria |
| title_sort | novel sulfonamide resistance mechanism by two component flavin dependent monooxygenase system in sulfonamide degrading actinobacteria |
| url | http://www.sciencedirect.com/science/article/pii/S0160412019302223 |
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