Discovery and Characterization of Polymyxin-Resistance Genes pmrE and pmrF from Sediment and Seawater Microbiome
ABSTRACT Polymyxins are the last-line antibiotics used to treat Gram-negative pathogens. Thus, the discovery and biochemical characterization of the resistance genes against polymyxins are urgently needed for diagnosis, treatment, and novel antibiotic design. Herein, we report novel polymyxin-resist...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-02-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02736-22 |
| _version_ | 1811164409809076224 |
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| author | Hwanjin Joo Hyunuk Eom Youna Cho Mina Rho Woon Ju Song |
| author_facet | Hwanjin Joo Hyunuk Eom Youna Cho Mina Rho Woon Ju Song |
| author_sort | Hwanjin Joo |
| collection | DOAJ |
| description | ABSTRACT Polymyxins are the last-line antibiotics used to treat Gram-negative pathogens. Thus, the discovery and biochemical characterization of the resistance genes against polymyxins are urgently needed for diagnosis, treatment, and novel antibiotic design. Herein, we report novel polymyxin-resistance genes identified from sediment and seawater microbiome. Despite their low sequence identity against the known pmrE and pmrF, they show in vitro activities in UDP-glucose oxidation and l-Ara4N transfer to undecaprenyl phosphate, respectively, which occur as the part of lipid A modification that leads to polymyxin resistance. The expression of pmrE and pmrF also showed substantially high MICs in the presence of vanadate ions, indicating that they constitute polymyxin resistomes. IMPORTANCE Polymyxins are one of the last-resort antibiotics. Polymyxin resistance is a severe threat to combat multidrug-resistant pathogens. Thus, up-to-date identification and understanding of the related genes are crucial. Herein, we performed structure-guided sequence and activity analysis of five putative polymyxin-resistant metagenomes. Despite relatively low sequence identity to the previously reported polymyxin-resistance genes, at least four out of five discovered genes show reactivity essential for lipid A modification and polymyxin resistance, constituting antibiotic resistomes. |
| first_indexed | 2024-04-10T15:22:09Z |
| format | Article |
| id | doaj.art-f974ffb453634a47bb2302f52f94d9f2 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-10T15:22:09Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-f974ffb453634a47bb2302f52f94d9f22023-02-14T14:15:49ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-02-0111110.1128/spectrum.02736-22Discovery and Characterization of Polymyxin-Resistance Genes pmrE and pmrF from Sediment and Seawater MicrobiomeHwanjin Joo0Hyunuk Eom1Youna Cho2Mina Rho3Woon Ju Song4Department of Chemistry, Seoul National University, Seoul, Republic of KoreaDepartment of Chemistry, Seoul National University, Seoul, Republic of KoreaDepartment of Computer Science, Hanyang University, Seoul, Republic of KoreaDepartment of Computer Science, Hanyang University, Seoul, Republic of KoreaDepartment of Chemistry, Seoul National University, Seoul, Republic of KoreaABSTRACT Polymyxins are the last-line antibiotics used to treat Gram-negative pathogens. Thus, the discovery and biochemical characterization of the resistance genes against polymyxins are urgently needed for diagnosis, treatment, and novel antibiotic design. Herein, we report novel polymyxin-resistance genes identified from sediment and seawater microbiome. Despite their low sequence identity against the known pmrE and pmrF, they show in vitro activities in UDP-glucose oxidation and l-Ara4N transfer to undecaprenyl phosphate, respectively, which occur as the part of lipid A modification that leads to polymyxin resistance. The expression of pmrE and pmrF also showed substantially high MICs in the presence of vanadate ions, indicating that they constitute polymyxin resistomes. IMPORTANCE Polymyxins are one of the last-resort antibiotics. Polymyxin resistance is a severe threat to combat multidrug-resistant pathogens. Thus, up-to-date identification and understanding of the related genes are crucial. Herein, we performed structure-guided sequence and activity analysis of five putative polymyxin-resistant metagenomes. Despite relatively low sequence identity to the previously reported polymyxin-resistance genes, at least four out of five discovered genes show reactivity essential for lipid A modification and polymyxin resistance, constituting antibiotic resistomes.https://journals.asm.org/doi/10.1128/spectrum.02736-22polymyxinantibiotic resistancemetagenomeUDP-glucose dehydrogenaseundecaprenyl-phosphate 4-deoxy-4-formamido-l-arabinose transferase |
| spellingShingle | Hwanjin Joo Hyunuk Eom Youna Cho Mina Rho Woon Ju Song Discovery and Characterization of Polymyxin-Resistance Genes pmrE and pmrF from Sediment and Seawater Microbiome Microbiology Spectrum polymyxin antibiotic resistance metagenome UDP-glucose dehydrogenase undecaprenyl-phosphate 4-deoxy-4-formamido-l-arabinose transferase |
| title | Discovery and Characterization of Polymyxin-Resistance Genes pmrE and pmrF from Sediment and Seawater Microbiome |
| title_full | Discovery and Characterization of Polymyxin-Resistance Genes pmrE and pmrF from Sediment and Seawater Microbiome |
| title_fullStr | Discovery and Characterization of Polymyxin-Resistance Genes pmrE and pmrF from Sediment and Seawater Microbiome |
| title_full_unstemmed | Discovery and Characterization of Polymyxin-Resistance Genes pmrE and pmrF from Sediment and Seawater Microbiome |
| title_short | Discovery and Characterization of Polymyxin-Resistance Genes pmrE and pmrF from Sediment and Seawater Microbiome |
| title_sort | discovery and characterization of polymyxin resistance genes pmre and pmrf from sediment and seawater microbiome |
| topic | polymyxin antibiotic resistance metagenome UDP-glucose dehydrogenase undecaprenyl-phosphate 4-deoxy-4-formamido-l-arabinose transferase |
| url | https://journals.asm.org/doi/10.1128/spectrum.02736-22 |
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