Artikel ; Online: The ArsQ permease and transport of the antibiotic arsinothricin.
2023 Band 119, Heft 4, Seite(n) 505–514
Abstract: The pentavalent organoarsenical arsinothricin (AST) is a natural product synthesized by the rhizosphere bacterium Burkholderia gladioli GSRB05. AST is a broad-spectrum antibiotic effective against human pathogens such as carbapenem-resistant Enterobacter ...
| Abstract | The pentavalent organoarsenical arsinothricin (AST) is a natural product synthesized by the rhizosphere bacterium Burkholderia gladioli GSRB05. AST is a broad-spectrum antibiotic effective against human pathogens such as carbapenem-resistant Enterobacter cloacae. It is a non-proteogenic amino acid and glutamate mimetic that inhibits bacterial glutamine synthetase. The AST biosynthetic pathway is composed of a three-gene cluster, arsQML. ArsL catalyzes synthesis of reduced trivalent hydroxyarsinothricin (R-AST-OH), which is methylated by ArsM to the reduced trivalent form of AST (R-AST). In the culture medium of B. gladioli, both trivalent species appear as the corresponding pentavalent arsenicals, likely due to oxidation in air. ArsQ is an efflux permease that is proposed to transport AST or related species out of the cells, but the chemical nature of the actual transport substrate is unclear. In this study, B. gladioli arsQ was expressed in Escherichia coli and shown to confer resistance to AST and its derivatives. Cells of E. coli accumulate R-AST, and exponentially growing cells expressing arsQ take up less R-AST. The cells exhibit little transport of their pentavalent forms. Transport was independent of cellular energy and appears to be equilibrative. A homology model of ArsQ suggests that Ser320 is in the substrate binding site. A S320A mutant exhibits reduced R-AST-OH transport, suggesting that it plays a role in ArsQ function. The ArsQ permease is proposed to be an energy-independent uniporter responsible for downhill transport of the trivalent form of AST out of cells, which is oxidized extracellularly to the active form of the antibiotic. |
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| Mesh-Begriff(e) | Humans ; Membrane Transport Proteins/metabolism ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/metabolism ; Escherichia coli/metabolism ; Arsenicals/metabolism ; Escherichia coli Proteins/metabolism ; Symporters/metabolism ; Biological Transport, Active |
| Chemische Substanzen | Membrane Transport Proteins ; arsinothricin ; Anti-Bacterial Agents ; Arsenicals ; Escherichia coli Proteins ; Symporters |
| Sprache | Englisch |
| Erscheinungsdatum | 2023-02-24 |
| Erscheinungsland | England |
| Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 619315-8 |
| ISSN | 1365-2958 ; 0950-382X |
| ISSN (online) | 1365-2958 |
| ISSN | 0950-382X |
| DOI | 10.1111/mmi.15045 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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