Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine , Florida International University , Miami , Florida 33199 , United States.
Jiangsu Key Laboratory for Organic Waste Utilization, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization, College of Resources and Environmental Sciences , Nanjing Agricultural University , Nanjing 210095 , China.
Environ Sci Technol. 2019 Jun 4;53(11):6182-6191. doi: 10.1021/acs.est.9b01187. Epub 2019 May 14.
Organoarsenical biotransformations are important components of the global cycling of arsenic. Roxarsone (3-nitro-4-hydroxybenzenearsenate or Rox(V)) and nitarsone (4-nitrobenzene arsenate or Nit(V)) are synthetic aromatic organoarsenicals used in the poultry industry as additives to prevent coccidiosis and improve feed efficiency. Here, we describe a novel pathway of resistance to roxarsone and nitarsone involving biotransformation of their trivalent forms (Rox(III)) and (Nit(III)) to the trivalent organoarsenicals HAPA(III) and pAsA(III), coupled to active extrusion of the aromatic aminobenezylarsenicals from the cells. The arsE, arsF, and arsG were cloned from the arsenic island in the chromosome of Shewanella putrefaciens 200. When expressed in Escherichia coli together, but not alone, arsEFG conferred resistance to Rox(III) and Nit(III) and decreased the accumulation of both. The cells transformed Rox(III) or Nit(III) to HAPA(III) or pAsA(III) by reducing the nitro group to an amine. Everted membrane vesicles from cells expressing arsG accumulated HAPA(III) or pAsA(III). Our data indicate that ArsE and ArsF together reduce Rox(III) or Nit(III) to HAPA(III) or pAsA(III), which are extruded from the cells by the efflux permease ArsG. Identification of the coupled pathway of ArsE, ArsF, and ArsG catalysis is a molecular description of a novel pathway for resistance to roxarsone and nitarsone.
有机胂的生物转化是砷全球循环的重要组成部分。罗氧头孢（3-硝基-4-羟基苯胂酸或 Rox(V)）和硝氧头孢（4-硝基苯胂酸或 Nit(V)）是用于家禽业的合成芳香族有机胂化合物，用作添加剂以预防球虫病和提高饲料效率。在这里，我们描述了一种新的罗氧头孢和硝氧头孢耐药途径，涉及将它们的三价形式（Rox(III)）和（Nit(III)）生物转化为三价有机胂 HAPA(III)和 pAsA(III)，并与芳香族氨基苯胂从细胞中主动外排偶联。arsE、arsF 和 arsG 从 Shewanella putrefaciens 200 染色体中的砷岛克隆。当在大肠杆菌中一起表达而不是单独表达时，arsEFG 赋予对 Rox(III)和 Nit(III)的抗性，并减少了两者的积累。细胞通过将硝基还原为胺将 Rox(III)或 Nit(III)转化为 HAPA(III)或 pAsA(III)。表达 arsG 的细胞的外翻膜泡积累了 HAPA(III)或 pAsA(III)。我们的数据表明， ArsE 和 ArsF 一起将 Rox(III)或 Nit(III)还原为 HAPA(III)或 pAsA(III)，这些物质通过外排转运蛋白 ArsG 从细胞中排出。鉴定 ArsE、ArsF 和 ArsG 催化的偶联途径是对罗氧头孢和硝氧头孢耐药的新途径的分子描述。
