Metabolic Responses to Arsenite Exposure Regulated through Histidine Kinases PhoR and AioS in Agrobacterium tumefaciens 5A

Arsenite (As-III) oxidation is a microbially-catalyzed transformation that directly impacts arsenic toxicity, bioaccumulation, and bioavailability in environmental systems. The genes for As-III oxidation (aio) encode a periplasmic As-III sensor AioX, transmembrane histidine kinase AioS, and cognate regulatory partner AioR, which control expression of the As-III oxidase AioBA. The aio genes are under ultimate control of the phosphate stress response via histidine kinase PhoR. To better understand the cell-wide impacts exerted by these key histidine kinases, we employed H-1 nuclear magnetic resonance (H-1 NMR) and liquid chromatography-coupled mass spectrometry (LC-MS) metabolomics to characterize the metabolic profiles of Delta phoR and Delta aioS mutants of Agrobacterium tumefaciens 5A during As-III oxidation. The data reveals a smaller group of metabolites impacted by the Delta aioS mutation, including hypoxanthine and various maltose derivatives, while a larger impact is observed for the Delta phoR mutation, influencing betaine, glutamate, and different sugars. The metabolomics data were integrated with previously published transcriptomics analyses to detail pathways perturbed during As-III oxidation and those modulated by PhoR and/or AioS. The results highlight considerable disruptions in central carbon metabolism in the Delta phoR mutant. These data provide a detailed map of the metabolic impacts of As-III, PhoR, and/or AioS, and inform current paradigms concerning arsenic-microbe interactions and nutrient cycling in contaminated environments.