Metabolism of Sulfamethoxazole by the Model Plant Arabidopsis thaliana

Phytometabolism of antibiotics is a potentially significant route of human exposure to trace concentrations of antibiotics, prompting concerns about antibiotic resistance. The present study evaluated the metabolism of sulfamethoxazole (SMX), a commonly used sulfonamide antibiotic, by Arabidopsis thaliana. SMX was intensively metabolized by A. thaliana, with only 1.1% of SMX in plant tissues present as the parent compound after 10 days of exposure. Untargeted screening of extractable metabolites revealed that N-glycosylation was the main transformation pathway of SMX in A. thaliana plants, with N⁴-glycosyl-SMX accounting for more than 80% of the extractable metabolites. Additionally, N⁴-glycosyl-glycoside SMX accounted for up to 4.4% of the extractable metabolites, indicating glycosylation of N⁴-glycosyl-SMX. The majority of minor extractable SMX metabolites were also conjugates of the parent compound, such as pterin-SMX and methyl salicylate-SMX conjugates. In ¹⁴C-SMX trials, ¹⁴C-radioactivity was detected in both extractable and bound residues in plant tissues. Extractable residues, which included ¹⁴C-SMX and its soluble metabolites, accounted for 35.8-43.6% of the uptaken ¹⁴C-radioactivity, while bound residues were 56.4-64.2%. Approximately 27.0% of the initially applied ¹⁴C-radioactivity remained in the culture media at the conclusion of the experiments, composed of both ¹⁴C-SMX and its metabolites, likely due to plant excretion.