Metabolism of Sulfamethoxazole by the Model Plant Arabidopsis thaliana

Abstract

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.

An assessment of Pleurotus ostreatus to remove sulfonamides, and its role as a biofilter based on its own spent mushroom substrate

“…enzymatic oxidation of SMX by laccase for 24 h yielded 4 transformation products, the typical transformation products of SAs were identified and are shown in Figs S2 C, D and E, and the characteristic transformation product of SMX shown in Fig.S2B, which is e in agreement with the results of other researchers(Majewsky et al 2015;Huynh and Reinhold 2019;Reis et al 2020). The proposed degradation pathway is in Fig.3.…”

Influence of Sulfonamide Contamination Derived from Veterinary Antibiotics on Plant Growth and Development

“…Although further uptake studies of sulfonamides from the soil to plants are required to understand the absorption and accumulation of veterinary medicines and their derived metabolites in plants, some of these studies [43,60] have suggested that the phyto-metabolism of antibiotics is a potentially significant route of human exposure to trace concentrations of antibiotics, which has prompted concerns about the development of antibiotic resistance in humans [76].…”

Systematic identification of trimethoprim metabolites in lettuce

“…In phase II, xenobiotics or their activated phase I metabolites undergo conjugation with endogenous plant compounds [14]. Conjugation of xenobiotics in plants may happen with various substituents, such as acetyl, methyl, and sulfate groups, glucuronic acid, cladinose, glucose, glutathione, glucopyranosyloxy and malonyl groups, pterin, methyl salicylate, leucyl, glutamic acid, and glutamine molecules, amongst others [15][16][17][18][19]. As a result, phase II might yield "endless" conjugation possibilities in plants as a detoxification mechanism.…”

“…Indeed, only a few studies on the metabolization of sulfonamides (i.e. sulfamethoxazole, sulfadiazine, and sulfamethazine) [15][16][17]30], clarithromycin [16], and ofloxacin [31] in plants have been reported. For example, clarithromycin follows four major metabolic pathways in lettuce, including cladinose hydrolysis, demethylation, methylation, and oxidation [16].…”

“…For example, clarithromycin follows four major metabolic pathways in lettuce, including cladinose hydrolysis, demethylation, methylation, and oxidation [16]. On the other hand, the main transformation pathways reported for sulphonamides are oxidation, hydroxylation, and desulfation during phase I, and conjugation with glucose, N4-glycosyl-glycoside, pterin, methylsalicylate glutathione, glucuronic acid, and leucine during phase II [15][16][17]30]. These studies show that in spite of some common phase I metabolites, AB metabolization in plants is rather diverse and unpredictable.…”