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Mechanism of Drug Resistance in Staphylococcus aureus and Future Drug Discovery
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Felipe Wakasuqui, Ana Leticia Gori Lusa, Sven Falke, Christian Betzel, Carsten Wrenger
Trimethoprim is a pyrimidine analogue that acts as an inhibitor of the dihydrofolate reductase. Sulfamethoxazole is a sulfonamide and competitive inhibitor of the dihydropteroate synthetase. Both drugs target the same metabolic pathway, disrupting folate biosynthesis, affecting the synthesis of nucleotides. They are commonly applied together, which diminishes occurrence of resistance (Wormser et al., 1982). Resistance to sulfamethoxazole is caused by mutations in the DHPS gene (Hampele et al., 1997). Two genetics mechanisms are known to confer resistance to trimethoprim, mutation in the dihydrofolate reductase gene (dfrB), and genes that encode variants of dihydrofolate reductase (i.e. dfrA, dfrG, and dfrK) (Nurjadi et al., 2014), considering the dfrG gene to be the most prevalent cause of resistance (Nurjadi et al., 2015).
Influence of ionizing radiation on the antimicrobial activity of the antibiotics sulfamethoxazole and trimethoprim
Published in Journal of Environmental Science and Health, Part A, 2018
G. Sági, K. Szabacsi, L. Szabó, R. Homlok, K. Kovács, C. Mohácsi-Farkas, S. D. Pillai, E. Takács, L. Wojnárovits
Municipal and industrial wastewaters especially from pharmaceutical industries contain antibiotic residues, which can potentially result in the proliferation of antimicrobial resistant bacterial strains in the receiving waters.[1–4] Ionizing radiation technology is effective in degrading antibiotic compounds from such waste streams [5–8] and can, therefore, have the potential for remediating pharmaceutical wastewater.[9–11] Sulfamethoxazole (SMX), a sulfonamide antibiotic in combination with trimethoprim (TMP) is widely used in human and animal healthcare.[12,13] Unfortunately, these compounds are present in wastewater effluent, sewage sludges and in freshwater sources.[14–16] The effect of ionizing radiation on the removal efficiency, degradation mechanisms and ecotoxicity of SMX or TMP solutions have been previously described.[17–20] However, there have been no reports, to the best of our knowledge, on the efficacy of this technology in terms of residual antimicrobial activity either singly or when present in mixtures of these two antimicrobials.
Determination of antibiotics during treatment of hospital wastewater using automated solid-phase extraction followed by UHPLC-MS: occurrence, removal and environmental risks
Published in Environmental Technology, 2023
Zamazwi Lukhanyiso Mthiyane, Nkosinathi Makhubela, Hlengilizwe Nyoni, Lawrence Mzukisi Madikizela, Bethusile Rejoice Maseko, Somandla Ncube
The concentration of the antibiotics in effluents from the hospital WWTP ranged from not detected (metronidazole and norfloxacin) to 0.383 ng/mL for sulfamethoxazole (Table 2). Sulfamethoxazole is a common antibiotic detected in African wastewater effluents [8,9,11], and its high concentration value in the current study was not a surprise. The other commonly detected antibiotic, trimethoprim was also detected at 0.0130 ng/mL. Most of the antibiotics in the current study were within the 0.1 ng/mL limit value recommended by Le Page et al. [6] except for gentamicin and sulfamethoxazole which recorded 0.1189 and 0.3829 ng/mL, respectively. The concentration of sulfamethoxazole is comparable to those previously reported in South Africa [44,41].
DFT studies of temperature effect on coordination chemistry of Cu(II)-trimethoprim complexes
Published in Journal of Coordination Chemistry, 2018
Malik Zaheer Ahmed, Uzma Habib
Trimethoprim {(2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine, TMP} belongs to a synthetic antibacterial agent and diaminopyrimidine (pyridine-3,4-diamine) compound group. Dihydrofolate reductase (DHFR) is the target enzyme of trimethoprim. This enzyme catalyzes the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate in the presence of NADPH. Trimethoprim is a good inhibitor of bacterial dihydrofolate reductase and is used to prevent the conversion of dihydrofolic acid to tetrahydrofolic acid [1, 2] (Figure 1).