Sulfonamide Antibiotics Research Articles

Binding order of substrate and cofactor in sulfonamide monooxygenase during sulfa drug degradation: in silico studies

For decades, sulfonamide antibiotics have been used across industries such as agriculture and animal husbandry. However, the use and inadvertent misuse of these antibiotics have resulted in the advent of sulfonamide-drug-resistant strains due to antibiotic pollution. Enzymatic bioremediation of antibiotics remains a potential emerging solution to combat antibiotic pollution. Here, we propose an enzymatic model for the degradation of sulfonamides by Microbacterium sp. We have employed a multi-pronged computational strategy involving – protein structure modelling, ligand docking and molecular dynamics simulations to decipher a plausible binding order for the enzymatic degradation of sulfonamides by the bacterial sulfonamide monooxygenase, SulX. Our results enable us to predict that this degradation is achieved through the sequential binding of the antibiotic sulfonamide followed by the reduced flavin cofactor FMNH2, thereby laying the computational foundation for further advancements in enzyme-mediated degradation of the antibiotic. We also provide a list of experiments which may be performed to verify and follow-up on our in-silico studies. Communicated by Ramaswamy H. Sarma

Removal of sulfonamide antibiotics by non-free radical dominated peroxymonosulfate oxidation catalyzed by cobalt-doped sulfur-containing biochar from sludge

The reuse of activated sludge as a solid waste is severely underutilized due to the limitations of traditional treatment and disposal methods. Given that, the sulfur-containing activated sludge catalyst doped with cobalt (SK-Co(1.0)) was successfully prepared by one-step pyrolysis and calcinated at 850 ℃. The generation of CoSx was successfully characterized by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), indicating that the sulfur inside the sludge was the anchoring site for the externally doped cobalt. Cobalt (Ⅱ) (Co2+), as the main adsorption site for peroxymonosulfate(PMS), formed a complex (SK-Co(1.0)-PMS* ) and created the conditions for the generation of surface radicals. The SK-Co(1.0)/PMS system showed high degradation efficiency and apparent rate constants for Sulfamethoxazole (SMX) (91.56% and 0.187 min−1) and Sulfadiazine (SDZ) (90.73% and 0.047 min−1) within 10 min and 30 min, respectively. Three sites of generation of 1O2, which played a dominant role in the degradation of SMX and SDZ in the SK-Co(1.0)/PMS system, were summarized as：sulfur vacancies (SVs), the Co3+/Co2+ cycles promoted by sulfur(S) species, oxygen-containing functional groups (C-O). The degradation mechanisms and pathways had been thoroughly investigated using DFT calculations. In view of this, a new idea for the resource utilization of activated sludge solid waste was provided and a new strategy for wastewater remediation was proposed.

Transport of sulfanilamide in saturated porous media under different solution chemistry conditions: role of physicochemical characteristics of soils.

Identification of the transport of sulfonamide antibiotics in soils facilitates a better understanding of the environmental fate and behaviors of these ubiquitous contaminants. In this study, the mobility properties of sulfanilamide (SNM, a typical sulfonamide antibiotic) through saturated soils with different physicochemical characteristics were investigated. The results showed that the physicochemical characteristics controlled SNM mobility. Generally, the mobility of SNM was positively correlated with CEC values and soil organic matter content, which was mainly related to the interactions between the organic matter in soils and SNM molecules via π-π stacking, H-bonding, ligand exchange, and hydrophobic interaction. Furthermore, higher clay mineral content and lower sand content were beneficial for restraining SNM transport in the soils. Unlike Na+, Cu2+ ions could act as bridging agents between the soil grains and SNM molecules, contributing to the relatively weak transport of SNM. Furthermore, the trend of SNM mobility in different soil columns was unaffected by solution pH (5.0-9.0). Meanwhile, for a given soil, the SNM mobility was promoted as the solution pH values increased, which was caused by the enhanced electrostatic repulsion between SNM- species and soil particles as well as the declined hydrophobic interaction between SNM and soil organic matter. The obtained results provide helpful information for the contribution of soil physicochemical characteristics to the transport behaviors of sulfonamide antibiotics in soil-water systems.

Low uptake of pharmaceuticals in edible mushrooms grown in polluted biogas digestate

The uptake dynamics of two sulfonamide antibiotics, two fluoroquinolone antibiotics, and the anticonvulsant carbamazepine during the cultivation of two species of edible mushrooms (Agaricus subrufescens and A. bisporus) was investigated. None of the antibiotics were accumulated by the mushrooms, while carbamazepine and its transformation product carbamazepine-10,11-epoxide were taken up by A. bisporus fruiting body but only in small amounts (up to 0.76 and 1.85 μg kg−1 dry weight, respectively). The sulfonamides were quickly removed from the mushroom growth substrate, while the recalcitrant fluoroquinolones and carbamazepine were only partially removed. Dissipation half-lives were generally lower for A. subrufescens than A. bisporus, but A. subrufescens was also grown at a slightly higher culture temperature. A. subrufescens also showed a lower uptake of contaminants. Comparison of maximum dietary intake with other common exposure sources showed that these mushrooms can safely be eaten although produced on a polluted substrate, with respect to the investigated compounds.

Revealing the response characteristics of periphyton biomass and community structure to sulfamethoxazole exposure in aquaculture water: The perspective of microbial network relationships

The widespread application of sulfonamide antibiotics in aquaculture has raised concerns about their adverse environmental impacts. Periphyton plays a crucial role in the aquatic ecosystem. In this study, we examined sulfamethoxazole (SMX) effects on the community structure and interactions of periphyton in simulated aquaculture water. Our findings indicated that the total biomass of periphyton decreased, while the biomass of periphytic algae and the secretion of extracellular polymeric substances (EPS) increased at 0.7 × 10−3 mg/L. Under higher SMX concentrations (5 mg/L and 10 mg/L), periphyton growth was severely inhibited, the microbial community structure of periphyton were sharply altered, characterized by the cyanobacteria growth suppression and decrease in the diversity index of community. Furthermore, elevated SMX concentrations (5 mg/L and 10 mg/L) increased the ratio of negative relationships from 45.4% to 49.4%, which suggested that high SMX concentrations promoted potential competition among microbes and disrupted the microbial food webs in periphyton. The absolute abundance of sul1 and sul2 genes in T2 and T3 groups were 2–3 orders of magnitude higher than those in control group after 30 days of SMX exposure, which elevated the risk of resistance gene enrichment and dissemination in the natural environment. The study contributes to our understanding of the detrimental effects of antibiotic pollution, which can induce changes in the structure and interaction relationship of microbial communities in aquaculture water.

A Comprehensive Review of Sulfonamide Hypersensitivity: Implications for Clinical Practice.

Sulfonamides, which are drugs commonly prescribed in hospital and outpatient settings, have historically been associated with a high incidence of hypersensitivity reactions. It is believed that there is an increased risk of cross-reactions with other drugs that contain this functional group in their structure. However, it has not been conclusively established that the sulfonamide group is the sole cause of hypersensitivity reactions, as non-antibiotic sulfonamides do not share the same accessory groups with antibiotic sulfonamides. Therefore, cross-reactivity between different types of sulfonamides and sulfonamide-type antibiotics is not clearly demonstrated, and allergic reactions may involve other mechanisms. Misinformation about this topic can lead to inappropriate use of alternative antibiotics with lower efficacy or higher adverse effects, contributing to antibiotic resistance. It is crucial to individualize and monitor patients with a history of allergies to sulfonamide-type antibiotics when introducing a new drug containing sulfa and manage any adverse reactions promptly. Desensitization protocols may be a viable option for patients who specifically benefit from these antibiotics, particularly those who are immunosuppressed. This article provides a descriptive bibliographic review to update information on sulfa allergy, its prevalence, management, and recommendations to prevent such reactions and optimize pharmacotherapy, without underusing these drugs.

The determination of 11 sulfonamide antibiotics in water and foods by developing a N-rich magnetic covalent organic framework combined with ultra-high performance liquid chromatography-tandem mass spectrometry.

The concentration of antibiotic residues in water and animal-derived foods is low and the matrix is complex, and effective extraction of antibiotic residues in them is a key factor for accurate quantification. It is important to establish a rapid and effective method for the analytical determination of antibiotics in water and foods. In this study, a type of novel magnetic COF (Fe3O4@SiO2@PDE-TAPB-COF) was synthesized and characterized. Moreover, Fe3O4@SiO2@PDE-TAPB-COF combined with ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine the 11 sulfonamide antibiotics (SAs) in water and food. The parameters including pH, adsorption amount, adsorption time, type of elution solvent and elution time were optimized. Under the optimal conditions, the standard curves of 11 SAs showed good linearity (R 2 > 0.999) in their respective concentration ranges and had lower detection and quantification limits. The spiked recoveries of the developed MSPE-UPLC-MS/MS method for the 11 SAs in water and foods were 74.3-107.2% and 75.1-102.5%, respectively. And the relative standard deviations (RSDs) were less than 9.56% (n = 7). The results indicated that the method can be used for the determination of SAs in foods and water with low detection limits and high sensitivity.

An enhanced Bi/nZVI activated molecular oxygen process for the degradation of sulfonamide antibiotics in a citrate buffering system.

Citric acid (CA) and sodium citrate (NaCA) have been effectively employed to synergize with bismuth-doped nanoscale zero-valent iron (Bi/nZVI) to degrade sulfonamide antibiotics (SAs) without the need for additional H2O2. In the integrated Bi/nZVI-CA/NaCA system, excellent oxidation activity of sulfamethazine (SM2), sulfadiazine (SD) and sulfamethoxazole (SMX) in the mixed solution was obtained. The bimetallic enhancement alongside ligand complexation significantly promoted Bi/nZVI to catalyze molecular oxygen and was conducive to the spontaneous generation of H2O2. Fe(II)[Cit]- was formed in the CA/NaCA system, and then underwent a Fenton-like reaction with spontaneously produced H2O2 to achieve the oxidation of SAs. Long service life was confirmed by the results of characterization, electrochemical analysis, utilization rate (UR), electronic efficiency (EE) and cycling degradation experiments. In the Bi/nZVI-CA/NaCA system, two comparable degradation pathways (hydroxylation and SO2 extrusion) for SM2, SMX and SD were obtained, while another degradation pathway for SMX was reflected in the opening of the N-O bond on the benzene ring. Additionally, post-reactive solution toxicity was assessed to ensure environmental safety. Overall, our findings provide a theoretical research basis for the effective elimination of SAs from contaminated environments.

Urchin-like covalent organic frameworks templated Au@Ag composites for SERS detection of emerging contaminants.

Au@Ag core-shell composites were successfully fabricated on urchin-like covalent organic frameworks (COFs), providing a platform with numerous hot spots for the detection of two categories of emerging contaminants: sulfonamide antibiotics and nanoplastics, using surface-enhanced Raman spectroscopy (SERS). Au seeds (∼10 nm) were generated on the COFs, leveraging the reducing properties of the vinyl and imino groups within the framework. This ensured the growth of dense and uniformly distributed Ag nanoparticles. The COFs exceptionally large surface area (2324 m2 g-1) and high adsorption capacity, significantly contributed to the enrichment and detection of trace pollutants. As a result, using a portable Raman spectrometer, limits of detection of 0.008 μmol L-1 for sulfamethoxazole and 0.029 mg L-1 for polystyrene nanoplastics were achieved.

PH-dependent adsorption of the sulfamethoxazole antibiotic on HKUST-1@CNS nanocomposite corroborating efficiency, mechanistic, and kinetic studies

Sulfonamide antibiotics, such as sulfamethoxazole (SMX), are found to be pollutants mostly generated from pharmaceutical wastewater with very high detection levels.

Metal ion-supported mesoporous silica materials for the removal of sulfamethizole from water

Sulfamethizole (SIZ) exhibited spontaneous, exothermic and fast adsorption on Ni-AAPTMS-SBA-15 within 2 min and maximum adsorption capacity of 188.68 mg g−1, attributing to combined mechanism of electrostatic interaction, complexation and pore-filling.

Mobility of biochar-derived dissolved organic matter and its effects on sulfamerazine transport through saturated soil porous media.

Dissolved organic matter (DOM) released from biochar may impact antibiotic mobility and environmental fate in subsurface environments. Here, DOM samples derived from biochars (BDOM) generated by pyrolyzing corn straw at 300, 450, and 600 °C were employed to elucidate the mobility characteristics of these organic substances and their influences on the transport of sulfamerazine (SMZ, a typical sulfonamide antibiotic) in soil porous media. The results demonstrated that BDOM produced at a lower pyrolysis temperature exhibited greater mobility owing to the weaker hydrophobic and H-bonding interactions between BDOM and soil particles. Additionally and importantly, BDOM facilitated the promotion of SMZ mobility owing to the increased electrostatic repulsion between SMZ- forms and soil grains, the steric hindrance effect induced by the deposition of organic matter, and the competitive retention between SMZ molecules and BDOM. Meanwhile, the promotion effects of BDOM enhanced with improving pyrolysis temperature owing to the promoted deposition of organic matter on soil surfaces and the strengthened electrostatic repulsion. Moreover, the facilitated effects of BDOM on SMZ mobility declined as the solution pH values were raised from 5.0 to 9.0 or the flow rate increased from 0.18 to 0.51 cm min-1. This trend was due to decreased deposition competition and the steric effect caused by decreased retention of BDOM on soil particles. Furthermore, the cation-bridging effect emerged as an important mechanism contributing to the promotion effects of BDOM when the solution contained divalent cations (Cu2+ or Ca2+). Moreover, a two-site non-equilibrium model was used to interpret the controlling mechanisms for the effects of BDOM on the transport of SMZ. Findings from this work highlight that biochar-derived dissolved organic matter can remarkably affect the environmental behaviors of antibiotics in aquatic environments.

Comparison of the effectiveness of UV, UV/VUV photolysis, ozonation, and ozone/UV processes for the removal of sulfonamide antibiotics

UV (254 nm) and UV/VUV (254/185 nm) photolysis, ozonation, and O3/UV combination were investigated and compared for the transformation of two sulfonamide (SAs) antibiotics, sulfamethazine (SMT) and sulfamethoxypyridazine (SMP). Change in toxicity, the effect of bacteria growth inhibition of the treated solutions, and the cost-efficiency of the methods were studied. In UV/VUV radiated solutions, the formation of •OH results in the doubled transformation rate. The relative contribution of various ROS (•OH, 1O2, O2•−) to the transformations were also investigated in the case of UV and UV/VUV photolysis. Both SAs can be eliminated ten times faster during ozonation than UV photolysis; but conversion via ozonation is associated with the formation of products with low reactivity to ozone and has biological effects. The O3/UV process did not enhance the transformation rate but positively affected mineralization and significantly decreased the ecotoxicity of the treated solutions. Ozonation was cost-effective, but O3/UV is a much safer technology to minimize environmental impacts because it effectively reduces the ecotoxicity and the bacterial growth inhibition effect of the treated solution. The observed differences between SMT and SMP are primarily related to the transformation of the N-containing rings. Our results showed a correlation between the reactivity of the N-containing groups of SAs, the rate of mineralization, and the change in ecotoxicity and antibacterial effect and emphasized the need for toxicological characterization of the treated samples. The removal of parent compounds is not sufficient to avoid the release of toxic substances into the environment.

Wastewater surveillance for antibiotics and resistance genes in a river catchment: Spatiotemporal variations and the main drivers

Wastewater-based epidemiology (WBE) is used for mining information about public health such as antibiotics resistance. This study investigated the distribution profiles of six types of antibiotic resistance genes (ARGs) in wastewater and rivers in Wuhu City, China. The levels of ARGs found in the Qingyijiang River were significantly higher than other rivers, and were comparable to effluent levels. Among the ARGs, sulfonamides ARGs and intI1 were the predominant in both wastewaters and rivers. Additionally, the concentrations of ARGs were higher on weekends as opposed to weekdays. Their distribution patterns remained consistent inter-week and inter-season using linear regression analysis (p < 0.001). Interestingly, the occurrence levels of ARGs in wastewaters during spring were significantly higher than in autumn, although insignificant in rivers. The apparent removal rate of ARGs in domestic wastewater sources ranged from 61.52–99.29%, except for qepA (-1.91% to 81.09%), whereas the removal rates in mixed domestic and industrial wastewaters showed a marked decrease (-92.94% to 76.67%). A correlation network analysis revealed that azithromycin and erythromycin were key antibiotics, while blaNDM-1, tetM, tetB, and ermB were identified as key ARGs. Sulfonamide and fluoroquinolone antibiotics, and tetracycline and macrolide ARGs were the primary contributors. Linear mixed models demonstrated that socio-economic variables positively impacted the occurrence levels of ARGs, whereas wastewater flow and river runoff were the negative drivers for their concentrations in wastewaters and surface waters, respectively. Overall, this WBE study contributes to the understanding of spatiotemporal profiles and main drivers of the occurrence of ARGs in wastewater and receiving water.

UV-LED cocatalytic Fe3+/peroxymonosulfate process for the degradation of sulfamethoxypyridazine: Performance, mechanism and DBP formation during postchlorination

Herein, a UV-LED-catalytic Fe3+/peroxymonosulfate homogeneous advanced oxidation process (UV-LED/Fe3+/PMS) was adopted for the removal of sulfamethoxypyridazine (SMP), a commonly used sulfonamide antibiotic (SA), in water. Quenching experiments showed that SO4●–, •OH and Fe(IV) were generated in this system and contributed to the rapid removal of SMP. Generally, acidic media favored SMP degradation, and the contribution rate of active species to SMP removal was highly pH dependent. Higher light intensity and an equal Fe3+/PMS ratio (1:1) were appropriate for SMP removal. The introduction of HCO3−, NO3− and humic acid suppressed the degradation of SMP to different extents, but obvious acceleration was observed in the presence of halide ions. The transformation products were investigated, and their toxicity was also assessed. UV-LED/Fe3+/PMS was capable of controlling trichloromethane (TCM) during postchlorination while increasing the formation of dichloroacetonitrile (DCAN) and trichloronitromethane (TCNM) owing to the generation of precursors having certain functional groups. Prolonging pretreatment time had a positive effect on reducing DBP formation. The presence of humic acid increased the formation of both TCM and DCAN. Furthermore, total trihalomethanes and dihaloacetonitriles increased with increasing bromide concentration, which needs to be considered when adopting the UV-LED/Fe3+/PMS as pretreatment for the abatement of SMP.

Plastic wastes-derived N-doped carbon nanotubes for efficient removal of sulfamethoxazole in high salinity wastewater via nonradical peroxymonosulfate activation

Peroxymonosulfate (PMS) catalytic activation is effective to eliminate organic pollutants from water, thus the development of low-cost and efficient catalysts is significant in applications. The resource conversion of plastic wastes (PWs) into carbon nanotubes (CNTs) is a promising candidate for PMS-based advanced oxidation processes (AOPs), and also a sustainable strategy to realize plastic management and reutilization. Herein, cost-effective PWs-derived N-doped CNTs (N-pCNTs) were synthesized, which displayed efficient activity for PMS activation through an electron transfer pathway (ETP) for sulfamethoxazole (SMX) degradation in high salinity water. The pyrrolic N induced the positively charged surface of N-pCNTs, favoring the electrostatic adsorption of PMS and subsequent generation of active PMS* . A galvanic oxidation process was developed to prove the electron-shuttle dominated ETP for SMX oxidation. Combined with theoretical calculations, the efficiency of ETP was determined by the potential difference between HOMO of SMX and LUMO of N-pCNTs. Such oxidation produced low-toxicity intermediates and resulted in selective degradation of specific sulfonamide antibiotics. This work reveals the feasibility of low-cost N-pCNTs catalysts from PWs serving as an appealing candidate for PMS-AOPs in water remediation, providing a new solution to alleviate environmental issues caused by PWs and also advances the understanding of ETP during PMS activation.

Converting peracetic acid activation by Fe3O4 from nonradical to radical pathway via the incorporation of L-cysteine

Recently, peracetic acid (PAA) based Fenton (-like) processes have received much attention in water treatment. However, these processes are limited by the sluggish Fe(III)/Fe(II) redox circulation efficiency. In this study, L-cysteine (L-Cys), an environmentally friendly electron donor, was applied to enhance the Fe3O4/PAA process for the sulfamethoxazole (SMX) abatement. Surprisingly, the L-Cys incorporation was found not only to enhance the SMX degradation rate constant by 3.2 times but also to switch the Fe(IV) dominated nonradical pathway into the •OH dominated radical pathway. Experiment and theoretical calculation result elucidated -NH2, -SH, and -COOH of L-Cys can increase Fe solubilization by binding to the Fe sites of Fe3O4, while -SH of L-Cys can promote the reduction of bounded/dissolved Fe(III). Similar SMX conversion pathways driven by the Fe3O4/PAA process with or without L-Cys were revealed. Excessive L-Cys or PAA, high pH and the coexisting HCO3−/H2PO4− exhibit inhibitory effects on SMX degradation, while Cl− and humic acid barely affect the SMX removal. This work advances the knowledge of the enhanced mechanism insights of L-Cys toward heterogeneous Fenton (-like) processes and provides experimental data for the efficient treatment of sulfonamide antibiotics in the water treatment.

An efficient, recyclable and stable immobilized enzyme cascade catalytic system with visible-light driven for the removal of organic matter in water

A novel photo-enzyme composite catalyst based on modified carbon nitride was constructed and applied in the removal of antibiotics and phenolic pollutants in water. This composite catalyst (Cyt c/C/CN) has high catalytic activity and stability under acidic or alkaline conditions, which broadens the application range of cytochrome c (Cyt c). In addition, it has A high degradation rate and mineralized rate for sulfadiazine (SDZ) and bisphenol A (BPA). Among them, the degradation and total organic carbon (TOC) removal rate of SDZ were 65.53% and 40.44% respectively, which were much higher than that of pure CN (50.83% and 9.76%). Moreover, the degradation and TOC removal rate of BPA were 72.53% and 44.66%, which were 1.3 times and 2.5 times that of pure CN, respectively. The findings provide insights for designing photo-enzyme coupling systems to efficiently and at a high level remove sulfonamides antibiotics and phenolic agricultural organic pollutants in a simple step.

Impacts of multi-pollutants on sulfonamide antibiotic removal from water matrices using layered double hydroxide sorbents

Remediation of sulfamethoxazole (SMX) present in the aqueous environment requires the development of new advanced wastewater treatment technologies, crucial to reduce the toxicity of such pollutants to the environment, supporting urban water reuse. Continuously synthesised layered double hydroxides (LDH) have been applied as a sorbent material for the removal of SMX from water. No equilibrium uptake of SMX was observed from any water matrix. However, an unusual sorption/release behaviour of SMX was observed in the presence of Mg2Al-NO3-LDH, influenced by the characteristics of the water matrix. A maximum SMX removal percentage of 34.7% was reached within 10 min, from ultrapure water, followed by release of SMX back into solution over the following 24 h. Further, Mg2Al-NO3-LDH is shown to release NO3- into all water matrices. It is proposed that NO3- disrupts the SMX-LDH interactions, resulting in release of SMX from the LDH. No initial SMX sorption was observed onto Mg2Al-NO3-LDH when wastewater effluent was the water matrix, likely due to competition for sorption sites on the LDH with multiple pollutants, including metals and additional anionic nutrients, present in the wastewater. This work illustrates the potential for relationships between the sorbent material and water matrix interactions on pollutant sorption behaviour. In addition, the findings highlight the importance of conducting removal experiments at realistic environmental conditions to ensure development of suitable sorbent materials for pollutant remediation.

Nanoporous Pyrene-Based Metal–Organic Frameworks for Fluorescence Screening and Discrimination of Sulfonamide Antibiotics

Nanoporous Pyrene-Based Metal–Organic Frameworks for Fluorescence Screening and Discrimination of Sulfonamide Antibiotics