Natural attenuation of sulfonamides and metabolites in contaminated groundwater - Review, advantages and challenges of current documentation techniques.

Sulfonamides are applied worldwide as antibiotics. They are emerging contaminants of concern, as their presence in the environment may lead to the spread of antibiotic resistance genes. Sulfonamides are present in groundwater systems, which suggest their persistence under certain conditions, highlighting the importance of understanding natural attenuation processes in groundwater. Biodegradation is an essential process, as degradation of sulfonamides reduces the risk of antibiotic resistance spreading. In this review, natural attenuation, and in particular assessment of biodegradation, is evaluated for sulfonamides in groundwater systems. The current knowledge level on biodegradation is reviewed, and a scientific foundation is built based on sulfonamide degradation processes, pathways, metabolites and toxicity. An overview of bacterial species and related metabolites is provided. The main research effort has focused on aerobic conditions while investigations under anaerobic conditions are lacking. The level of implementation in research is laboratory scale; here we strived to bridge towards field application and assessment, by assessing approaches commonly used in monitored natural attenuation. Methods to document contaminant mass loss are assessed to be applicable for sulfonamides, while the approach is limited by a lack of reference standards for metabolites. Furthermore, additional information is required on relevant metabolites in order to improve risk assessments. Based on the current knowledge on biodegradation, it is suggested to use the presence of substituent-containing metabolites from breakage of the sulfonamide bridge as specific indicators of degradation. Microbial approaches are currently available for assessment of microbial community's capacities, however, more knowledge is required on indigenous bacteria capable of degrading sulfonamides and on the impact of environmental conditions on biodegradation. Compound specific stable isotope analysis shows great potential as an additional in situ method, but further developments are required to analyse for sulfonamides at environmentally relevant levels. Finally, in a monitored natural attenuation scheme it is assessed that approaches are available that can uncover some processes related to the fate of sulfonamides in groundwater systems. Nevertheless, there are still unknowns related to relevant bacteria and metabolites for risk assessment as well as the effect of environmental settings such as redox conditions. Alongside, uncovering the fate of sulfonamides in future research, the applicability of the natural attenuation documentation approaches will advance, and provide a step towards in situ remedial concepts for the frequently detected sulfonamides.

Cooperation among nitrifying microorganisms promotes the irreversible biotransformation of sulfamonomethoxine.

Ammonia-oxidizing microorganisms, including AOA (ammonia-oxidizing archaea), AOB (ammonia-oxidizing bacteria), and Comammox (complete ammonia oxidization) Nitrospira, have been reported to possess the capability for the biotransformation of sulfonamide antibiotics. However, given that nitrifying microorganisms coexist and operate as communities in the nitrification process, it is surprising that there is a scarcity of studies investigating how their interactions would affect the biotransformation of sulfonamide antibiotics. This study aims to investigate the sulfamonomethoxine (SMM) removal efficiency and mechanisms among pure cultures of phylogenetically distinct nitrifiers and their combinations. Our findings revealed that AOA demonstrated the highest SMM removal efficiency and rate among the pure cultures, followed by Comammox Nitrospira, NOB, and AOB. However, the biotransformation of SMM by AOA N. gargensis is reversible, and the removal efficiency significantly decreased from 63.84 % at 167 h to 26.41 % at 807 h. On the contrary, the co-culture of AOA and NOB demonstrated enhanced and irreversible SMM removal efficiency compared to AOA alone. Furthermore, the presence of NOB altered the SMM biotransformation of AOA by metabolizing TP202 differently, possibly resulting from reduced nitrite accumulation. This study offers novel insights into the potential application of nitrifying communities for the removal of sulfonamide antibiotics (SAs) in engineered ecosystems.

Removal of sulfonamides from water by wetland plants: Performance, microbial response and mechanism.

Sulfonamides are widely used in the clinical and animal husbandry industry because of their antibacterial properties and low cost. However, Sulfonamides cannot be fully absorbed by human bodies or animals, 50 %-90 % will be discharged from the bodies, and enter waters and soils through a variety of ways, causing environmental harm. Phytoremediation as a green in situ repair technology has been proven effective in sulfonamides removal, but the underlying mechanisms are still a question that needs to be further studied. In order to explore the relationship between SAs removal and plants (S. validus), root exudates secreted from plants, and microorganisms, the study conducted a series of experiments and used the structural equation model to quantify the pathways of sulfonamides removal in wetland plants. The removal rate of sulfonamides in the plant treatment group (77.6-92 %) was significantly higher than that in the root exudate treatment group (25.7-36.3 %) and water treatment group (16.3-19.6 %). Plant uptake (λ1 = 0.72-0.77) and microbial degradation (λ2 = 0.31-0.38) were the most important pathways for sulfonamides removal. Sulfonamides could be directly removed through the accumulation, adsorption and metabolism of plants. Meanwhile, plants could indirectly remove sulfonamides by promoting microbial degradation. These results will facilitate our understanding of the underlying mechanism and the improvement of sulfonamides removal efficiency in phytoremediation.

The fate of sulfonamides in microenvironments of rape and hot pepper rhizosphere soil system.

Sulfonamides (SAs) in agricultural soils can be degraded in rhizosphere, but can also be taken up by vegetables, which thereby poses human health and ecological risks. A glasshouse experiment was conducted using multi-interlayer rhizoboxes to investigate the fate of three SAs in rape and hot pepper rhizosphere soil systems to examine the relationship between the accumulation and their physicochemical processes. SAs mainly entered pepper shoots in which the accumulation ranged from 0.40 to 30.64 mg kg-1, while SAs were found at high levels in rape roots ranged from 3.01 to 16.62 mg kg-1. The BCFpepper shoot exhibited a strong positive linear relationship with log Dow, while such relationship was not observed between other bioconcentration factors (BCFs) and log Dow. Other than lipophilicity, the dissociation of SAs may also influence the uptake and translocation process. Larger TF and positive correlation with log Dow indicate preferential translocation of pepper SAs. There was a significant (p < 0.05) dissipation gradient of SAs observed away from the vegetable roots. In addition, pepper could uptake more SAs under solo exposure, while rape accumulated more SAs under combined exposure. When SAs applied in mixture, competition between SAs might occur to influence the translocation and dissipation patterns of SAs.

The phloem and xylem structure of plants and the neutral and ionic partitioning of sulfonamides (SAs) influence the uptake and translocation of SAs.A significant (p < 0.05) dissipation gradient of SAs was observed away from the vegetable roots.Combined exposure could promote the correlation between log BCF and log D_ow.

Copper regulates degradation of typical antibiotics by microalgal-fungal consortium in simulated swine wastewater: insights into metabolic routes and dissolved organic matters.

Microalgae-based biotechnology for antibiotics biodegradation in swine wastewater has been receiving an increasing attention. In this study, microalgae and fungi co-cultivation system, regulated by copper (Cu(II)), was investigated in terms of nutrients and sulfonamides degradation in simulated swine wastewater. Results showed that the removal of ammonium nitrogen (NH4+-N), total nitrogen (TN), total phosphorus (TP) and chemical oxygen demand (COD) by microalgal-fungal consortium increased under 0.1-0.5 mg/L Cu(II) with the highest removal efficiency of 79.19%, 76.18%, 93.93% and 93.46%, respectively. The addition of Cu(II) (0-0.5 mg/L) enhanced the removal of sulfamonomethoxine (SMM), sulfamethoxazole (SMX) and sulfamethazine (SMZ) from 49.05% to 58.76%, from 59.31% to 63.51%, and from 37.51% to 63.9%, respectively, and the main removal mechanism was found to be biodegradation. Biodegradation followed a pseudo-first-order model with variable half-lives (10.12 to 15.51 days for SMM, 9.01 to 10.88 days for SMX, and 8.74 to 12.85 days for SMZ). Through mass spectrometry analysis, metabolites and intermediates of sulfonamides were accordingly identified, suggesting that the degradation routes were involved with hydroxylation, deamination, oxidation, de-sulfonation and bond cleavage. Dissolved organic matters released by microalgal-fungal consortium were induced by Cu(II). Fulvic acid-like and protein-like substances were bound to Cu(II), reducing its concentration and thus mitigating the organismal damage to microorganisms. These findings drew an insightful understanding of microalgal-fungal consortium for sulfonamides remediation by Cu(II) regulation in simulated swine wastewater.

Interactions between sulfonamide homologues and glycosyltransferase induced metabolic disorders in rice (Oryza sativa L.).

Sulfadiazine and its derivatives (sulfonamides, SAs) could induce distinct biotoxic, metabolic and physiological abnormalities, potentially due to their subtle structural differences. This study conducted an in-depth investigation on the interactions between SA homologues, i.e. sulfadiazine (SD), sulfamerazine (SD1), and sulfamethazine (SD2), and the key metabolic enzyme (glycosyltransferase, GT) in rice (Oryza sativa L.). Untargeted screening of SA metabolites revealed that GT-catalyzed glycosylation was the primary transformation pathway of SAs in rice. Molecular docking identified that the binding sites of SAs on GT (D0TZD6) were responsible for transferring sugar moiety to synthesize polysaccharides and detoxify SAs. Specifically, amino acids in the GT-binding cavity (e.g., GLY487 and CYS486) formed stable hydrogen bonds with SAs (e.g., the sulfonamide group of SD). Molecular dynamics simulations revealed that SAs induced conformational changes in GT ligand binding domain, which was supported by the significantly decreased GT activity and gene expression level. As evidenced by proteomics and metabolomics, SAs inhibited the transfer and synthesis of sugar but stimulated sugar decomposition in rice leaves, leading to the accumulation of mono- and disaccharides in rice leaves. While the differences in the increased sugar content by SD (24.3%, compared with control), SD1 (11.1%), and SD2 (6.24%) can be attributed to their number of methyl groups (0, 1, 2, respectively), which determined the steric hindrance and hydrogen bonds formation with GT. This study suggested that the disturbances on crop sugar metabolism by homologues contaminants are determined by the interaction between the contaminants and the target enzyme, and are greatly dependent on the steric hindrance effects contributed by their side chains. The results are of importance to identify priority pollutants and ensure crop quality in contaminated fields.

Gallic Acid Restores the Sulfonamide Sensitivity of Multidrug-Resistant Streptococcus suis via Polypharmaceology Mechanism.

Due to the large amount of antibiotics used for human therapy, agriculture, and even aquaculture, the emergence of multidrug-resistant Streptococcus suis (S. suis) led to serious public health threats. Antibiotic-assisted strategies have emerged as a promising approach to alleviate this crisis. Here, the polyphenolic compound gallic acid was found to enhance sulfonamides against multidrug-resistant S. suis. Mechanistic analysis revealed that gallic acid effectively disrupts the integrity and function of the cytoplasmic membrane by dissipating the proton motive force of bacteria. Moreover, we found that gallic acid regulates the expression of dihydrofolate reductase, which in turn inhibits tetrahydrofolate synthesis. As a result of polypharmacology, gallic acid can fully restore sulfadiazine sodium activity in the animal infection model without any drug resistances. Our findings provide an insightful view into the threats of antibiotic resistance. It could become a promising strategy to resolve this crisis.

Sulfonamide-metabolizing microorganisms and mechanisms in antibiotic-contaminated wetland sediments revealed by stable isotope probing and metagenomics.

Sulfonamide (SA) antibiotics are ubiquitous pollutants in livestock breeding and aquaculture wastewaters, which increases the propagation of antibiotic resistance genes. Microbes with the ability to degrade SA play important roles in SA dissipation, but their diversity and the degradation mechanism in the field remain unclear. In the present study, we employed DNA-stable isotope probing (SIP) combined with metagenomics to explore the active microorganisms and mechanisms of SA biodegradation in antibiotic-contaminated wetland sediments. DNA-SIP revealed various SA-assimilating bacteria dominated by members of Proteobacteria, such as Bradyrhizobium, Gemmatimonas, and unclassified Burkholderiaceae. Both sulfadiazine and sulfamethoxazole were dissipated mainly through the initial ipso-hydroxylation, and were driven by similar microbes. sadA gene, which encodes an NADH-dependent monooxygenase, was enriched in the 13C heavy DNA, confirming its catalytic capacity for the initial ipso-hydroxylation of SA in sediments. In addition, some genes encoding dioxygenases were also proposed to participate in SA hydroxylation and aromatic ring cleavage based on metagenomics analysis, which might play an important role in SA metabolism in the sediment ecosystem when Proteobacteria was the dominant active bacteria. Our work elucidates the ecological roles of uncultured microorganisms in their natural habitats and gives a deeper understanding of in-situ SA biodegradation mechanisms.

Enhanced sulfonamides removal via microalgae-bacteria consortium via co-substrate supplementation.

Both co-cultivation and co-substrate addition strategies have exhibited massive potential in microalgae-based antibiotic bioremediation. In this study, glucose and sodium acetate were employed as co-substrate in the cultivation of microalgae-bacteria consortium for enhanced sulfadiazine (SDZ) and sulfamethoxazole (SMX) removal. Glucose demonstrated a two-fold increase in biomass production with a maximum specific growth rate of 0.63 ± 0.01 d-1 compared with sodium acetate. The supplementation of co-substrate enhanced the degradation of SDZ significantly up to 703 ± 18% for sodium acetate and 290 ± 22% for glucose, but had almost no effect on SMX. The activities of antioxidant enzymes, including peroxidase, superoxide dismutase and catalase decreased with co-substrate supplementation. Chlorophyll a was associated with protection against sulfonamides and chlorophyll b might contribute to SDZ degradation. The addition of co-substrates influenced bacterial community structure greatly. Glucose enhanced the relative abundance of Proteobacteria, while sodium acetate improved the relative abundance of Bacteroidetes significantly.

The in vivo and vitro degradation of sulfonamides in wetland plants reducing phytotoxicity and environmental pollution.

Aquatic plants can be used for in situ remediation of water-borne pharmaceutical compounds; however, such information and that of the potential risks of metabolites released into the environment are limited. This study determined the capacity of Canna indica and Acorus calamus used in the remediation of water-borne sulfonamides (SA). The tolerance, removal, accumulation, and biotransformation of various water-borne SAs were investigated in vivo by exposing plants to SA solutions (50 µg/L and 500 µg/L). After 28 days, C. indica removed more SAs (89.3-97.8%) than A. calamus (12.8-84.6%) and non-planted systems (8.0-69.3%). The SA removal results, except from the A. calamus system with 500 µg/L SA, fit the first-order kinetics model. The estimated half-lives of all SAs were 3-40 h and 2-60 h in the C. indica and A. calamus systems, respectively. In vivo biotransformation and rhizosphere degradation were the major phyto-removal mechanisms, constituting 24.9-81.1% and 0.0-37.1% of all SAs in the C. indica and A. calamus systems, respectively. SA acetyl metabolites were detected only in plant tissues supporting evidence for plant metabolic processes without risk into the environment. SA metabolism including oxidation, methylation, and conjugation via acetylation was potentially beneficial to accumulation and tolerate stress of antibiotic. Canna indica was more suitable for cleaning SA. Our findings better clarify the potential and low risks of phytoremediation in antibiotic-contaminated waters.

Voltammetric Determination of Binding Constant and Stoichiometry of Albumin (Human, Bovine, Ovine)-Drug Complexes.

The parameters characterizing the formation of complexes with albumin (in particular, human serum albumin (HSA)) are fundamental for the characterization of a drug for commercialization purposes and for the determination of common pharmacokinetic parameters. Electrochemical methods appear particularly attractive for the determination of the complexation constant, complex stoichiometry, and percentage of free/bound drug, due to the ease of operation and the wide availability. In this article, we propose an electrochemical method based on differential pulse voltammetry for the determination of albumin-drug interaction parameters, including the replacement of the drug-albumin adduct by a competitive compound, sulfanilamide. The formation of either single or multiple complexes between the considered drug and albumin has been considered. Typically, the method operates with a glassy carbon electrode in NaCl 0.9% as the supporting electrolyte.

Biosorption behavior and mechanism of sulfonamide antibiotics in aqueous solution on extracellular polymeric substances extracted from Klebsiella sp. J1.

The pollution of sulfonamide antibiotics in aqueous system has attracted an increasing attention, however, interactions between the effective biomaterial and sulfonamide antibiotics are not clear. In this study, adsorption capacity and interaction mechanism of EPS from Klebsiella sp. J1 and sulfonamide antibiotics were investigated. The biosorption efficiency of EPS were 70.0%, 55.1%, 51.8%, and 46.7% for SMX, SM1, SM2, and SDZ, respectively. Qualitative and quantitative analysis displayed the almost consistent adsorption mechanism for four sulfonamides on EPS. The adsorption behavior could be described by Langmuir, Freundlich isotherms and the pseudo-second-order kinetics model. Model parameters indicated the chemisorption was the major adsorption type responsible for the adsorption process and demonstrated a good adsorption capacity of EPS for sulfonamides, also confirmed by the SEM observation. Interestingly, 3D-EEM suggested that the driving force was mainly from the hydrophobic interaction of tryptophan and tyrosine during the binding process of EPS and sulfonamides.