- 1Guangxi Key Laboratory of Environmental Pollution Control Theory and Technology, Guilin University of Technology, Guilin, China
- 2Engineering Research Center of Watershed Protection and Green Development, University of Guangxi, Guilin University of Technology, Guilin, China
- 3Guangxi Engineering Research Center of Comprehensive Treatment for Agricultural Non-Point Source Pollution, Guilin University of Technology, Guilin, China
- 4Modern Industry College of Ecology and Environmental Protection, Guilin University of Technology, Guilin, China
- 5Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area, Guilin University of Technology, Guilin, China
Antibiotics and Hg, as common environmental contaminants, are prevalent in different environmental media, including water and soil. Their collective pollution presents potential hazards to ecosystems and human health. This research comprehensively examines the present state of antibiotic-Hg co-contamination and their interaction mechanisms. Studies demonstrate that their interactions are intricate, encompassing both chemical and biological dimensions. Antibiotic molecular structures, such as carboxyl and amino groups, can chemically create chelating compounds with Hg, influencing its adsorption-desorption dynamics and bioavailability. Specific antibiotics (e.g., methl-containing antibiotics) may provide methyl groups during breakdown, thus facilitating Hg methylation and producing highly toxic methylmercury (MeHg). Antibiotics biologically modify microbial community structures, consequently affecting the equilibrium between the biological methylation and demethylation of Hg. Moreover, antibiotic exposure may influence Hg metabolism in organisms and is linked to the co-selection of Hg resistance genes (MRGs) and antibiotic resistance genes (ARGs), hence exacerbating environmental concerns. The present comprehension of the mechanisms by which antibiotics influence Hg transport, transformation, and toxicity is contentious and inadequate, especially in specialized ecosystems such as wetlands. Consequently, a thorough examination of their interconnections is crucial to establish a scientific foundation for evaluating and managing combined pollution hazards.
1 Introduction
Global population expansion and expanding economic activity are intensifying the pressure of human activities on the environment. Among other new contaminants, antibiotics and heavy metals especially Hg have attracted considerable attention from researchers globally due to their multiple sources, intricate ecosystem dynamics, and possible ecotoxicological effects. Antibiotics, essential compounds in contemporary medicine and livestock management, demonstrate a continuous rise in environmental residues. They arise not only from human and animal waste but also from extensive agricultural practices (including livestock and poultry farming, aquaculture) and industrial effluent discharges (Jiping et al., 2022), leading to their pervasive presence in surface water, groundwater, soil, sediments, and even drinking water sources. Antibiotics display a variety of chemical structures, generally categorized by their fundamental frameworks into macrolides (MLs), β-lactams (BLs), tetracyclines (TCs), quinolones (QNs), and more classes. These structural variations impart unique physicochemical characteristics and environmental interactions.
Mercury, an extremely hazardous heavy metal, has consistently raised concerns regarding environmental pollution. Its extreme lipophilicity and potential for bioaccumulation, especially in organic forms such as MeHg, pose significant long-term risks to ecosystems and human health. Hg emissions arise from various sources, including industrial manufacturing, fossil fuel burning, and natural recycling processes. In diverse environmental media, especially wetland habitats abundant in organic matter and specialized microbes, Hg experiences intricate biogeochemical changes. The synthesis of MeHg and its bioaccumulation effects are significant sources of environmental and health hazards (Budnik and Casteleyn, 2019). The distinctive redox conditions and microbial populations of wetlands render them potential sinks and transformation sites for Hg, hence exacerbating the risks associated with MeHg.
The amalgamation of antibiotic and heavy metal contamination, particularly the interaction between antibiotics and Hg, has emerged as a significant field of study. The molecular structure of antibiotics, including their functional groups, may engage in chelation interactions with Hg ions, therefore modifying the ambient speciation, movement and transformation rates, and bioavailability of Hg. Initial research indicates that antibiotics may impact microbial metabolic pathways, either facilitating or obstructing Hg methylation activities, thereby influencing MeHg synthesis. Conversely, the presence of Hg may modify antibiotic breakdown rates or the susceptibility of microbial communities to particular antibiotics. This complexity complicates the correct assessment of the genuine threats posed by combined pollution to ecosystems and species. Although considerable study has been conducted on individual antibiotic or Hg pollution, comprehension of their combined environmental behavior and possible synergistic consequences is still inadequate. This disparity is especially evident in ecosystems that are very susceptible to external perturbations, such as wetlands. The distinctive groundwater recharge patterns, exposed surfaces, hence posing considerable risks to local water supplies and ecological integrity (You et al., 2020).
The field lacks a unified assessment framework capable of simultaneously weighing technical efficiency, cost-effectiveness and environmental impact (Dou et al., 2025). Acquiring an in-depth comprehension of the migration and transformation mechanisms, interaction patterns, and extensive effects of antibiotics and Hg on ecosystems and human health in the specific context of wetlands is essential for formulating regional environmental protection and risk management strategies. This study intends to carefully analyze and synthesize available literature, concentrating on the present pollution state and the migration/transformation mechanisms of antibiotics and Hg in the environment. This study precisely analyzes the cumulative pollution impacts on ecosystems like Karst wetlands and investigates prospective research avenues, offering a scientific foundation for tackling this escalating environmental issue.
2 Types of antibiotics
Antibiotics are categorized into various classes according to their chemical structure, including MLs, BLs, TCs, QNs, fluoroquinolones (FQs), sulfonamides (SAs), and penicillins, as shown in Figure 1. The durability of antibiotics in various environments, including water, soil, and air, is contingent upon their physicochemical properties: octanol/water partition coefficient (Kow), distribution coefficient (Kd), dissociation constant (pKa), vapor pressure, and Henry’s law constant (KH). Compared to other antibiotics, FQs and TCs have greater stability, enabling prolonged environmental persistence and subsequent accumulation at elevated quantities (Kim et al., 2024). Similarly, CIP and ERY exhibit resistance to degradation owing to the lack of a BL structure. Among antibiotics, FQs and SAs are the most perilous in the environment; nonetheless, photolysis may transpire for these compounds (Qiulian et al., 2021). The environmental effects of these two antibiotics (FQs and SAs) encompass nitrification and denitrification processes, resulting in the accumulation of nitrites and nitrogen oxides in aquatic ecosystems.
2.1 MLs (macrolides)
Macrolides comprise a lactone ring with 12–16 carbon atoms, modified by one or more amino sugars (Li et al., 2022a; Nagao et al., 2025). This group is characterized by lipophilicity, low aqueous solubility, and weak acidity. MLs are generally bacteriostatic, although certain variants may have bactericidal properties at elevated dosages. They are frequently utilized to address respiratory, dermatological, and soft tissue infections. A study projects that global antibiotic usage in humans and animals would rise from 42.3 billion specified daily doses in 2015 to 128 billion by 2030 (Klein et al., 2018). Moreover, owing to their diminished absorption and metabolism rates, antibiotics are eliminated as unaltered and active metabolites. The substantial use of MLs in human medicine, agriculture, and aquaculture results in their environmental discharge alongside their metabolites.
2.2 SAs (sulfonamides)
Sulfonamides include an aniline sulfonamide functional group. This group exhibits amphiphilicity. SAs continue to be extensively utilized in contemporary animal husbandry (Dai et al., 2025). In comparison to other antibiotics, they demonstrate significant hydrophilicity and comparatively low adsorption capability to solid matrices, resulting in the great mobility and transformability of SAs and their metabolites in the environment (Kodesova et al., 2016). Substances and their metabolites are extensively disseminated in aquatic ecosystems, agricultural soils, and river sediments. Upon distribution into the environment, SAs may negatively affect ecosystems by modifying microbial populations or producing antibiotic-resistant bacteria (Chen et al., 2022; Hu et al., 2023). ARGs are widespread in global environmental contexts and pose a significant threat to public health in the 21st century.
2.3 TCs (tetracyclines)
Tetracyclines are principal antibiotics utilized in veterinary and human health, agriculture, and as food additives to enhance animal growth. TCs compounds generally consist of tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC), and doxycycline (DXC). These substances possess analogous chemical characteristics. Their elevated water solubility and diminished octanol-water partition coefficient signify that TCs are hydrophilic, amphiphilic, and biodegradable antibiotics. They exhibit instability in alkaline circumstances but demonstrate relative stability in acidic situations (Tadic et al., 2021). These drugs present considerable environmental concerns and substantial dangers to human health. Traditional wastewater treatment fails to completely eradicate these micropollutants, with documented removal efficiency for TCs in treatment facilities varying between 12% and 85.4% (Batt et al., 2007). Research demonstrates that merely a minor percentage of TCs is digested or absorbed in vivo, whereas up to 75% is generally excreted in its active state (Tutus et al., 2025). TCs often contaminate surface water, groundwater, potable water, wastewater, sediments, and sludge, hence damaging adjacent habitats and upsetting ecological equilibrium (Lundstrom et al., 2016).
2.4 QNs (quinolones)
Quinolones are extensively utilized for treating infections in both humans and animals. They are distinguished by their lipophilicity and resilience to acid hydrolysis, alkalinity, elevated temperatures, and UV light damage. Quinolones are applied in diverse domains, including human and veterinary medicine, as well as growth promotion in livestock and aquaculture sectors. They infiltrate aquatic ecosystems by untreated human and animal effluent or aquaculture products. QNs have been widely utilized in the aquaculture sector throughout several regions in China for a prolonged duration (Yan et al., 2013; Zhang et al., 2017a; Li et al., 2018a; Yin, 2021). In comparison to other antibiotics, such as cephalosporins, TCs, QNs present advantages including affordability, potent antibacterial efficacy, minimal toxicity and side effects, and ease of degradability. The ensuing bans on medications such as chloramphenicol and ERY by pertinent national agencies have resulted to an increasing usage rate of QNs in aquaculture.
3 Background on antibiotic and Hg pollution
3.1 Antibiotic pollution in different aquatic environments
In the last 10 years, antibiotics such as SAs, TCs, QNs, MLs, and BLs have been identified in several environmental matrices in domestic and international (Li et al., 2017; Zhang et al., 2017b; Wang et al., 2019). Numerous research have assessed the present condition of antibiotics in various environmental media throughout domestic and international (Xue et al., 2013; Yan et al., 2013; Tong et al., 2017; Li et al., 2018b; Huang et al., 2019; Mohebi et al., 2020). Jiao et al. conducted a review of antibiotic degradation and distribution in agricultural soils and aquatic ecosystems during the preceding 3 years (Jia et al., 2023). Sulfonamides were the most commonly identified antibiotics in agricultural soils and surface waters, but TCs demonstrated the greatest median values in agricultural soils (7.74 μg/kg) and surface waters (46.4 ng/L). Huang et al. aggregated more than 170 studies on the presence of antibiotics in Chinese environmental media. Of the 110 antibiotics examined, 28 were found to be pervasive across all Chinese environmental media, with TCs and QNs being the most prevalent antibiotics in every habitat (Huang et al., 2020). Median antibiotic concentrations in marine ecosystems surpassed those in other aquatic habitats. Animal farms and sewage treatment facilities functioned as principal sources, whilst surface water and sediments acted as significant sinks. Zeinab et al. (Zeinab et al., 2022) found that the antibiotics with the highest concentrations in Lake Michigan sediments were azithromycin (147.28 ng/g) and clarithromycin (67.66 ng/g), while the concentration of azithromycin in the water body was 12.5 ng/L. The concentration of amoxicillin (a penicillin antibiotic) in a lake in Turkey is 1.1–1.15 ng/L.
Numerous antibiotics have been identified in the surface water and sediments of significant Chinese rivers (Xu et al., 2013; Zhang et al., 2017a; Yin, 2021; Chen et al., 2022; Jingli et al., 2022). Research has evaluated the distribution of antibiotic pollution in China’s seven principal rivers (Pearl River, Yangtze River, Huai River, Yellow River, Hai River, Liao River, and Songhua River) and four seas (South China Sea, East China Sea, Yellow Sea, and Bohai Sea). Evaluating the possible environmental hazards of antibiotics in prominent Chinese rivers necessitates a comparison of toxicity to standard indicator organisms, such as algae, plants, invertebrates, and fish (Li et al., 2018b). The majority of studies concerning environmental antibiotic residues concentrate on surface water, sediments, sewage treatment facilities, livestock farms, and soil; however, investigations into wetland waters are scarce.
3.2 Distribution of antibiotic pollution in wetland environments
Studies reveal extensive antibiotic prevalence in river systems in Southwest China. In Kaili, 37 of 43 investigated antibiotics were detected, with MLs and quinolones QNs particularly prominent. Concentrations were significantly higher during the dry season, though spatial distribution was strongly influenced by anthropogenic activities (Zou et al., 2018). Research in Shanghai’s Pudong New Area indicates that antibiotic concentrations are higher during the dry season than the wet season, primarily attributed to reduced water dilution and diminished river self-purification capacity (Pan et al., 2020). Antibiotic concentrations were significantly higher in the dry season than the wet season (p < 0.05). Wet season precipitation accounts for 70% of annual rainfall, leading to lower antibiotic concentrations in rivers (Kuang et al., 2020). Reduced microbial activity and diminished light intensity under low-temperature conditions hinder antibiotic biodegradation and photodegradation. Studies on Bangladesh’s Buriganga River indicate both the number of detected antibiotics and overall concentrations are higher during the dry season (February) than the wet season (August) (Salma et al., 2024). Research on Baiyang Lake shows most antibiotics exhibit higher concentrations during the dry season, with tributary estuaries displaying greater concentrations than the lake itself, demonstrating dilution effects (Deng et al., 2025; Martins et al., 2025). Guo et al. identified 27 antibiotics in Caohai, a Karst plateau wetland within the Yangtze River Basin, with ciprofloxacin (CIP), oxytetracycline (OTC), acetylsulfadiazine (ASMZ), norfloxacin (NOR), and florfenicol (FF) most prevalent. Household sewage and livestock effluent were identified as primary contamination sources (Guo et al., 2022). Notably, the ecological risks of antibiotic combinations exceeded those of individual compounds. Furthermore, additional research with more frequent monitoring is necessary to evaluate temporal fluctuations, which is especially vital for dynamic wetland systems. Antibiotic contamination in karst environments has emerged as a global concern. Studies in Germany’s Gallusquelle wetland spring detected 11 antibiotic resistance genes (ARGs) across 6 antibiotic classes, with contamination levels strongly correlated with heavy rainfall events and combined sewer overflow from urban infrastructure located 9 km from the spring (Stange and Tiehm, 2020). Romanian wetland springs showed that over half were contaminated with fecal bacteria and pathogens, with elevated levels of sulfonamide and macrolide resistance genes transmitted primarily through mobile genetic elements. The interconnected nature of wetland conduit networks facilitates rapid contaminant transport across extensive areas, complicating remediation efforts and requiring enhanced monitoring protocols and transboundary management strategies (Edina et al., 2023).
3.3 Combined pollution from antibiotics and heavy metals
Antibiotics are extensively utilized in agriculture, aquaculture, and livestock management. Antibiotic residues endure in environmental media for prolonged durations, with bacteria and microorganisms harboring MRGS threatening ecosystems and human health (Zhang et al., 2017b; Yin, 2021; Jia et al., 2023). Heavy metals can migrate through environmental media and be transmitted throughout food chains, presenting potential hazards to human health and ecosystems (Wang et al., 2013; Li et al., 2020). Although trace quantities of heavy metals are vital for the growth of plants and animals, higher concentrations are detrimental to the environment and living creatures. These poisons can accumulate and amplify, inflicting damage via food chain transmission (Yi et al., 2011; Qin and Tao, 2022). Antibiotics and heavy metals often coexist in environmental media, resulting in combined antibiotic-heavy metal contamination. Furthermore, antibiotic-heavy metal combos demonstrate increased toxicity. Antibiotics and heavy metals are common environmental contaminants that frequently coexist and interact in environmental media (Imchen et al., 2018; Han et al., 2021). Consequently, evaluating the toxicity of their cumulative contamination is essential.
Studies demonstrate that synergistic pollutants possess greater toxicity than singular contaminants (Kaur et al., 2018). The research revealed that the combined action of antibiotics and heavy metals significantly exceeded the effects of single antibiotic exposure in terms of its impact on the functional diversity of soil microbial communities (Tang et al., 2020). Effects of different antibiotics on Hg Behavior as shown in Table 1. Research investigating the impact of the antibiotic flumequine (FLQ) on fish gut microbiota and its role in Hg biotransformation and bioaccumulation in tilapia demonstrated a marked decrease in methylation activity within the gut microbiota post-FLQ administration. The antibiotic significantly modified intestinal microbial populations, thereby enhancing the likelihood for MeHg buildup in fish (Bingxin et al., 2022). Enhanced fertilization, feed additives, and extended farming periods have significantly elevated concentrations of compound pollutants in soil and water (Wu et al., 2013). Consequently, increased focus should be allocated to the concurrent contamination of heavy metals and antibiotics. The aforementioned research indicated that Hg represent a substantial share of pollutants at polluted sites and should be prioritized for regulation. The precise mechanisms by which Hg and antibiotics interact in environmental contexts are not well understood, warranting additional academic research. Further research is necessary to determine if antibiotic exposure affects Hg methylation processes and whether antibiotics exacerbate or alleviate the toxicity of MeHg.
4 Interactions affecting methylation and demethylation
In natural environments, Hg predominantly occurs as inorganic Hg (Hg0, Hg, Hg2+) and organic Hg (CH3-Hg+) (Li et al., 2008; Zhang and Hsu-Kim, 2010; Wickliffe et al., 2021). Wetlands, essential for Hg biogeochemical cycling (Malczyk and Branfireun, 2015), are rich in dissolved organic matter (DOM), which facilitates stable Hg-thiol complexation (Slowey, 2010; Henneberry et al., 2011; Graham et al., 2012). Consequently, wetlands function as Hg sinks, absorbing external Hg from atmospheric deposition and runoff (Selvendiran et al., 2008a; Selvendiran et al., 2008b; Guentzel, 2009; Haynes et al., 2017), as shown in Figure 2. However, wetland conditions also promote microbial Hg transformation to MeHg, which biomagnifies through aquatic food chains into fish, seafood, and rice—the primary human exposure pathways (Li et al., 2008; Qiu et al., 2008; Han et al., 2019; Wang et al., 2021; Wickliffe et al., 2021).
Methylmercury undergoes demethylation through biotic and abiotic processes, forming inorganic mercury Hg(II) (Pak and Bartha, 1998; Zhang and Hsu-Kim, 2010). Hg(II) may further be converted to elemental mercury Hg0 via reduction processes (Lu et al., 2016; Lu et al., 2017; Jiping et al., 2022). The concurrent occurrence of methylation and demethylation processes in the environment jointly regulates the overall formation and biological accumulation of methylmercury. While abiotic Hg methylation is inefficient, biogenic methylation by sulfate-reducing bacteria (SRB) dominates in anaerobic wetland zones. MeHg degradation occurs primarily through photodegradation in surface waters (Poste et al., 2015). Where DOM plays dual roles: directly facilitating photodemethylation via MeHg-thiol complexation and intramolecular electron transfer, or indirectly through reactive oxygen species generation (Zhang et al., 2018). Nonetheless, agreement is still lacking concerning the processes by which DOM facilitates the breakdown of MeHg.
4.1 Complexation and chelation mechanisms
Antibiotics having numerous functional groups, including carboxyl, hydroxyl, amino, and heterocyclic rings, or electron-donating atoms in their chemical structures, may engage in synergistic, antagonistic, or additive complexation interactions with Hg. The complexation capacity is contingent upon the type of antibiotic and the properties of Hg (Mahbub et al., 2020). The increased quantity and diversity of electron-rich groups (e.g., N, O) in an antibiotic enhance its capacity for Hg-chelation. Nevertheless, an increase in functional groups may augment steric hindrance, thereby diminishing chelation efficiency (Ben Miloud et al., 2021).
Prior research has shown that the incorporation of suitable functional groups can significantly improve the efficacy of Hg adsorbents (Aguila et al., 2017; Huang et al., 2017; Li et al., 2019; Zhao et al., 2019; Hernandez et al., 2020; Li et al., 2021). Owing to the differing affinities of functional groups for heavy metal ions, certain functional groups can enhance both adsorption capacity and selectivity. Researchers have indicated that the sulfhydryl group functions as a highly efficient adsorption site for Hg (Leus et al., 2017; Ballav et al., 2018; Zhao et al., 2019). Under elevated pH circumstances, sulfhydryl groups exhibit instability and are susceptible to oxidation, resulting in the formation of disulfide bonds (Monahan et al., 1995; Choi et al., 2020). Carboxylate groups exhibit enhanced stability and generally coordinate with metal ions in three manners: a single oxygen atom complexes with one metal ion, each oxygen atom binds to an individual metal ion, or two oxygen atoms coordinate with a single metal ion to create a more stable chelate complex. The necessity for more systematic inquiry arises to determine if antibiotic compounds having sulfhydryl, carboxylate, and carboxyl groups demonstrate comparably high adsorption effectiveness.
Wang et al. (2023) experimental findings indicate that polypyrrolidone carboxylates (PPDCBAs) with phenyl carboxyl groups has significant adsorption capacity for the effective and selective removal of Hg(II) from aqueous solutions. The incorporation of carboxyl groups and steric hindrance in PPDCBAs provides exceptional adsorption selectivity for Hg(II). Moreover, PPDCBAs demonstrate increased affinity as they form complexes with heavy metals and carboxyl groups. Buyuktiryaki et al. (2007) synthesized imprinted microspheres utilizing methylmercury-methacryloyl-I-pyridoxal (MM-MAC) and ethylene glycol dimethacrylate (EDMA). Vibrational peaks signify chelation between sulfhydryl and MeHg within the polymer cavity. The adsorption capacity exhibited a linear rise throughout the initial 50 min at pH 7. Comprehensive investigations are necessary to clarify the adsorption-desorption mechanisms of Hg or MeHg at particular structural locations inside the antibiotics.
4.2 The role of microbial regulation in mercury transformation
The ingestion of fish and rice is predominantly acknowledged as the principal route for Hg bioaccumulation. MeHg, once ingested, is taken into the bloodstream and conveyed to target tissues, such as the brain and developing fetuses. The majority of MeHg is eliminated from the liver into bile, subsequently entering the enterohepatic circulation. This cycle facilitates the biomagnification of MeHg by enabling the metal to re-enter systemic circulation. As much as 95% of ingested MeHg is eventually eliminated through feces, while the remaining is excreted in urine as inorganic Hg (Rand and Caito, 2019). MeHg infiltrates creatures from natural habitats, including seas, lakes, and soil, leading to bioaccumulation within food chains and heightening hazards of human exposure. Nonetheless, the metabolic pathways of MeHg in animals remain predominantly unexplored. Removing MeHg from the body necessitates demethylation; however, the chemical link between carbon and Hg is challenging to sever (Zhang and Hsu-Kim, 2010).
In most freshwater environments, anaerobic bacteria proliferate in anoxic zones, with sediment and planktonic biofilms potentially serving as primary producers of methylmercury (Neal-Walthall et al., 2022), as shown in Table 2 (Zhao et al., 2024a). Sulfate-reducing bacteria (SRB) and associated microbes mediate inorganic Hg methylation even in oxygenated lake waters (Feng et al., 2022). Liu et al. revealed complex dynamics in anoxic mangrove sediments: while SRB act as principal methylating agents, organic matter diagenesis simultaneously accelerates MeHg breakdown. This enhanced degradation results from sulfide production during organic matter decomposition, which immobilizes inorganic Hg and impedes methylation—paradoxically contrasting with SRB’s methylation-promoting role (Jingli et al., 2022). The mechanisms and reactions facilitating Hg2+ biomethylation in saline settings may vary from those in freshwater (Regnell and Watras, 2019), MeHg is synthesized by anaerobic bacteria in freshwater environments (Lin et al., 2021). The potential of anaerobic bacteria in the oceanic anaerobic zone (ODZ) as a substantial source of MeHg is currently uncertain. Research on cultivation and microbial community assessment in the equatorial Pacific oxygen minimum zone revealed an absence of sulfate- or iron-reducing bacteria, indicating that anaerobic bacteria in the marine oxygen minimum zone do not significantly contribute to MeHg production in the examined area (Malcolm et al., 2010). Tetracycline antibiotics in marine/estuarine sediments can generate methylmercury (MeHg) both directly through their own structures as abiotic methyl donors and indirectly by significantly stimulating the biogenic methylation activity of sulfate-reducing bacteria through the release of methyl/carbon sources during degradation. This results in a net increase in MeHg production several times greater than that attributable to mere “microbial activity regulation” (Liang et al., 2018). Wetland sediments, characterized by anoxic conditions and bioavailable carbon, facilitate microbial Hg methylation and MeHg production. However, the roles of SRBs and anaerobic microorganisms in wetland Hg biogeochemistry require further investigation to assess MeHg production dynamics and human exposure risks.
The impact of microbes on MeHg toxicity may surpass mere demethylation. The gut microbiota presumably influence neurotransmitters through the gut-brain axis (Abushamat, 1993), potentially exacerbating MeHg neurotoxicity via many routes. Subsequent research may clarify the relationships between MeHg and the gut flora (Bridges et al., 2018; Dempsey et al., 2019). Under intricate pollution settings, heavy metal stress facilitates environment-mediated plasmid conjugative transfer via cellular damage, hence expediting the dissemination and proliferation of resistance genes (Wang et al., 2020). The previously reported antibiotic usage may enhance MeHg bioaccumulation in fish (Bingxin et al., 2022).
5 Antibiotic-mercury interactions
5.1 Mechanism of action of antibiotics and mercury
Literature indicates that the addition of antibiotics leads to the dissolution of mercury (Liang et al., 2018), as the complexes formed between antibiotics and Hg2+ exhibit higher solubility than Hg2+ alone. The complexation of antibiotics with metal ions depends on the number of electron-donating functional groups (e.g., -OH and -C=O) and the electronegativity of the metal ion (Tommasino et al., 2011). These electron-rich functional groups stabilize by complexing with highly polarized transition metals (Pulicharla et al., 2017). The metal’s positive charge partially shares with the negative charge of electron-donating atoms in TC/OTC, and electrons delocalized on the shared atoms (the chelate ring) stabilize the high electron density of TC/OTC. The electron-donating functional groups in TC and OTC are more electron-rich than those in other antibiotics, such as quinolones and sulfonamides. Consequently, TC and OTC appear to exhibit a tendency to form complexes with metals. Another factor influencing antibiotic-metal complexation is the nature of the metal ion, specifically its ionic radius and electronegativity. Metal ions with higher electronegativity are more prone to complexation. Hg2+ exhibits an electronegativity of 2.0, surpassing Ni2+ (1.91), Cu2+ (1.9), and Fe3+ (1.83). This indicates Hg2+ exhibits a particularly strong affinity for antibiotics. Experimental results by Liang et al. demonstrate significantly elevated methylmercury concentrations in sediments at the conclusion of TC or TOC treatment, suggesting antibiotic use may promote methylmercury formation in sediments. As described above, antibiotics complex with Hg2+ to form antibiotic radicals and Hg2+. After electron donation, the antibiotic radicals remain active. Consequently, antibiotics undergo further degradation, with the -CH3 group potentially reacting with Hg0 to form CH3-Hg. This occurs because Hg0 readily forms CH3Hg+ compared to Hg2+ (Liang et al., 2018). Previous studies have demonstrated that heavily contaminated sediments typically harbor microbial populations actively degrading methylmercury via Mer denitrification. Oxidative demethylation also occurs in heavily polluted sediments, whereas it dominates in less contaminated sediments (Zhao et al., 2024a). Marvin-DiPasquale M et al. found that mercury-resistant bacteria possessing Mer operon genes can dominate the demethylation process, a capability widely present in nature (Marvin-Diasquale et al., 2000). In broad-spectrum mercury-tolerant bacteria, the mer-B gene encodes an organomercury hydrolase that degrades methylmercury into CH4 and Hg(II), while the mer-A gene encodes a mercury reductase that further reduces Hg(II) to the volatile element Hg0 (Zhao et al., 2024b) in Figure 3.
Figure 3. Pathways of antibiotic-mercury interactions (Poulin et al., 2025).
Research indicates that the diversity and abundance of resistance genes in mercury-polluted environments exceed those in uncontaminated settings. The co-occurrence of antibiotic and mercury pollution is increasingly prominent in aquatic ecosystems—including rivers, lakes, wetlands, and aquaculture farms—primarily driven by synergistic effects from agricultural runoff, aquaculture wastewater, and industrial discharges. This leads to the dissemination of antibiotic resistance genes (ARGs) via mercury-induced horizontal gene transfer, amplifying risks associated with mercury methylation (Wen et al., 2022; Mahbub et al., 2020; Turel, 2002).
5.2 The relative contributions of chemical and biological factors to mercury transformation
In aquatic environments co-polluted by mercury and antibiotics, experimental evidence supports the relative importance of chemical complexation and microbial regulation in mercury methylation processes: Chemical complexation (e.g., tetracycline antibiotics forming complexes with Hg2+) indirectly promotes MeHg formation by enhancing Hg dissolution and release from sediments into the water phase, thereby increasing Hg bioavailability. However, its direct contribution is limited, primarily manifested in providing potential methyl donors during antibiotic degradation (Liang et al., 2018). In contrast, microbial regulation plays a more dominant role. In hypoxic aquatic environments, methylmercury production and degradation are primarily microbial processes. The transport of inorganic mercury from the extracellular environment of microorganisms and through outer and inner membranes are crucial steps leading to its biological methylation. The uptake of divalent inorganic mercury (II) is believed to be mediated by transport proteins, with Merc, MERP, and Mert playing significant roles (Barkay et al., 2003). Simultaneously, antibiotic exposure induces shifts in sulfate-reducing bacteria (SRB) and iron-reducing bacteria (IRB) community abundance, amplifying net MeHg production rates and elevating sediment MeHg/THg ratios. This effect is primarily driven by microbial-mediated enzymatic methylation rather than purely chemical pathways. Overall, chemical complexation primarily acts as a secondary mechanism regulating initial Hg availability, while microbial processes determine the main MeHg production and ecological risk amplification, particularly in anaerobic sediments (Heileen et al., 2013).
5.3 Key methodological differences
King et al. discovered through pure culture and marine sediment slurry experiments that methylmercury production varies significantly among phylogenetically distinct sulfate-reducing bacteria (SRBs) (Liang et al., 2018). The normalized mercury methylation rate (MMR) per cell for acetate-utilizing Desulfobacteriaceae family members (e.g., Desulfobacter, Desulfobacterium) was approximately three orders of magnitude higher than that of Desulfovibrionaceae family members (e.g., Desulfovibrio). Under sulfate-free conditions, the latter produced almost no methylmercury, indicating that their methylation is tightly coupled with sulfate respiration. Acetate-amended sediment slurry, dominated by Desulfobacteriaceae, exhibited significantly higher methylmercury production capacity when normalized by MMR/SRR, whereas lactate-amended and control groups showed no significant differences. Overall, mercury methylation capacity is closely associated with the genetic composition and carbon metabolism pathways of SRBs. Desulfobacteriaceae represent more efficient methylators in marine sediments, which is significant for understanding the control mechanisms of methylmercury formation and mercury pollution remediation. Liang et al. revealed key differences in antibiotic-mercury interactions through microcosm experiments: marine aquaculture sediments (MS) and reference sediments (RS) were divided into control and treatment groups, with Hg(NO3)2 (2 and 8 mg kg−1 dry weight) and tetracycline/oxytetracycline (TC/OTC, 2.5 g and 10 g kg−1 dry weight, respectively) added (K, E et al., 2000). Results showed decreased total sediment mercury (THg) concentrations during incubation (attributed to TC/OTC complexing Hg2+, releasing dissolved mercury), while methylmercury (MeHg) concentrations significantly increased (10%–40%) after 32 days, paralleling the decline in antibiotic concentrations. The authors proposed a mechanism: the high electronegativity of Hg2+ induces electron transfer from TC/OTC to Hg2+, reducing Hg2+ to Hg0, which subsequently reacts with CH3+ produced by antibiotic degradation to form MeHg. This study highlights that under high antibiotic concentrations, chemical complexation and degradation processes dominate the increased MeHg formation, differing from the microbial regulation-dominated mechanism at low concentrations. The differences primarily stem from experimental design and methodological sources, as shown in Figure 4.
6 Challenges in research and future directions
6.1 The diversity of relationships between antibiotic exposure and Hg migration and transformation
Antibiotics possess numerous functional groups, including carboxyl, hydroxyl, amino, and heterocyclic rings, along with electron-donating atoms, which can participate in synergistic, antagonistic, or addition-type complexation interactions with Hg. The complexation capacity is contingent upon the type of antibiotic and the characteristics of Hg. Antibiotics with higher concentrations of nitrogen, oxygen, and other electron-dense groups demonstrate enhanced Hg complexation. Nonetheless, an increase in functional groups may augment steric hindrance, hence diminishing complexation efficiency. Antibiotics with -CH3 groups facilitate Hg methylation in aquatic habitats by providing -CH3 to sediments during their degradation. Mercuric is converted to Hg0, which subsequently interacts with -CH3 groups from antibiotics to produce MeHg. Concurrently, -CH3 groups liberated during antibiotic degradation may interact with Hg0 to produce MeHg. Specific functional groups can boost both absorption capacity and selectivity due to their differing affinity for heavy metal ions.
6.2 Emerging pollutants requiring attention
Groundwater is an essential global water supply, increasingly threatened by pollution from human activities. Groundwater is typically less vulnerable to pollution by emerging contaminants than surface water; yet, various pollutants, including emerging contaminants, are still identified in groundwater. Karst aquifers exhibit heightened susceptibility to pollution relative to other lithologies, owing to direct infiltration via stream confluences, vertical shafts, and caverns. In addition to the four prevalent antibiotics and trace elements already noted, new contaminants include pesticides, personal care products, and microplastics, together with their metabolites and transformation products, remain present in environmental media, effects of antibiotics on Hg metabolism and bioaccumulation pathways in organisms as shown in Figure 5. Significant synergistic effects exist among these pollutants: Quinolone antibiotics promote bacterial mercury methylation, doubling methylmercury production (Kacper et al., 2024); mercury and other heavy metal contamination trigger increased abundance of ARGs in environmental microbiomes, accelerating horizontal gene transfer of antibiotic resistance (Balta et al., 2025); while microplastics significantly increase the bioavailability of antibiotics and heavy metals by 79%–138% (Evdokia and Nicolas, 2022). These pollutants can redistribute across environmental media and undergo global cycling through long-range transport. Their combined toxic effects from co-pollution far exceed those of individual pollutants, posing severe threats to ecosystems and human health. Their bioaccumulation in food webs, ecotoxicological impacts, and threats to local ecosystems and human health necessitate further thorough examination. This is especially crucial due to wetland’s significance for potable water resources and its function as a distinctive and fragile ecosystem.
7 Conclusion
7.1 Summary of existing studies
Research on environmental antibiotic residues has primarily focused on surface water, sediments, wastewater treatment plants, animal farms, and soil, with studies on wetland water bodies remaining relatively limited. The anaerobic environment and abundant carbon sources in wetland sediments support the growth of mercury-methylating microorganisms, promoting methylmercury formation. Understanding its production and degradation mechanisms is crucial for assessing human mercury exposure risks. Antibiotic molecules, rich in functional groups and electron-donating atoms, can engage in synergistic, antagonistic, or addition-type complexation reactions with mercury. Their methyl (-CH3) groups may also promote mercury methylation, with varying mercury capture capacities observed across different substitution sites. Key questions remain to be explored, including the mechanisms and influencing factors of mercury methylation, the role of antibiotics in mercury bioavailability, the mechanisms of mercury metabolism in organisms under antibiotic stress, and the patterns of mercury-antibiotic interactions. A comprehensive understanding of antibiotic-mercury interactions in wetland ecosystems requires integrating emerging analytical methods with interdisciplinary research frameworks. First, there is an urgent need to develop multi-pollutant transport and transformation models that couple hydrological dynamics, redox chemistry, and microbial activity to predict the spatiotemporal behavior of antibiotic-mercury complexes. Second, high-throughput genomics technologies offer new opportunities to reveal the colocalization and co-selection dynamics of antibiotic resistance genes (ARGs) and mercury resistance genes (MRGs) on mobile genetic elements. Third, mercury stable isotope geochemistry (δ202Hg, Δ199Hg) can effectively trace antibiotic-mediated mercury transformation pathways, with its fractionation characteristics distinguishing abiotic complexation from microbially driven methylation processes—yet its application remains underutilized. Finally, translating mechanistic findings into quantitative risk assessment frameworks is essential to evaluate synergistic or antagonistic effects of co-exposure, providing scientific basis for managing complexly polluted wetlands. Integrating these methodological advances with field studies in vulnerable wetland systems like wetlands represents a frontier for future research.
7.2 Outlook
Although this review has systematically summarized research progress on antibiotic-mercury interactions, wetland-specific biogeochemical processes warrant further investigation. Wetlands possess unique hydrological conditions, pronounced redox gradients, and abundant bioavailable organic carbon, collectively creating favorable environmental conditions for microbial mercury methylation. However, systematic understanding remains lacking regarding how these characteristics regulate antibiotic-mercury interactions. The following critical knowledge gaps require urgent attention: The impact of wetland redox fluctuations on the chelation kinetics between antibiotic functional groups (-COOH, -NH2, -CH3) and mercury speciation; The competitive or synergistic regulation of wetland-derived dissolved organic matter on mercury adsorption-desorption processes at specific structural sites of antibiotics (Maxime et al., 2021); Responses of wetland-specific microbial communities (particularly sulfate-reducing bacteria and methanogens) to antibiotic stress and their impact on methylmercury formation; Co-selection dynamics between mercury resistance genes and antibiotic resistance genes in anoxic wetland sediments (Yu et al., 2025). Given the scarcity of research on wetlands, future studies should integrate field investigations with controlled mesocosm experiments to elucidate wetland-specific mechanisms.
The co-selection of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) represents a critical yet understudied dimension in antibiotic-mercury interactions. The co-localization of ARGs and MRGs on mobile genetic elements (plasmids, transposons, and integrons) facilitates their horizontal transfer and environmental persistence (Gillieatt and Coleman, 2024). Three primary mechanisms currently proposed include: co-resistance (linked genes on the same genetic element), cross-resistance (a single gene conferring resistance to both stressors), and co-regulation (shared regulatory pathways). However, the molecular mechanisms underlying these phenomena remain poorly defined, and quantitative studies quantifying how specific metal types, bacterial taxa, and environmental conditions regulate co-selection dynamics are scarce. Existing evidence primarily stems from pure cultures or conventional aquatic systems via metagenomic studies. Yet wetland-specific factors—such as redox fluctuations, DOM-metal complexation, and unique microbial communities—may significantly influence the coevolutionary trajectories of ARGs and MRGs, necessitating validation through integrated research approaches.
From an environmental management perspective, natural wetlands serve as hotspots for mercury methylation. Their anaerobic sedimentary environments and abundant organic matter provide ideal methylation conditions for microorganisms such as sulfate-reducing bacteria. When these areas simultaneously receive wastewater discharges containing antibiotics or agricultural runoff, the combined pollution effects of mercury and antibiotics become particularly pronounced. The synergistic interaction between these two pollutants primarily manifests through co-selection mechanisms: Persistent mercury exposure selects microbial populations carrying mercury resistance operons. These resistance genes are often colocalized with antibiotic resistance genes (e.g., sulfonamides, aminoglycosides, tetracyclines) on the same plasmid. Consequently, antibiotic resistance can be indirectly maintained and transmitted via mercury pollution even in the absence of direct antibiotic selection pressure. Therefore, wastewater treatment facilities should minimize mercury and antibiotic loads before discharge into natural wetlands. Controlling agricultural nonpoint source pollution is equally critical, as improper disposal of livestock manure and antibiotic-containing feed additives can turn farmlands into sources transporting pollutants to surrounding wetlands. Monitoring systems should be designed to assess multiple media including water bodies, sediments, and biological tissues. Beyond conventional indicators like total mercury and methylmercury, evaluations must incorporate antibiotic residue concentrations, relative abundance of typical resistance genes, and co-occurrence patterns of mercury resistance genes with antibiotic resistance genes. This approach provides scientific basis for assessing composite pollution risks in natural wetlands and formulating conservation strategies.
Author contributions
KD: Methodology, Writing – original draft, Project administration, Data curation, Conceptualization, Funding acquisition. JY: Validation, Writing – original draft. CD: Writing – original draft, Resources, Visualization. CG: Investigation, Writing – original draft. CL: Writing – original draft, Software. FH: Formal Analysis, Writing – original draft. DW: Funding acquisition, Writing – original draft. YY: Writing – review and editing, Supervision, Validation.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This research was funded by the Guangxi Natural Science Foundation (grant number 2025GXNSFDA069043 and 2025GXNSFBA069116), the Guangxi Key Research and Development Program (grant number GuikeAB24010118), the Natural Science Foundation of China (grant number 52260023) and the Research funds of The Guangxi Key Laboratory of Theory and Technology for Environmental Pollution Control (grant number 2301Z003).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Keywords: compound pollution, ecological risk, Mercury (Hg), methylation, migration, transformation
Citation: Dong K, Yang J, Du C, Ge C, Liao C, Hui F, Wang D and Yao Y (2026) The role of antibiotic-mercury interactions in wetlands: a review of methylation processes and ecological implications. Front. Environ. Sci. 13:1720362. doi: 10.3389/fenvs.2025.1720362
Received: 07 October 2025; Accepted: 15 December 2025;
Published: 09 January 2026.
Edited by:
Changjin Ou, Nantong University, ChinaReviewed by:
Rute Isabel Cesário, University of Lisbon, PortugalYanbin Li, Ocean University of China, China
Copyright © 2026 Dong, Yang, Du, Ge, Liao, Hui, Wang and Yao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yi Yao, MjAwODAxOEBnbHV0LmVkdS5jbg==
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