Regular time-dependent cross-phenomena induced by hormesis: A case study of binary antibacterial mixtures to Aliivibrio fischeri.

Time-dependent cross-phenomenon in which the cross between the actual concentration-response curve (CRC) for mixture crosses the CRCs for reference model varies with time has been frequently reported in previous studies, expressed as a heterogeneous pattern of joint toxic action. However, the variation tendency of time-dependent cross-phenomenon is rarely addressed. In this study, the joint toxic actions of binary antibacterial mixtures (i.e., two quorum sensing inhibitors, tetracycline hydrochloride, erythromycin, and chloramphenicol with sulfonamides) were judged using independent action (IA) model to find the variation tendency of time-dependent cross-phenomenon. The results show that the time-dependent cross-phenomena of the test binary antibacterial mixtures follow a unified variation tendency and the corresponding joint toxic actions change regularly with an increase of both concentration and time. Through investigating the relationship between the stimulatory and inhibitory modes of action for the single agents and the time-dependent cross-phenomena of binary mixtures, the regular time-dependent cross-phenomena is speculated to be derived from the hormetic effects of the components in the mixtures. This study offers an advance for the variation tendency and mechanistic explanation of time-dependent cross-phenomenon, which will provide a support for the future development in the exploration of time-dependent cross-phenomenon and environmental risk assessment of pollutant mixtures.

Hormetic dose-dependent response about typical antibiotics and their mixtures on plasmid conjugative transfer of Escherichia coli and its relationship with toxic effects on growth.

Bacterial resistance caused by the abuse of antibiotics has attracted worldwide attention. However, there are few studies exploring bacterial resistance under the environmental exposure condition of antibiotics that is featured by low-dose and mixture. In this study, sulfonamides (SAs), sulfonamide potentiators (SAPs) and tetracyclines (TCs) were used to determine the effects of antibiotics on plasmid RP4 conjugative transfer of Escherichia coli (E. coli) under single or combined exposure, and the relationship between the effects of antibiotics on conjugative transfer and growth was investigated. The results show that the effects of single or binary antibiotics on plasmid RP4 conjugative transfer all exhibit a hormetic phenomenon. The linear regression reveals that the concentrations of the three antibiotics promoting conjugative transfer are correlated with the concentrations promoting growth and the physicochemical properties of the compounds. The combined effects of SAs-SAPs and SAs-TCs on plasmid conjugative transfer are mainly synergistic and antagonistic. While SAPs provide more effective concentrations for the promotion of conjugative transfer in SAs-SAPs mixtures, SAs play a more important role in promoting conjugative transfer in SAs-TCs mixtures. Mechanism explanation shows that SAs, SAPs and TCs inhibit bacterial growth by acting on their target proteins DHPS, DHFR and 30S ribosomal subunit, respectively. This study indicates that toxic stress stimulates the occurrence of conjugative transfer and promotes the development of bacterial resistance, which will provide a reference for resistance risk assessment of antibiotic exposure.

QSAR-based investigation on antibiotics facilitating emergence and dissemination of antibiotic resistance genes: A case study of sulfonamides against mutation and conjugative transfer in Escherichia coli.

Antibiotic resistance genes (ARGs), which are emerging environmental contaminants, have posed great threats to global public health. Although extensive efforts have been undertaken to investigate ARG pollution, little attention has been paid to the structural information of antibiotics when exploring their impact on the emergence and dissemination of ARGs. In this study, setting Escherichia coli (E. coli) as the test organism, the effects of sulfonamides (SAs) on growth, mutation frequency and conjugative transfer frequency were tested, and quantitative structure-activity relationship (QSAR) was used to quantitatively analyze the promotion of SAs on these biological effects and explore their possible mechanism. The constructed QSAR models reveal that SAs may increase expression of the FtsZ protein and pili in E. coli via binding to the SdiA protein, ultimately leading to SAs facilitation of growth, mutation frequency and conjugative transfer frequency. The results indicate that SAs can produce selective pressure on E. coli to promote the emergence and dissemination of ARGs. This study provides reference data for further investigation of the emergence and dissemination of ARGs under antibiotic exposure and a new perspective for the mechanistic exploration of ARG pollution.

Combination of sulfonamides, silver antimicrobial agents and quorum sensing inhibitors as a preferred approach for improving antimicrobial efficacy against Bacillus subtilis.

More and more antibacterial agents are used together to treat bacterial infections in diverse fields, but the overuse of antibacterial agents may cause the environmental pollution of antibiotic resistance genes (ARGs). In order to reduce the use of antimicrobial agents, the potential joint effects of quorum-sensing inhibitors (QSIs) and traditional antimicrobial agents have been proposed to be effective. In this study, the joint effects of traditional antimicrobial agents, represented by sulfonamides (SAs) and silver antibacterial agents (silver nitrate (AgNO3) and nanosilver (AgNP, 5 nm)), and five potential QSIs, were investigated using B. subtilis. It was found that AgNP showed higher toxicity than AgNO3, whereas the joint effects on B. subtilis showed no difference between AgNO3 and AgNP when they combined with SAs or QSIs, respectively. In general, AgNO3 and AgNP presented synergetic and additive effects with QSIs, but additive and antagonistic effects with SAs; SAs exhibited synergetic, additive and antagonistic effects with different QSIs whether in binary or ternary mixed system. Moreover, it was found that the use of antimicrobials was reduced and the synergistic combined toxicity of antimicrobial agents on B. subtilis was increased through the addition of the QSIs. This study can offer a valuable reference for the combined medication of the different antimicrobial agents, which will benefit the environmental and human health.

A comparative study on the binary and ternary mixture toxicity of antibiotics towards three bacteria based on QSAR investigation.

Antibiotics have become common pollutants in the environment. In most cases, the antibiotics in the environment exist as mixtures, posing joint effects on the organisms. Therefore, the mixture toxicity of the antibiotics can better reflect their environmental risks. In this paper, three types of commonly used antibiotics, i.e., sulfonamides (SAs), SA potentiators (SAPs) and tetracyclines (TCs) were investigated for their binary and tertiary mixture toxicity on three bacteria, Escherichia coli (E. coli), Vibrio fischeri (V. fischeri) and Bacillus subtilis (B.subtilis). It was found that SA-SAP mixtures and SA-SAP-TC mixtures presented synergetic effects on the three bacteria, while SA-TC and SAP-TC mixtures showed antagonistic effects. QSAR investigation suggested that the actual concentration ratio of the components in a mixture could vary a lot from the designed concentration ratio; moreover, the TCs in the ternary mixtures altered the toxic ratio of SAs and SAPs, which lead to the varying joint effects of the ternary mixtures on different bacteria. The present research proposes a novel idea for the mechanistic study of the mixture toxicity, both theoretically and methodologically; and the QSAR studies provide a reference for the prediction of the mixture toxicity, which could be helpful to the risk assessment on joint exposure to antibiotic mixtures.

A study on the role that quorum sensing play in antibiotic-resistant plasmid conjugative transfer in Escherichia coli.

Horizontal genes transfer (HGT) plays an important role in the dissemination of antibiotic resistance genes (ARGs) in the environment. However, the mechanisms of HGT of ARGs under the influence of antibiotics in sub-MIC remain rarely explored. Moreover, given its collective nature, HGT was considered to be relative to quorum sensing (QS) system. To investigate whether QS has any impact on horizontal gene transfer of ARGs, experiments were conducted to determine the conjugative efficiency of plasmid RP4 on Escherichia coli (E.coli) under the influences of tetracyclines (TCs), quorum sensing autoinducers (AIs) and quorum sensing inhibitors (QSIs). The results indicated that the sub-MIC TCs could facilitate the conjugative transfer of RP4, a process which could be enhanced by AIs but inhibited by QSIs. This study demonstrated the roles that QS played in the dissemination of ARGs, and provided theoretical insights into the mechanism of HGT of ARGs in the environment.

Similarities and differences in combined toxicity of sulfonamides and other antibiotics towards bacteria for environmental risk assessment.

Antibiotics as a type of environmental contaminants are typically exposed to chemical mixtures over long periods of time, so chronic combined toxicity is the best way to perform an environmental risk assessment. In this paper, the individual and combined toxicity of sulfonamides (SAs), sulfonamide potentiators (SAPs), and doxycycline hyclate (DH) were tested on gram-positive (Bacillus subtilis, B. subtilis) and gram-negative (Escherichia coli, E. coli) bacteria. The individual toxicity of antibiotics on the two bacteria could be ranked in the same order: SAs < SAPs < DH. But E. coli was more sensitive than B. subtilis to the antibiotics, which was likely due to both the different abilities of antibiotics to pass through the cell membrane and the varied capacities to bind target proteins between the two bacteria. In addition, the binary mixtures of SAs-SAPs, SAs-DH, and SAs-SAs exhibited synergistic, antagonistic, and additive effects on both of the bacteria but in different magnitudes as represented by the toxicity units (TU). And we found the different TU values were result from the different effective concentrations of antibiotic mixtures based on the approach of molecular docking and quantitative structure-activity relationships (QSARs). Moreover, from the results of risk assessment, it should be noted that the mixture of SAs and other antibiotics may pose a potential environmental risk assessment due to their combined action with the current environmentally realistic concentrations.

Mechanism-based QSAR Models for the Toxicity of Quorum Sensing Inhibitors to Gram-negative and Gram-positive Bacteria.

Quorum sensing inhibitors (QSIs) are a promising alternative to the antibiotics and unlikely to induce drug resistance. However, toxicity studies on the QSIs remain limited; therefore in this paper we investigated the acute (15 min) and chronic (24 h) toxicity of some potential QSIs on both gram-negative (V. fischeri) and gram-positive bacteria (B. subtilis). It was found that the toxicity of the QSIs differed with the toxicity test periods. QSAR models were developed for both the acute and chronic toxicity, using the interaction energies between QSIs and the relevant proteins, and the frontier orbital energies. Based on the QSAR models, it was suggested that QSIs primarily bind with the luciferase at 15 min, but LuxR at 24 h in V. fischeri; whereas in B. subtilis, the QSIs mainly bind with LuxS. Our study provided an insight into the toxicity mechanism for QSIs during different exposure periods.

The underlying toxicological mechanism of chemical mixtures: a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum.

Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction.

Efficient oxidative debromination of decabromodiphenyl ether by TiO2-mediated photocatalysis in aqueous environment.

Direct evidence was first demonstrated for the oxidative degradation of decabromodiphenyl ether (BDE209) in aqueous TiO(2) dispersions under UV irradiation (λ > 340 nm). BDE209 was hardly debrominated over TiO(2) in UV-irradiated acetonitrile dispersions, but the addition of water into the dispersions greatly enhanced its photocatalytic oxidative debromination. The debromination efficiency of BDE209 as high as 95.6% was achieved in aqueous TiO(2) dispersions after 12 h of UV irradiation. The photocatalytic oxidation of BDE209 resulted in generation of aromatic ring-opening intermediates such as brominated dienoic acids, which were further degraded by prolonging UV irradiation time. The photocatalytic oxidative debromination of BDE209 was further confirmed by the observation that the BDE209 degradation in water-acetonitrile mixtures with different water contents was positively correlated with the formation of •OH radicals, but not photogenerated electrons. The use of water not only avoided the scavenging of reactive radicals by organic solvent but also enhanced the adsorption of BDE209 on the surface of TiO(2), both of which favor the contact of BDE209 with photogenerated holes and •OH species. The confirmation of efficient oxidative degradation and debromination of BDE209 is very important for finding new ways to remove polybrominated diphenyl ethers from the environment.

A docking-based receptor library of antibiotics and its novel application in predicting chronic mixture toxicity for environmental risk assessment.

As organisms are typically exposed to chemical mixtures over long periods of time, chronic mixture toxicity is the best way to perform an environmental risk assessment (ERA). However, it is difficult to obtain the chronic mixture toxicity data due to the high expense and the complexity of the data acquisition method. Therefore, an approach was proposed in this study to predict chronic mixture toxicity. The acute (15 min exposure) and chronic (24 h exposure) toxicity of eight antibiotics and trimethoprim to Vibrio fischeri were determined in both single and binary mixtures. The results indicated that the risk quotients (RQs) of antibiotics should be based on the chronic mixture toxicity. To predict the chronic mixture toxicity, a docking-based receptor library of antibiotics and the receptor-library-based quantitative structure-activity relationship (QSAR) model were developed. Application of the developed QSAR model to the ERA of antibiotic mixtures demonstrated that there was a close affinity between RQs based on the observed chronic toxicity and the corresponding RQs based on the predicted data. The average coefficients of variations were 46.26 and 34.93 % and the determination coefficients (R (2)) were 0.999 and 0.998 for the low concentration group and the high concentration group, respectively. This result convinced us that the receptor library would be a promising tool for predicting the chronic mixture toxicity of antibiotics and that it can be further applied in ERA.

Model of hormesis and its toxicity mechanism based on quorum sensing: a case study on the toxicity of sulfonamides to Photobacterium phosphoreum.

During the past two decades, the phenomenon of hormesis has gained increasing recognition in environmental and toxicological communities. However, the mechanistic understanding of hormesis, to date, is extremely limited. Herein is proposed a novel parametric model with a mechanistic basis and two model-based parameters for hormesis that was successfully applied to the hormetic dose-response observed in the chronic toxicity of sulfonamides on Photobacterium phosphoreum. On the basis of the methods of molecular docking and quantitative structure-activity relationships (QSARs), we proposed a mechanistic hypothesis for hormesis that introduces for the first time the concept of quorum sensing in toxicological studies and explains the mechanism at the level of the receptors. The mechanistic hypothesis stated that (1) specific target binding like interaction with LuxR may contribute to transcriptional activation leading to enhanced luciferase activity at low dose exposure of sulfonamides, and (2) as the dose of sulfonamides increases, more sulfonamides competitively bind to dihydropteroate synthase, which inhibit the biosynthesis of folic acid and thus provoke toxicity. This mechanistic hypothesis, which explains both the dose-dependent and time-dependent features of hormesis, could give new insight into the mechanistic study of hormesis.

Application of the similarity parameter (λ) to prediction of the joint effects of nonequitoxic mixtures.

Although environmental contaminants are usually encountered as nonequitoxic mixtures, most studies have investigated the toxicity of equitoxic mixtures. In the present study, a method for prediction of the toxicity of nonequitoxic mixtures was developed using the similarity parameter (λ). The joint effect of multiple contaminants at the median inhibition concentration in equitoxic ([Formula: see text]) and nonequitoxic ([Formula: see text]) binary, ternary, and quaternary mixtures was investigated using Vibrio fischeri. The observed results indicate that the concentration ratios of individual chemicals in the mixtures influenced the joint effects, and that λ could be employed to evaluate the relation between [Formula: see text] and [Formula: see text]. Prediction models for the joint effects of nonequitoxic ([Formula: see text]) mixtures were derived from a combination of [Formula: see text] and λ. The predictive capabilities of these models were validated by comparing the predicted data with the observed data for binary, ternary, and quaternary mixtures. The prediction models have promising applications in controlling environmental pollution, evaluating drug interactions, and optimizing combinations of pesticides used in agriculture.

Screening and prioritizing substances in groundwater in the Beijing-Tianjin-Hebei region of the North China Plain based on exposure and hazard assessments.

Screening and prioritizing hazardous substances in groundwater is crucial to monitor and control groundwater quality. Total of 283 substances were determined in 213 groundwater samples from the Beijing-Tianjin-Hebei region during 2019-2020. 184 substances were screened as candidates. 22 prioritizing indicators were evaluated and scored for the candidates to reflect their occurrence, mobility, persistence, bioaccumulation, acute and chronic ecotoxicities with different trophic levels, and long-term human health effects. Multi-attribute decision-making technologies were applied to prioritize these candidates, including analytic hierarchy process (AHP), TOPSIS and VIKOR. Greater weightings in AHP were assigned to attributes of occurrence and acute toxicity by experts' judgment. Hierarchical cluster analysis and principal component analysis were used to transform initial matrix with the 22 indicators into an orthogonalized matrix with 6 principal components, which represented general toxicity to aquatic organism and mammal, bioaccumulation, carcinogenicity & mutagenicity, persistence, and teratogenicity & endocrine, respectively. VIKOR and TOPSIS results were similar, but different from the AHP ranking. Two filter criteria harmonized their difference. Twenty-three substances were proposed as the priority substance with high hazard and potential exposure, and nitrate-nitrogen and ammonia-nitrogen were selected as additional priority substance frequently and extensively exceeding official groundwater quality standard on the regional scale.

A K(ow)-based QSAR model for predicting toxicity of halogenated benzenes to all algae regardless of species.

In this study, a total of 40 tests of the toxicity of 8 halogenated benzenes to five algal species were performed. The result demonstrated that the toxicity of halogenated benzenes to five algal species was directly related to the hydrophobicity of the chemicals and the lipid content of the algae. Based on the results, we developed a K(ow)-based quantitative structure-activity relationship (QSAR) model: log(1/EC50) = 1.050 logK(ow) + 1.429 log(1/lipid)-3.224 with n = 40, r² = 0.946, S.E. = 0.211, F = 323.933 at p < 0.001. This model provides evidence that the toxicity of halogenated benzenes to these five algae tested is related to the slower transference into lipid. This model can potentially be generalized to other algal species and toxicants.

Spatial variation, water quality, and health risk assessment of trace elements in groundwater in Beijing and Shijiazhuang, North China Plain.

Metal(loid)s pollution of groundwater in northern China is of great concern due to the increasing shortage of fresh water resources. In the present study, total 159 of groundwater samples were collected from the Miyun-Huairou-Shunyi (MHS) districts in Beijing city and the Hutuo River Plain (HRP) in Shijiazhuang city. Nineteen trace elements dissolved in groundwater were measured. Results showed that Al (12.3 %), Mn (5.3%), Zn (1.8%), As (1.8%), and Pb (1.8%) in the MHS samples, and Mn (2.2%) in the HRP samples exceeded their standard threshold of WHO and China. Exceedance of trace elements was attributed to both geochemical background and local human activities. Human health risk assessment showed that local consumers were exposed at a low level of health risk, except in specific area with a high level of arsenic. Elements of arsenic and chromium were important risk contributors in the two regions. The risk of oral exposure was greater than that of skin uptake. Children were more susceptible to non-carcinogenic risk and less to carcinogenic risk than adults. A Nemerow index and CRITIC-weighted WQI were applied to classify groundwater quality. The results from the two methods were comparable to a large extend. More population living in plain rather than mountain resulted in a gradual deterioration trend of groundwater quality from mountain to plain. The samples with poor water quality were almost collected in the area with heavy industrial and agricultural activities. The CRITIC-weighted WQI was recommended for groundwater quality assessment. A simple classification criterion was reformulated based on the MHS hazard index analysis. The groundwaters in the two research fields were not seriously polluted, but potential risks should not be ignored.

Hormetic dose-responses for silver antibacterial compounds, quorum sensing inhibitors, and their binary mixtures on bacterial resistance of Escherichia coli.

Silver antibacterial compounds (SACs) and quorum sensing inhibitors (QSIs), as the potential antibiotic substitutes, have been recommended to prevent and treat microbial infections for the purpose of controlling the increasingly serious bacterial resistance induced by the abuse of antibiotics. However, there is little information regarding the resistance risk of these compounds, especially their mixtures. In this study, bacterial mutation and RP4 plasmid conjugative transfer among bacteria were used to characterize the bacterial endogenous and exogenous resistance, respectively. The effects of SACs (including silver nitrate (AgNO3) and silver nanoparticle (AgNP)), QSIs, and their binary mixtures on the bacterial resistance were investigated via setting the frequency of mutation and conjugative transfer in Escherichia coli (E. coli) as the test endpoints. The results indicated that these two endpoints exhibited hormetic dose-responses to each treatment. Furthermore, the joint resistance actions between SACs and QSIs were all judged to be antagonism. Correlation analysis suggested that the promotion of the bacterial resistance in each treatment was closely related to its toxicity. It was speculated that AgNO3 and AgNP might both release Ag+ ions to facilitate the E. coli resistance, while QSIs probably acted on LsrR and SdiA proteins to stimulate the bacterial mutation and accelerate the RP4 plasmid conjugative transfer, respectively. These findings imply that the bacteria may generate targeted stress response to the survival pressure from environmental compounds, displaying hormetic phenomenon in resistance-related test endpoints. This study provides a new insight into the resistance risk induced by SACs and QSIs, benefiting the environmental risk assessment of these compounds from the perspective of bacterial resistance.

Investigations on the influence of energy source on time-dependent hormesis: A case study of sulfadoxine to Aliivibrio fischeri in different cultivation systems.

Hormesis is a biphasic dose-response relationship featured by low-dose stimulation and high-dose inhibition. Although the hormetic phenomenon has been extensively studied over the past decades, there is little information regarding the influence of energy source on the occurrence of hormesis, especially the time-dependent one. In this study, to explore the role of cultivation system's energy source in time-dependent hormesis, the toxic dose-responses of Aliivibrio fischeri (A. fischeri) bioluminescence to Sulfadoxine (SDX) during 24 h were determined in four cultivation systems with different energy source conditions. The results indicated that the time-dependent hormetic effects were induced by SDX in all cultivation systems: SDX triggered hormetic phenomenon on the bioluminescence at each growth stage over 24 h in the cultivation systems with sufficient and insufficient energy source; due to the diauxic growth of A. fischeri under multiple energy source conditions, the hormetic effects of SDX gradually disappeared after the preferred energy source was used up. It was speculated that the inhibitory action of SDX was derived from its interaction with DHPS to impede the synthesis of proteins, and SDX bound with AC to upregulate the quorum sensing (QS) system to exhibit the stimulatory action. Comparing the time-dependent hormesis in each cultivation system, it was obtained that the energy source could impact the hourly maximum stimulatory rate, the EC50 of SDX, and the time point that hormesis occurred, which might result from the influence of energy source on the stimulatory and inhibitory actions of SDX through regulating the metabolic system (individual level) and QS system (group level) of bacteria. This study clarifies the importance of energy source for hormesis occurrence, which may further promote the development of hormesis.

In-situ and ex-situ measurement of hydrophobic organic contaminants in soil air based on passive sampling: PAH exchange kinetics, non-equilibrium correction and comparison with traditional estimations.

It is a great challenge to accurately estimate chemical activity of hydrophobic organic contaminants in field soils. Ex-situ and in-situ determinations were developed for this purpose based on low-density polyethylene (LDPE) passive sampling and non-equilibrium correction by release of performance reference compounds (PRCs) previously spiked to the samplers. This work investigated kinetic processes of target contaminants' uptake into and PRCs' release from the sampler in an ex-situ soil suspension incubated for 100 days. A close agreement of kinetic parameters for pyrene's (target) uptake into and deuterated pyrene's (PRC) release from LDPE indicated their similar exchange kinetics. Three kinetic models were developed to correct uptake of target compounds in non-equilibrium conditions via release processes of PRCs. The second-order kinetic model was recommended for ex-situ measurements. The PRC-based non-equilibrium corrections were further applied to in-situ static passive sampling from several weeks to months in a PAH-contaminated field site. Two-weeks' deployments were sufficient for quantifying lighter PAHs (logKOA < 8.0), but not recommended to accurately estimate heavier PAHs (logKOA > 9.0), even if over four months. Concentration estimates from the in-situ and ex-situ passive samplings were comparable in order of magnitude with traditional estimation from equilibrium partitioning models considering both organic and black carbon fractions.

Resistance risk induced by quorum sensing inhibitors and their combined use with antibiotics: Mechanism and its relationship with toxicity.

The abuse of antibiotics has brought out serious bacterial resistance, which threatens the ecological environment and human health. Quorum sensing inhibitors (QSIs), as a new kind of potential antibiotic substitutes that are theoretically difficult to trigger bacterial resistance, are recommended to individually use or jointly use with traditional antibiotics. However, there are few studies on the resistance risk in the use of QSIs. In this study, the influence of QSIs alone or in combination with sulfonamides (SAs) on conjugative transfer and mutation of Escherichia coli (E. coli) was investigated to explore whether QSIs have the potential to induce bacterial resistance. The results show that QSIs may facilitate plasmid RP4 conjugative transfer by binding with SdiA protein to regulate pilus expression, and interact with LsrR protein to increase SOS gene expression, inducing gene mutation. The QSIs-SAs mixtures could promote plasmid RP4 conjugative transfer and mutation in E. coli, and the main joint effects are synergism and antagonism. Furthermore, there is a good correlation among conjugative transfer, mutation, and growth inhibition of QSIs-SAs to E. coli. It could be speculated that bacteria may delay cell division to provide sufficient energy and time for regulating conjugative transfer and mutation under the stress of QSIs and their combined exposure with antibiotics, which is essentially a balance between bacterial resistance and toxicity. This study provides a reference for the resistance risk assessment of QSIs and benefits the clinical application of QSIs.