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861400.9979Polystyrene nanoparticles induce biofilm formation in Pseudomonas aeruginosa. In recent years, micro/nanoplastics have garnered widespread attention due to their ecological risks. In this study, we investigated the effects of polystyrene nanoparticles (PS-NPs) of different sizes on the growth and biofilm formation of Pseudomonas aeruginosa PAO1. The results demonstrated that exposure to certain concentrations of PS-NPs significantly promoted bacterial biofilm formation. Meanwhile, we comprehensively revealed its mechanism whereby PS-NPs induced oxidative stress and altered bacterial membrane permeability by contacting or penetrating bacterial membranes. To counteract the stimulation by PS-NPs and reduce their toxicity, bacteria enhanced biofilm formation by upregulating the expression of biofilm-related genes, increasing EPS and virulence factors secretion, and enhancing bacterial motility through the participation of the quorum sensing (QS) system. Additionally, we also found that exposure to PS-NPs enhanced bacterial antibiotic resistance, posing a challenge to antimicrobial therapy. Our study reveals the toxic effects of nanoplastics and the defense mechanisms of bacteria, which has important implications for the risk assessment and management of environmental nanoplastics.202438442601
851310.9976Chlorine disinfection facilitates natural transformation through ROS-mediated oxidative stress. The bacterial infection that involves antimicrobial resistance is a rising global threat to public health. Chlorine-based water disinfection processes can inactivate antibiotic resistant bacteria. However, at the same time, these processes may cause the release of antibiotic resistance genes into the water as free DNA, and consequently increase the risk to disseminate antibiotic resistance via natural transformation. Presently, little is known about the contribution of residual chlorine affecting the transformation of extracellular antibiotic resistance genes (ARGs). This study investigates whether chloramine and free chlorine promote the transformation of ARGs and how this may occur. We reveal that both chloramine and free chlorine, at practically relevant concentrations, significantly stimulated the transformation of plasmid-encoded ARGs by the recipient Acinetobacter baylyi ADP1, by up to a 10-fold increase. The underlying mechanisms underpinning the increased transformations were revealed. Disinfectant exposure induced a series of cell responses, including increased levels of reactive oxygen species (ROS), bacterial membrane damage, ROS-mediated DNA damage, and increased stress response. These effects thus culminated in the enhanced transformation of ARGs. This promoted transformation was observed when exposing disinfectant-pretreated A. baylyi to free plasmid. In contrast, after pretreating free plasmid with disinfectants, the transformation of ARGs decreased due to the damage of plasmid integrity. These findings provide important insight on the roles of disinfectants affecting the horizontal transfer of ARGs, which could be crucial in the management of antibiotic resistance in our water systems.202133941886
859820.9976Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer. Antimicrobial resistance (AMR) poses a worldwide threat to human health and biosecurity. The spread of antibiotic resistance genes (ARGs) via conjugative plasmid transfer is a major contributor to the evolution of this resistance. Although permitted as safe food additives, compounds such as saccharine, sucralose, aspartame, and acesulfame potassium that are commonly used as nonnutritive sweeteners have recently been associated with shifts in the gut microbiota similar to those caused by antibiotics. As antibiotics can promote the spread of antibiotic resistance genes (ARGs), we hypothesize that these nonnutritive sweeteners could have a similar effect. Here, we demonstrate for the first time that saccharine, sucralose, aspartame, and acesulfame potassium could promote plasmid-mediated conjugative transfer in three established conjugation models between the same and different phylogenetic strains. The real-time dynamic conjugation process was visualized at the single-cell level. Bacteria exposed to the tested compounds exhibited increased reactive oxygen species (ROS) production, the SOS response, and gene transfer. In addition, cell membrane permeability increased in both parental bacteria under exposure to the tested compounds. The expression of genes involved in ROS detoxification, the SOS response, and cell membrane permeability was significantly upregulated under sweetener treatment. In conclusion, exposure to nonnutritive sweeteners enhances conjugation in bacteria. Our findings provide insight into AMR spread and indicate the potential risk associated with the presence of nonnutritive sweeteners.202133589766
859930.9976Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation. Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyi ADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilis and mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects.202234465899
852640.9975Size-dependent enhancement on conjugative transfer of antibiotic resistance genes by micro/nanoplastics. Recently micro/nanoplastics (MNPs) have raised intensive concerns due to their possible enhancement effect on the dissemination of antibiotic genes. Unfortunately, data is still lacking to verify the effect. In the study, the influence of polystyrene MNPs on the conjugative gene transfer was studied by using E. coli DH5ɑ with RP4 plasmid as the donor bacteria and E. coli K12 MG1655 as the recipient bacteria. We found that influence of MNPs on gene transfer was size-dependent. Small MNPs (10 nm in radius) caused an increase and then a decrease in gene transfer efficiency with their concentration increasing. Moderate-sized MNPs (50 nm in radius) caused an increase in gene transfer efficiency. Large MNPs (500 nm in radius) had almost no influence on gene transfer. The gene transfer could be further enhanced by optimizing mating time and mating ratio. Scavenging reactive oxygen species (ROS) production did not affect the cell membrane permeability, indicating that the increase in cell membrane permeability was not related to ROS production. The mechanism of the enhanced gene transfer efficiency was attributed to a combined effect of the increased ROS production and the increased cell membrane permeability, which ultimately regulated the expression of corresponding genes.202235278945
848950.9975Signaling molecules accelerate the transmission of antibiotic resistance genes under the stress of copper. Heavy metals can accelerate the dissemination of antibiotic resistance genes (ARGs) in aquatic environments by imposing environmental stresses. Signaling molecules play a role in bacterial communication and help bacteria adapt to environmental stresses. However, little is known whether the presence of signaling molecules has an effect on the spread of ARGs induced by heavy metals. In this study, we investigated how N-decanoyl-L-homoserine lactone (C10-HSL) affects copper-induced conjugative transfer of ARGs. We calculated the conjugative transfer frequency and measured reactive oxygen species (ROS) production, membrane permeability, and the expression of relevant genes. The results demonstrated that the addition of C10-HSL increased the conjugative transfer frequency of ARGs under copper ions (Cu(2+)) stress, showing a 7.2-fold increase under 0.5 μM Cu(2+) and 0.39 μM C10-HSL treatment compared to the control. This enhancement was associated with elevated intracellular ROS production and increased membrane permeability. The reduced conjugative transfer frequency under anaerobic conditions or with thiourea treatment supported the key role of ROS in this process. Furthermore, ROS overproduction triggered the SOS response, as evidenced by a 9-fold upregulation of recA expression. C10-HSL also modulated membrane-associated gene expression by upregulating outer membrane porins and downregulating efflux pump genes under Cu(2+)stress. This study provides a new insight into the spread of ARGs in aquatic environments.202540840413
848860.9975Antihistamine drug loratadine at environmentally relevant concentrations promotes conjugative transfer of antibiotic resistance genes: Coeffect of oxidative stress and ion transport. Due to the widespread use of loratadine (LOR) as an antihistamine, it is widely distributed in the environment as an emerging contaminant. However, its impact on the dissemination of antibiotic resistance genes (ARGs) remains unclear. This study investigated the effect of LOR on the conjugative transfer of ARGs and elucidated the potential mechanisms through transcriptome analysis. The results showed that LOR significantly promoted the frequency of conjugative transfer up to 1.5- to 8.6-fold higher compared with the control group. Exposure to LOR increased reactive oxidative species (ROS) and intracellular Ca(2+) concentrations, leading to the upregulation of expression of genes related to transmembrane transport and SOS response. Meanwhile, it stimulated the increase of cell membrane permeability. Moreover, LOR exposure could enhance H(+) efflux in donor bacteria, resulting in the decrease of intracellular pH and the elevation of transmembrane potential, which could induce the increase of ion transport, thereby promoting plasmid efflux from the cell membrane. Based on this, we inferred that LOR can induce an increase in ROS level and intracellular Ca(2+) concentrations, and promoted the efflux of intracellular H(+). This, in turn, triggered the intensification of various ion transport processes on the cell membrane, thereby increasing membrane permeability and accelerating plasmid efflux. Ultimately, the coeffect of oxidative stress response and ion transport promoted conjugative transfer. This study demonstrated that LOR significantly promotes plasmid-mediated conjugative transfer of ARGs, providing novel insights into the mechanisms underlying this process.202539919578
859770.9975Non-caloric artificial sweeteners exhibit antimicrobial activity against bacteria and promote bacterial evolution of antibiotic tolerance. Non-caloric artificial sweeteners are being widely used as safe table sugar substitutes with highly intensive sweetness but low calories. Previous studies have suggested that some of the sweeteners can alter the gut microbiota composition and promote horizontal transfer of antibiotic resistance genes across bacterial genera. However, little is known about whether these sweeteners could show antibiotic-like antimicrobial activity against bacteria, especially gut relevant bacteria. Whether they could affect evolutional trajectory of antibiotic resistance or tolerance in bacteria is also not clear yet. Here we investigated four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) against both Gram-negative (Escherichia coli and Klebsiella pneumoniae) and positive (Bacillus subtilis) strains. Results show that all four sweeteners exhibit antimicrobial effects on these strains. The antimicrobial mechanism is due to increased reactive oxygen species (ROS) and cell envelope damage. Compared to sucrose and glucose, the treatment of artificial sweeteners stimulates bacterial efflux pumps and promotes bacterial evolution of antibiotic tolerance. Collectively, our finding provides insights into roles of artificial sweeteners in the emergence of antibiotic tolerance and calls for a re-evaluation of risks due to their intensive usage.202235398799
860180.9974Herbicide promotes the conjugative transfer of multi-resistance genes by facilitating cellular contact and plasmid transfer. The global dissemination of antibiotic resistance genes (ARGs), especially via plasmid-mediated horizontal transfer, is becoming a pervasive health threat. While our previous study found that herbicides can accelerate the horizontal gene transfer (HGT) of ARGs in soil bacteria, the underlying mechanisms by which herbicides promote the HGT of ARGs across and within bacterial genera are still unclear. Here, the underlying mechanism associated with herbicide-promoted HGT was analyzed by detecting intracellular reactive oxygen species (ROS) production, extracellular polymeric substance composition, cell membrane integrity and proton motive force combined with genome-wide RNA sequencing. Exposure to herbicides induced a series of the above bacterial responses to promote HGT except for the ROS response, including compact cell-to-cell contact by enhancing pilus-encoded gene expression and decreasing cell surface charge, increasing cell membrane permeability, and enhancing the proton motive force, providing additional power for DNA uptake. This study provides a mechanistic understanding of the risk of bacterial resistance spread promoted by herbicides, which elucidates a new perspective on nonantibiotic agrochemical acceleration of the HGT of ARGs.202234969463
834590.9974Antibiotic Resistance via Bacterial Cell Shape-Shifting. Bacteria have evolved to develop multiple strategies for antibiotic resistance by effectively reducing intracellular antibiotic concentrations or antibiotic binding affinities, but the role of cell morphology in antibiotic resistance remains poorly understood. By analyzing cell morphological data for different bacterial species under antibiotic stress, we find that bacteria increase or decrease the cell surface-to-volume ratio depending on the antibiotic target. Using quantitative modeling, we show that by reducing the surface-to-volume ratio, bacteria can effectively reduce the intracellular antibiotic concentration by decreasing antibiotic influx. The model further predicts that bacteria can increase the surface-to-volume ratio to induce the dilution of membrane-targeting antibiotics, in agreement with experimental data. Using a whole-cell model for the regulation of cell shape and growth by antibiotics, we predict shape transformations that bacteria can utilize to increase their fitness in the presence of antibiotics. We conclude by discussing additional pathways for antibiotic resistance that may act in synergy with shape-induced resistance.202235616332
8497100.9974Conjugation-mediated transfer of antibiotic resistance genes influenced by primary soil components and underlying mechanisms. Soil is the main natural reservoir of antibiotic resistant bacteria and antibiotic resistance genes (ARGs). Their dissemination and proliferation were largely motivated by conjugative transfer, while the influence of soil components on bacterial conjugative transfer and the underlying mechanisms remain poorly understood. In the present study, two Escherichia coli strains were exposed to soil minerals (quartz, kaolinite and montmorillonite) and organic matters (humic acid, biochar and soot) respectively to investigate their impact on ARGs conjugation. The results showed that quartz had no significant effect on conjugation; montmorillonite promoted the growth of the donor, but inhibited the recipient and conjugant; kaolinite and three organic matters significantly promoted the production of conjugant, while biochar promoted and then inhibited it with time prolong. Within the range of bacterial concentration involved in this study, the concentration of conjugant increased with the ratio of the concentration of donor and recipient (R(D/R)), indicating that the variation of conjugant production was mainly mediated by changing R(D/R). Further observation of biochar treatment group showed that the bacterial responses such as cell membrane permeability, cell surface hydrophobicity and biofilm formation ability shifted with the exposure time, which might be a potential factor affecting conjugative transfer. Collectively, our findings suggest that the type and exposure time of soil components jointly affected conjugation, while the change of R(D/R) and related bacterial responses are the main underlying mechanisms.202336586689
7925110.9974Effects comparison between the secondary nanoplastics released from biodegradable and conventional plastics on the transfer of antibiotic resistance genes between bacteria. Antibiotic resistance genes (ARGs) have caused widespread concern because of their potential harm to environmental safety and human health. As substitutes for conventional plastics, the toxic effects of short-term degradation products of biodegradable plastics (polylactic acid (PLA) and polyhydroxyalkanoates (PHA)) on bacteria and their impact on ARGs transfer were the focus of this study. After 60 days of degradation, more secondary nanoplastics were released from the biodegradable plastics PLA and PHA than that from the conventional plastics polystyrene (PS). All kinds of nanoplastics, no matter released from biodegradable plastics or conventional plastics, had no significant toxicity to bacteria. Nanoplastic particles from biodegradable plastics could significantly increase the transfer efficiency of ARGs. Although the amount of secondary nanoplastics produced by PHA microplastics was much higher than that of PLA, the transfer frequency after exposure to PLA was much higher, which may be due to the agglomeration of PHA nanoplastics caused by plastic instability in solution. After exposure to the 60 d PLA nanoplastics, the transfer frequency was the highest, which was approximately 28 times higher than that of control. The biodegradable nanoplastics significantly enhanced the expression of the outer membrane pore protein genes ompA and ompC, which could increase cell membrane permeability. The expression levels of trfAp and trbBp were increased by repressed major global regulatory genes korA, korB, and trbA, which eventually led to an increase in conjugative transfer frequency. This study provides important insights into the evaluation of the environmental and health risks caused by secondary nanoplastics released from biodegradable plastics.202336414161
8522120.9974Electrochemical disinfection may increase the spread of antibiotic resistance genes by promoting conjugal plasmid transfer. Current in the milliampere range can be used for electrochemical inactivation of bacteria. Yet, bacteria-including antibiotic resistant bacteria (ARB) may be subjected to sublethal conditions due to imperfect mixing or energy savings measures during electrochemical disinfection. It is not known whether such sublethal current intensities have the potential to stimulate plasmid transfer from ARB. In this study, conjugal transfer of plasmid pKJK5 was investigated between Pseudomonas putida strains under conditions reflecting electrochemical disinfection. Although the abundance of culturable and membrane-intact donor and recipient cells decreased with applied current (0-60 mA), both transconjugant density and transconjugant frequency increased. Both active chlorine and superoxide radicals were generated electrolytically, and ROS generation was induced. In addition, we detected significant over expression of a core oxidative stress defense gene (ahpCF) with current. Expression of selected conjugation related genes (traE, traI, trbJ, and trbL) also significantly correlated with current intensity. ROS accumulation, SOS response and subsequent derepression of conjugation are therefore the plausible consequence of sublethal current exposure. These findings suggest that sublethal intensities of current can enhance conjugal plasmid transfer, and that it is essential that conditions of electrochemical disinfection (applied voltage, current density, time and mixing) are carefully controlled to avoid conjugal ARG transmission.202336328265
8564130.9974Effects of functional modules and bacterial clusters response on transmission performance of antibiotic resistance genes under antibiotic stress during anaerobic digestion of livestock wastewater. The formation and transmission of antibiotic resistance genes (ARGs) have attracted increasing attention. It is unclear whether the internal mechanisms by which antibiotics affect horizontal gene transfer (HGT) of ARGs during anaerobic digestion (AD) were influenced by dose and type. We investigated the effects of two major antibiotics (oxytetracycline, OTC, and sulfamethoxazole, SMX) on ARGs during AD according to antibiotic concentration in livestock wastewater influent. The low-dose antibiotic (0.5 mg/L) increased ROS and SOS responses, promoting the formation of ARGs. Meanwhile, low-dose antibiotics could also promote the spread of ARGs by promoting pili, communication responses, and the type IV secretion system (T4SS). However, different types and doses of antibiotics would lead to changes in the above functional modules and then affect the enrichment of ARGs. With the increasing dose of SMX, the advantages of pili and communication responses would gradually change. In the OTC system, low-dose has the strongest promoting ability in both pili and communication responses. Similarly, an increase in the dose of SMX would change T4SS from facilitation to inhibition, while OTC completely inhibits T4SS. Microbial and network analysis also revealed that low-dose antibiotics were more favorable for the growth of host bacteria.202336063716
8329140.9973Protozoan predation enhances stress resistance and antibiotic tolerance in Burkholderia cenocepacia by triggering the SOS response. Bacterivorous protists are thought to serve as training grounds for bacterial pathogens by subjecting them to the same hostile conditions that they will encounter in the human host. Bacteria that survive intracellular digestion exhibit enhanced virulence and stress resistance after successful passage through protozoa but the underlying mechanisms are unknown. Here we show that the opportunistic pathogen Burkholderia cenocepacia survives phagocytosis by ciliates found in domestic and hospital sink drains, and viable bacteria are expelled packaged in respirable membrane vesicles with enhanced resistance to oxidative stress, desiccation, and antibiotics, thereby contributing to pathogen dissemination in the environment. Reactive oxygen species generated within the protozoan phagosome promote the formation of persisters tolerant to ciprofloxacin by activating the bacterial SOS response. In addition, we show that genes encoding antioxidant enzymes are upregulated during passage through ciliates increasing bacterial resistance to oxidative radicals. We prove that suppression of the SOS response impairs bacterial intracellular survival and persister formation within protists. This study highlights the significance of protozoan food vacuoles as niches that foster bacterial adaptation in natural and built environments and suggests that persister switch within phagosomes may be a widespread phenomenon in bacteria surviving intracellular digestion.202438366016
8337150.9973Dynamic Boolean modelling reveals the influence of energy supply on bacterial efflux pump expression. Antimicrobial resistance (AMR) is a global health issue. One key factor contributing to AMR is the ability of bacteria to export drugs through efflux pumps, which relies on the ATP-dependent expression and interaction of several controlling genes. Recent studies have shown that significant cell-to-cell ATP variability exists within clonal bacterial populations, but the contribution of intrinsic cell-to-cell ATP heterogeneity is generally overlooked in understanding efflux pumps. Here, we consider how ATP variability influences gene regulatory networks controlling expression of efflux pump genes in two bacterial species. We develop and apply a generalizable Boolean modelling framework, developed to incorporate the dependence of gene expression dynamics on available cellular energy supply. Theoretical results show that differences in energy availability can cause pronounced downstream heterogeneity in efflux gene expression. Cells with higher energy availability have a superior response to stressors. Furthermore, in the absence of stress, model bacteria develop heterogeneous pulses of efflux pump gene expression which contribute to a sustained sub-population of cells with increased efflux expression activity, potentially conferring a continuous pool of intrinsically resistant bacteria. This modelling approach thus reveals an important source of heterogeneity in cell responses to antimicrobials and sheds light on potentially targetable aspects of efflux pump-related antimicrobial resistance.202235078338
9162160.9973Joint effects of antibiotics and quorum sensing inhibitors on resistance development in bacteria. Quorum sensing inhibitors (QSIs) are promising alternatives to antibiotics. While QSIs have great application potential in a variety of fields, their joint effects with antibiotics on bacteria, especially on antibiotic resistance mutations, remain largely unexplored. Herein, we report the joint effects of four commonly used antibiotics and two QSIs on bacterial growth and resistance mutations in E. coli. It was found that QSIs presented antagonistic or additive effects with antibiotics on bacterial growth, and more importantly, QSIs exhibited an attenuating effect on antibiotic-induced resistance mutations. Further analysis demonstrated that antibiotics might enhance resistance mutations by promoting the expressions of rpoS, lexA and recA, while QSIs attenuated the mutations by promoting the expressions of mutS and uvrD. The present research provides a comprehensive understanding of the joint effects of antibiotics and QSIs on bacteria, which may benefit the risk assessment of their combined exposure.202134060581
8960170.9973Pyraclostrobin induces multi-antibiotic resistance in Escherichia coli via quorum sensing: A new perspective. Antibiotic resistance seriously threatens to global public health, and non-antibiotic chemicals like pesticides can contribute to its development. Quorum sensing (QS) is an intercellular communication system that regulates group behavior and can potentially become a pathway for the development of antibiotic resistance. This study firstly discovered that exposure to pyraclostrobin at 0.5 mg/L activated QS, resulting in antibiotic resistance in Escherichia coli, with minimum inhibitory concentrations (MICs) increasing by up to 128-fold against tested antibiotics. Mechanistically, the high expression of the luxS gene induced by pyraclostrobin stress increased the level of the QS signal molecule (AI-2), leading to enhanced QS in antibiotic-resistant bacteria (ARB), thereby upregulating the expression of multidrug efflux pump genes (acrB and marA) and downregulating the expression of outer membrane porin genes (ompC and ompF). Meanwhile, using a QS inhibitor also increased the strains' antibiotic sensitivity. Additionally, pyraclostrobin exposure damaged cell membranes, induced oxidative stress, and caused gene mutations, further promoting multidrug resistance. Overall, the findings demonstrate that pyraclostrobin exposure can stimulate antibiotic resistance in Escherichia coli by activating QS and inducing gene mutations. Therefore, the rigorous application of fungicides is essential to retard the development of antibiotic resistance.202540544772
8623180.9973Antidepressants promote the spread of antibiotic resistance via horizontally conjugative gene transfer. Antibiotic resistance is a global concern threatening public health. Horizontal gene transfer (HGT) between bacterial species contributes greatly to the dissemination of antibiotic resistance. Conjugation is one of the major HGT pathways responsible for the spread of antibiotic resistance genes (ARGs). Antidepressant drugs are commonly prescribed antipsychotics for major depressive disorders and are frequently detected in aquatic environments. However, little is known about how antidepressants stress bacteria and whether such effect can promote conjugation. Here, we report that commonly prescribed antidepressants, sertraline, duloxetine, fluoxetine, and bupropion, can promote the conjugative transfer of plasmid-borne multidrug resistance genes carried by environmentally and clinically relevant plasmids. Noteworthy, the transfer of plasmids across bacterial genera is significantly enhanced by antidepressants at clinically relevant concentrations. We also reveal the underlying mechanisms of enhanced conjugative transfer by employing flow cytometric analysis, genome-wide RNA sequencing and proteomic analysis. Antidepressants induce the production of reactive oxygen species and the SOS response, increase cell membrane permeability, and upregulate the expression of conjugation relevant genes. Given the contribution of HGT in the dissemination of ARGs, our findings highlight the importance of prudent prescription of antidepressants and to the potential connection between antidepressants and increasing antibiotic resistance.202236054646
8539190.9973Effects of quaternary ammonium disinfectants on human pathogenic bacteria in anaerobic sludge digestion: Dose-response and resistance variation. Sewage sludge is a critical reservoir for biological pollutants, and its harmless disposal remains a major issue. Quaternary ammonium compounds (QACs) as typical household disinfectants are inevitably concentrated in sewage sludge, and have the potential to affect human pathogenic bacteria (HPBs) that remain poorly understood. This study found that the relative abundance of HPBs in digesters was decreased by 10 - 20 % at low QACs dose, but increased by 238 - 591 % at high QACs dose. Mechanistic analysis revealed that low QACs doses promoted functional hydrolytic/fermentative bacteria and their metabolism by stimulating extracellular polymeric substances secretion and enhancing resistance to QACs. Conversely, high QAC doses decreased microbial biomass and developed QACs and antibiotic resistance of HPBs by increasing cell membrane permeability and triggering oxidative stress, resulting in deteriorating sanitation performance. These findings provide advanced insights into the potential function and hazards of exogenous QACs on the biosafety of digestate.202539505280