Propagation Of Antibiotic Resistance Genes Research Articles

Hydrometeorological Influence on Antibiotic‐Resistance Genes (ARGs) and Bacterial Community at a Recreational Beach in Korea

We investigated the occurrence and distribution of antibiotic‐resistance genes (ARGs) and the composition of a bacterial community under conditions of rainfall on a recreational beach in Korea. Seawater samples, collected every 1‒5 hours in June 2018 and May 2019, were analyzed using quantitative real-time polymerase chain reaction and next-generation sequencing. We found a substantial influence of rainfall and tidal levels on the relative abundance of total ARGs and bacterial operational taxonomic units (OTUs), which showed 1.9 × 103 and 1.1 × 101 fold increases, respectively. In particular, the elevated levels of ARGs were maintained for up to 32 hours after rainfall. An increased abundance of sewage‐related ARGs and bacterial OTUs suggested that combined sewer overflow (CSO) may be the major factor contributing to the increase in the number and diversity of ARGs and related bacterial communities. Network analysis of ARGs and OTUs indicated that, at the genus level, Acinetobacter, Pseudomonas, and Prevotella were the main potential pathogens carrying the observed ARGs in the recreational seawater. Overall, these findings highlight the potential threat to public health on beaches, and indicate the requirement for more adequate monitoring, with greater efforts to mitigate the propagation of ARGs arising from CSOs.

CeO2 Nanoparticles Regulate the Propagation of Antibiotic Resistance Genes by Altering Cellular Contact and Plasmid Transfer.

The dissemination and propagation of antibiotic resistance genes (ARGs) via plasmid-mediated conjugation pose a major threat to global public health. The potential effects of nanomaterials on ARGs fates have drawn much attention recently. In this study, CeO2 nanoparticles (NPs), one of the typical nanomaterials proposed for increasing crop production, were applied at the concentration range of 1-50 mg/L to investigate their effects on ARGs transfer between Escherichia coli. Our results revealed that the conjugative transfer of RP4 plasmid was enhanced by 118-123% at relatively high concentrations (25 and 50 mg/L) of CeO2 NPs, however, CeO2 NPs at low concentrations (1 and 5 mg/L) inhibited the transfer by 22-26%. The opposite effect at low concentrations is mainly attributed to (i) the reduced ROS level, (ii) the weakened intercellular contact via inhibiting the synthesis of polysaccharides in extracellular polymeric substances, and (iii) the down-regulated expression of plasmid transfer genes due to the shortage of ATP supply. Our findings highlight the distinct dose-dependent responses of ARGs conjugative transfer, providing evidence for selecting appropriate NPs dose to reduce the spread of ARGs while applying nanoagrotechnology.

Vessel transport of antibiotic resistance genes across oceans and its implications for ballast water management

The emergence and spread of antibiotic resistance are major threats to ecosystems and human health. Transoceanic channels (e.g., ship ballast water) can transfer harmful aquatic organisms across geographically isolated waters. However, the occurrence of antibiotic resistance genes (ARGs) in ship ballast water and their relationship with microbial communities and environmental factors remain unknown. In this study, ballast water from 28 vessels sailing to Shanghai and Jiangyin (China) were collected, and the ARGs in these water samples were investigated. Considerable levels of ARGs and integrase of the class-I integrons (intI1) were detected in all ballast water samples. sul1 and tetQ were the most and least abundant ARGs in ballast water samples, respectively. The ARGs were strongly correlated with those of the 16S rRNA and intI1 genes. Ballast water exchange can reduce the absolute abundance of some kinds of ARGs while increasing the relative abundance of several ARGs (e.g., mefA, mexF, strB, sul1, and tetQ). Moreover, the bacterial hosts of ARGs were generally different in the unexchanged ballast water (UEBW) and exchanged ballast water (EBW). In particular, Leisingera and unclassified_Erythrobacteraceae were the main ARGs-associated genera in the EBW, while Pseudohongiella, Cycloclasticus, OM43_clade, norank_f_Rhodospirillaceae, and norank_f_Rhodobacteraceae were the dominant ARGs hosts in the UEBW. Overall, ship ballast water is an effective moving carrier for the global transference of ARGs, and its sufficient management is required for mitigating ARGs propagation across oceans.

Antibiotic resistance genes and bacterial community dynamics in the seawater environment of Dapeng Cove, South China

In recent years, the propagation of antibiotic resistance genes (ARGs) and increased antibiotic resistance in pathogens have gained serious attention. Numerous reports have investigated the influence of domestic sewage discharge, medical wastewater and aquaculture wastewater on rivers and lakes, while the dynamics of ARGs in seawater and the relationships between ARGs, bacterial community structure and environmental factors have been less thoroughly described. In this study, the abundance, distribution and source of ARGs, as well as the relationships between ARGs, bacterial community changes and environmental factors in the seawater environment and sediment of Dapeng Cove, were investigated. Real-time quantitative PCR and Illumina Miseq sequencing technology were applied to determine the effects of the production cycle of cage culture, tourism and seasonality on ARGs. Chloramphenicol resistance genes (floR, cmlA) and sulfonamide resistance genes (sul1) were the dominant resistance genes in water and sediment. Pearson's correlation analysis showed that the abundance of all ARGs and the integrase I gene intI1 was positively correlated with chemical oxygen demand and suspended solids. Class 1 integrons might facilitate the dissemination of ARGs, and intI1 was detected in all samples at high concentrations. In aqueous environments, Cyanobacteria, Proteobacteria and Bacteroidetes were the dominant phyla, among which Proteobacteria and Bacteroidetes were positively correlated with the concentration of target ARGs. In the sediment, Proteobacteria, Bacteroidetes, Chloroflexi, Acidobacteria and Planctomycetes were the dominant phyla, among which Bacteroidetes and Planctomycetes were positively correlated with most of the target ARGs and had a significant influence on changes in the abundance of ARGs. The domestic sewage was the main source of ARGs in the seawater. Our results showed that bacterial community structure and environmental factors affected the distributional dynamics of ARGs. Anthropogenic activities played significant roles in promoting ARGs abundance in the seawater environments.

Propagation of antibiotic resistance genes in an industrial recirculating aquaculture system located at northern China

The increasing prevalence and spread of antibiotic resistance genes (ARGs) in intensive aquaculture environments are of great concern to food safety and public health. However, the level of ARGs and their potential propagation factors in an industrial recirculating aquaculture system (RAS) have not previously been comprehensive explored. In this study, the levels of 14 different ARG markers and 2 kinds of mobile genetic elements (MGEs) were investigated in a RAS (including water, fish, feces, pellet feed meal, and biofilm samples) located northern China. qnrA, qnrB, qnrS, qepA, aac(6′)-Ib, and floR were dominant ARGs, which average concentration levels were presented at 4.51–7.74 copies/L and 5.36–13.07 copies/g, respectively, suggesting that ARGs were prevalent in RAS with no recorded history of antibiotic use. Elevated level of ARGs was found in water of RAS even after the final UV treatment compared with its influent. In RAS, Proteobacteria, Verrucomicrobia, Bacteroidetes, and Planctomycetes were the predominant phyla. Notably, elevated levels of potential opportunistic pathogens were observed along with abundant ARGs suggesting an increasing risk of capturing ARGs and MGEs for human pathogens. This study has revealed for the first time that reared fish, their feces, pellet feed meal as the introduction sources and the selection roles of treatment units co-driven the ARG profile, and the co-selection of water environmental factors and their consequently induced bacterial community shifts formed by their influence are the determining drivers for the ARG propagation in RAS.

Behavior of nitrogen, phosphorus and antibiotic resistance genes under polyvinyl chloride microplastics pressures in an aerobic granular sludge system

Polyvinyl chloride (PVC) is the common microplastics (MPs) detected in wastewater treatment plants causing harmful effects on organisms. However, the effects of PVC MPs on an aerobic granular sludge (AGS) system is not clear. In present study, the behavior of nitrogen, phosphorus and antibiotic resistance genes (ARGs) under PVC MPs pressure in an AGS system was investigated. Results showed PVC MPs promoted the phosphorus release and uptake of polyphosphate accumulating organisms (PAOs) and reduced total inorganic nitrogen removal efficiency. Extracellular polymeric substances were positively linked to PVC MPs. Moreover, PVC MPs increased the abundance of PAOs and Nitrospira, but decreased the abundance of denitrifying bacteria. The propagation of intI1 and tetE could be facilitated by PVC MPs, and the main antibiotic resistance mechanism of AGS system was the efflux pump. Chloroffexi, Actinobacteria, Bacteroidetes and Nitrospirae hold higher tolerance to PVC MPs than Proteobacteria. Network analysis showed PVC MPs positively correlated with some Accumulibacter clades and ARGs. This study indicated PVC MPs inhibited nitrogen removal and benefited ARGs propagation, which need to cause great concern.

Natural sphalerite nanoparticles can accelerate horizontal transfer of plasmid-mediated antibiotic-resistance genes

Minerals and microorganisms are integral parts of natural environments, and they inevitably interact. Antibiotic-resistance genes (ARGs) significantly threaten modern healthcare. However, the effects of natural minerals on ARG propagation in aquatic systems are not fully understood. The present work studied the effects of natural sphalerite (NS) nanoparticles on the horizontal transfer of ARGs from Escherichia coli DH5α (CTX) (donor) to E. coli C600 (Sm) (recipient), and from E. coli DH5α (MCR) (donor) to E. coli C600 (Sm), and their underlying mechanisms. NS particles (0.5–50 mg L−1) induced an NS-concentration-dependent increase in conjugative transfer frequency. The underlying mechanisms associated with the facilitated ARG transfer included the production of intracellular reactive oxygen species, the SOS response, changes in bacterial cell morphology, and alteration of mRNA levels of bacterial cell membrane protein-related genes and genes associated with conjugative ARG transfer. The information herein offers new mechanistic understanding of risks of bacterial resistance resulting from NS.

Ionic Liquid Enriches the Antibiotic Resistome, Especially Efflux Pump Genes, Before Significantly Affecting Microbial Community Structure.

An expanding list of chemicals may permeabilize bacterial cells and facilitate horizontal gene transfer (HGT), which enhances propagation of antibiotic resistance genes (ARGs) in the environment. Previous studies showed that 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm][PF6]), an ionic liquid, can facilitate HGT of some ARGs among bacteria. However, the dynamic response of a wider range of ARGs and associated mobile genetic elements (MGEs) in different environments is unknown. Here, we used metagenomic tools to study shifts of the resistome and microbiome in both sediments and freshwater microcosms exposed to [BMIm][PF6]. Exposure for 16 h to 0.1 or 1.0 g/L significantly enriched more than 207 ARG subtypes primarily encoding efflux pumps in freshwater microcosms as well as cultivable antibiotic-resistant bacteria. This resistome enrichment was attributed to HGT facilitated by MGEs (428 plasmids, 61 integron-integrase genes, and 45 gene cassettes were enriched) as well as to HGT-related functional genes. Interestingly, resistome enrichment occurred fast (within 16 h) after [BMIm][PF6] exposure, before any significant changes in bacterial community structure. Similar ARG enrichment occurred in sediment microcosms exposed to [BMIm][PF6] for 28 d, and this longer exposure affected the microbial community structure (e.g., Proteobacteria abundance increased significantly). Overall, this study suggests that [BMIm][PF6] releases could rapidly enrich the antibiotic resistome in receiving environments by increasing HGT and fortuitously selecting for efflux pump genes, thus contributing to ARG propagation.

(Nano)microplastics promote the propagation of antibiotic resistance genes in landfill leachate

Municipal landfill leachate is a huge reservoir of (nano)microplastics (N/MPs) and antibiotic resistance genes (ARGs).

Exploring the antibiotic resistome in activated sludge and anaerobic digestion sludge in an urban wastewater treatment plant via metagenomic analysis.

Antibiotic resistance genes (ARGs) are emerging contaminants that pose a potential threat to human health worldwide. Urban wastewater treatment plants (WWTPs) are a main source of both antibiotic-resistant bacteria and ARGs released into the environment. Nevertheless, the propagation of ARGs and their underlying mechanisms and the dynamics of mobile genetic elements (MGEs) in WWTPs have rarely been investigated in South Korea. In this study, shotgun metagenomic analysis was used to identify comprehensive ARGs and their mechanisms, bacterial communities, and MGEs from 4 configurations with 2 activated sludge (AS) and 2 anaerobic digestion sludge (ADS) samples. A total of 181 ARG subtypes belonging to 22 ARG types were broadly detected, and the ARG abundances in the AS samples were 1.3-2.0 orders of magnitude higher than in the ADS samples. Multidrug and bacitracin resistance genes were the predominant ARG types in AS samples, followed by ARGs against sulfonamide, tetracycline, and β-lactam. However, the composition of ARG types in ADS samples was significantly changed. The abundance of multidrug and β-lactam resistance genes was drastically reduced in the ADS samples. The resistance genes of MLS were the predominant, followed by ARGs against sulfonamide and tetracycline in the ADS samples. In addition, plasmids were the dominant MGEs in the AS samples, while integrons (intI1) were the dominant MGEs in the ADS samples. These results provide valuable information regarding the prevalence of ARG types and MGEs and the difference patterns between the AS and ADS systems.

Antibiotic Resistance Genes in drinking water of China: Occurrence, distribution and influencing factors

Drinking water samples were collected from 71 cities, including 28 provincial capital cities or municipalities, 20 prefecture cities and 23 counties, of 31 provincial-level administrative regions in China from July to August in 2017. Futhermore, 24 Antibiotic Resistance Genes (ARGs), 16S rRNA and 2 integrase genes were quantified by qPCR to investigate the pollution degree of ARGs. The results revealed that the 16S ranged from 105 – 108 copies/100 mL in the drinking water, and its treatment process could effectively remove bacteria. Moreover, sulfonamides-ARGs were the most prevalent ARGs in the drinking water of China, and the abundance of blaTEM ranked top five in all cities among the selected ARGs, indicating that the pollution condition of the genes should be aroused more attention. The data of qPCR and correlation analyses indicated that intI1 played a more crucial role than intI2 in the propagation of ARGs in the drinking water. Additionally, the pollution degree of ARGs among different city types showed no significant difference.

Occurrence of antibiotics and antibiotic resistance genes and their correlations in lower Yangtze River, China

The overuse and misuse of antibiotics could promote the emergence of antibiotic resistance genes (ARGs) and pose a potential risk to human health and the ecological environment. In this study, fifteen antibiotics and their corresponding ARGs in water, sediment and sewage treatment plant (STP) effluent were analysed to investigate their occurrence and correlation in the Yangtze River (Jiangsu section) for the first time. The concentrations of erythromycin-H2O (EM-H2O) (2.08–30 ng L−1) and ofloxacin (OFL) (290–8400 ng kg−1) were the highest in the water and sediment, respectively, and EM-H2O and clarithromycin (CLA) posed the highest risks to aquatic organisms. The concentrations of antibiotics in STP effluent were significantly higher (p < 0.05) than those in the water. Norfloxacin (NOR) was the most predominant antibiotic, with low removal efficiency (−38%-51%), in STPs; the concentration of NOR in the STP effluent was 4–6 orders of magnitude higher than that in the water. Moreover, the concentrations of antibiotics and their corresponding ARG abundance in downstream were higher than those in upstream, suggesting that STPs with high concentration levels might be an important source of river contamination. Additionally, the concentrations of antibiotics and the abundance of ARGs might increase after the sewage treatment process. The results also showed the prevalence of sul1 and sul2 in all the sampling sites. Significant correlations (p < 0.0001) were detected between int1 and sul1 and sul2, which resulted from the contribution of int1 to the propagation of ARGs. Overall, this study demonstrated the prevalence of antibiotics and ARGs and their inconsistent correlations in the Yangtze River (Jiangsu section) and provides support for further investigation of the occurrence and spread of antibiotics and ARGs.

Potential impacts of horizontal gene transfer on human health and physiology and how anthropogenic activity can affect it.

Horizontal gene transfer (HGT) is widespread among prokaryotes driving their evolution. In this paper, we review the potential impact in humans of the HGT between prokaryotes living in close association with humans in two scenarios: horizontal transfer in human microbiomes and transfer between microbes living in human managed environments. Although our vision is focused on the possible impact of these transfers in the propagation of antibiotic resistance genes or pathogenicity determinants, we also discuss possible human physiological adaptations via gene transfer between resident and occasional bacteria in the human microbiome.

Seasonal variations in antibiotic resistance genes in estuarine sediments and the driving mechanisms

Estuary sediments are chemically contaminated by adjacent coastal industrial cities, but the impact of organic pollutants on antibiotic resistance genes (ARGs) in estuarine sediments is unknown. We comprehensively analyzed the complex interactions between chemical pollutants (heavy metals and organic pollutants), mobile genetic elements (MGEs), and ARGs in estuarine sediments during various seasons. The results indicate that under the effects of the chemically polluted river water, the number of different estuarine sediment ARGs increased by 76.9%–92.3% in summer and 5.9%–35.3% in winter, and the abundance of these ARGs increased by 29–5195 times in summer and 48–239 times in winter. The abundance of sediment ARGs in distinct estuaries showed different seasonal trends. Seasonal changes had a greater impact on the abundance of estuarine sediment ARGs than on their diversity. The diversity of estuarine sediment ARGs was positively correlated with the chemical pollution levels. Furthermore, chemical pollution was positively correlated with MGEs, and MGEs were correlated with ARG abundance. These results indicate that ARGs are enriched in bacteria via horizontal gene transfer triggered by chemical pollution, promoting multi-antibiotic resistance in estuarine sediment bacteria. These findings have implications for our understanding of the distribution and propagation of ARGs in chemically polluted estuarine sediments.

Effect and mechanism of quorum sensing on horizontal transfer of multidrug plasmid RP4 in BAC biofilm

The widespread emergence of antibiotic resistance genes (ARGs) in drinking water systems endangers human health, and may be exacerbated by their horizontal gene transfer (HGT) among microbiota. In our previous study, Quorum sensing (QS) molecules produced by bacteria from biological activated carbon (BAC) biofilms were demonstrated to influence the transfer efficiency of a model conjugative plasmid, here RP4. In this study, we further explored the effect and mechanism of QS on conjugation transfer. The results revealed that Acyl-homoserine lactones producing (AHL-producing) bacteria isolated from BAC biofilm play a role in the propagation of ARGs. We selected several quorum sensing inhibitors (QSIs) to study their effects on AHL-producing bacteria, including the formation of biofilm and the regulating effect on conjugation transfer. In addition, the possible molecular mechanisms for AHLs that promote conjugative transfer were attributable to enhancing the mRNA expression, which involved altered expressions of conjugation-related genes. We also found that QSIs could inhibit conjugative transfer by downregulating the conjugation-relevant genes. We believe that this is the first insightful exploration of the mechanism by which AHLs will facilitate and QSIs will inhibit the conjugative transfer of ARGs. These results provide creative insight into ARG pollution control that involves blocking QS during BAC treatment in drinking water systems.

Distribution of antibiotic resistance genes in soil amended using Azolla imbricata and its driving mechanisms.

The floating aquatic plant of Azolla imbricata has an outstanding purification capability for polluted river water, and it is also employed to improve soil fertility. However, the occurrence and distribution of antibiotic resistance genes (ARGs) in soil amended using A.imbricata remain unclear. In the soil amendment with A. imbricata, heavy metals, antibiotics, transposase genes, ARGs, and bacterial communities in the soil were determined in this study. The results indicated that the diversity of bacteria and ARGs increased, while the diversity of ARGs decreased under the amendment using an appropriate amount of A. imbricata. The Firmicutes, Chloroflexi, Actinobacteria, and Cyanobacteria were the main host bacteria of ARGs. The vertical gene transfer of ARGs was weak, and the horizontal gene transfer became the dominant transfer pathway of ARGs. The amendment with A. imbricata altered the distribution of heavy metals, antibiotics, transposase genes, ARGs, and dominant bacteria. The amendment using A. imbricata promoted the degradation of antibiotics, decreased the concentrations of available heavy metals, and eliminated the abundance of ARGs and transposase genes. Our findings suggested a comprehensive effect of multiple stresses on the fate of ARGs in soil amended with A. imbricata, providing an insight into the distribution and propagation of ARGs in soil amended using plant residues.

Shifting interactions among bacteria, fungi and archaea enhance removal of antibiotics and antibiotic resistance genes in the soil bioelectrochemical remediation

BackgroundAntibiotics and antibiotic resistance genes (ARGs) are two pollutants in soil, especially ARGs as one of the top three threats to human health. The performance of soil microbial fuel cells (MFCs) fuelled with antibiotics was investigated.ResultsIn this study, soil MFCs spiked with tetracycline exhibited optimal bioelectricity generation, which was 25% and 733% higher than those of MFCs spiked with sulfadiazine and control, respectively. Compared with the non-electrode treatment, not only did functional micro-organisms change in open- and closed-circuit treatments, but also the microbial affinities, respectively, increased by 50% and 340% to adapt to higher removal of antibiotics. For the open-circuit treatment, the ineffective interspecific relation of micro-organisms was reduced to assist the removal efficiency of antibiotics by 7–27%. For the closed-circuit treatment, an intensive metabolic network capable of bioelectricity generation, degradation and nitrogen transformation was established, which led to 10–35% higher removal of antibiotics. Importantly, the abundances of ARGs and mobile genetic element (MGE) genes decreased after the introduction of electrodes; especially in the closed-circuit treatment, the highest reduction of 47% and 53% was observed, respectively.ConclusionsSoil MFCs possess advantages for the elimination of antibiotics and ARGs with sevenfold to eightfold higher electricity generation than that of the control treatment. Compared with sulphonamides, the enhancement removal of tetracycline is higher, while both potential ARG propagation risk is reduced in soil MFCs. This study firstly synchronously reveals the relationships among bacteria, fungi and archaea and with ARGs and MGE genes in soil bioelectrochemical systems.

CO2 promotes the conjugative transfer of multiresistance genes by facilitating cellular contact and plasmid transfer

The dissemination of antibiotic resistance genes (ARGs), especially via the plasmid-mediated conjugation, is becoming a pervasive global health threat. This study reported that this issue can be worse by CO2, as increased CO2 was found to facilitate the conjugative transfer of ARGs carried on plasmid RP4 by 2.4–9.0 and 1.3–3.8 fold within and across genera, respectively. Mechanistic studies revealed that CO2 benefitted the cell-to-cell contact by increasing cell surface hydrophobicity and decreasing cell surface charge, both of which resulted in the reduced intercellular repulsion. Besides, the transcriptional expression of genes responsible for global regulator (korA, korB and trbA), plasmid transfer and replication system (trfAp), and mating pair formation system (traF and traG) were all influenced by CO2, facilitating the mobilization and channel transfer of plasmid. Furthermore, the presence of CO2 induced the release of intracellular Ca2+ and increased the transmembrane potential of recipients, which contributed to the increased proton motive force (PMF), providing more power for DNA uptake. This is the first study addressing the potential risks of increased CO2 on the propagation of ARGs, which provides a new insight into the concerns of anthropogenic CO2 emissions and CO2 storage.

Oral Beta-Lactamase Protects the Canine Gut Microbiome from Oral Amoxicillin-Mediated Damage

Antibiotics damage the gut microbiome, which can result in overgrowth of pathogenic microorganisms and emergence of antibiotic resistance. Inactivation of antibiotics in the small intestine represents a novel strategy to protect the colonic microbiota. SYN-004 (ribaxamase) is a beta-lactamase formulated for oral delivery intended to degrade intravenously administered beta-lactam antibiotics in the gastrointestinal (GI) tract. The enteric coating of ribaxamase protects the enzyme from stomach acid and mediates pH-dependent release in the upper small intestine, the site of antibiotic biliary excretion. Clinical benefit was established in animal and human studies in which ribaxamase was shown to degrade ceftriaxone in the GI tract, thereby preserving the gut microbiome, significantly reducing Clostridioides difficile disease, and attenuating antibiotic resistance. To expand ribaxamase utility to oral beta-lactams, delayed release formulations of ribaxamase, SYN-007, were engineered to allow enzyme release in the lower small intestine, distal to the site of oral antibiotic absorption. Based on in vitro dissolution profiles, three SYN-007 formulations were selected for evaluation in a canine model of antibiotic-mediated gut dysbiosis. Dogs received amoxicillin (40 mg/kg, PO, TID) +/- SYN-007 (10 mg, PO, TID) for five days. Serum amoxicillin levels were measured after the first and last antibiotic doses and gut microbiomes were evaluated using whole genome shotgun sequence metagenomics analyses of fecal DNA prior to and after antibiotic treatment. Serum amoxicillin levels did not significantly differ +/- SYN-007 after the first dose for all SYN-007 formulations, while only one SYN-007 formulation did not significantly reduce systemic antibiotic concentrations after the last dose. Gut microbiomes of animals receiving amoxicillin alone displayed significant loss of diversity and emergence of antibiotic resistance genes. In contrast, for animals receiving amoxicillin + SYN-007, microbiome diversities were not altered significantly and the presence of antibiotic resistance genes was reduced. These data demonstrate that SYN-007 diminishes amoxicillin-mediated microbiome disruption and mitigates emergence and propagation of antibiotic resistance genes without interfering with antibiotic systemic absorption. Thus, SYN-007 has the potential to protect the gut microbiome by inactivation of beta-lactam antibiotics when administered by both oral and parenteral routes and to reduce emergence of antibiotic-resistant pathogens.

Metallic nanoparticles induced antibiotic resistance genes attenuation of leachate culturable microbiota: The combined roles of growth inhibition, ion dissolution and oxidative stress

The dissemination and propagation of antibiotic resistance genes (ARGs) is an emerging global health concern, and the potential effects of nanomaterials on ARGs fates have drawn much attention recently. In the current study, the effects of metallic nanoparticles on ARGs occurrence of leachate culturable microbiota were investigated by four typical metal and metal oxide nanoparticles (Cu, Zn, CuO, and ZnO). The ARGs diversity was remarkably decreased during the cultivation and enrichment of leachate microbiota, and their abundances decreased for 1.4–3.2 orders of magnitude. The presence of nanoparticles facilitated the ARGs attenuation, and the magnitude of effects depended on types of nanoparticles and ARGs. Metal oxide nanoparticles caused more remarkable effects than metal nanoparticles. Mechanism analysis indicated that bacterial growth was inhibited, and the dissolved metal ions from nanoparticles partially contributed to nanoparticles decreasing ARGs. Flow cytometry experiments further confirmed that nanoparticles could enter bacterial cells, and then induce excessive reactive oxygen species (ROS) generation and increase membrane permeability. Finally, the possible mechanisms were put forward, and the structural equation models (SEM) differentiated the contribution of different factors shaping ARGs. The dissolved metal ions and growth inhibition caused by nanoparticles decreased ARGs transfer frequencies via exerting excessive metal stress and lowering population density. On the other hand, nanoparticles were incorporated into the cells, and then induced the generation of ROS, which might facilitate ARGs horizontal transfer via increasing membrane permeability, or decrease ARGs via the damage of genomic and plasmid DNA. Therefore, nanoparticles could affect ARGs fates via several ways, and combined effects finally determined the ARGs variations.