Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by plasmids across genera. - Related Documents




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926401.0000Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by plasmids across genera. Antibiotic resistance is a worldwide public health concern. Conjugative transfer between closely related strains or species of bacteria is an important method for the horizontal transfer of multidrug-resistance genes. The extent to which nanomaterials are able to cause an increase in antibiotic resistance by the regulation of the conjugative transfer of antibiotic-resistance genes in bacteria, especially across genera, is still unknown. Here we show that nanomaterials in water can significantly promote the horizontal conjugative transfer of multidrug-resistance genes mediated by the RP4, RK2, and pCF10 plasmids. Nanoalumina can promote the conjugative transfer of the RP4 plasmid from Escherichia coli to Salmonella spp. by up to 200-fold compared with untreated cells. We also explored the mechanisms behind this phenomenon and demonstrate that nanoalumina is able to induce oxidative stress, damage bacterial cell membranes, enhance the expression of mating pair formation genes and DNA transfer and replication genes, and depress the expression of global regulatory genes that regulate the conjugative transfer of RP4. These findings are important in assessing the risk of nanomaterials to the environment, particularly from water and wastewater treatment systems, and in the estimation of the effect of manufacture and use of nanomaterials on the environment.201222411796
939710.9998Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments. Plasmid conjugation is a major route for the spread of antibiotic resistance genes. Inhibiting conjugation has been proposed as a feasible strategy to stop or delay the propagation of antibiotic resistance genes. Several compounds have been shown to be conjugation inhibitors in vitro, specifically targeting the plasmid horizontal transfer machinery. However, the in vivo efficiency and the applicability of these compounds to clinical and environmental settings remained untested. Here we show that the synthetic fatty acid 2-hexadecynoic acid (2-HDA), when used as a fish food supplement, lowers the conjugation frequency of model plasmids up to 10-fold in controlled water microcosms. When added to the food for mice, 2-HDA diminished the conjugation efficiency 50-fold in controlled plasmid transfer assays carried out in the mouse gut. These results demonstrate the in vivo efficiency of conjugation inhibitors, paving the way for their potential application in clinical and environmental settings. IMPORTANCE The spread of antibiotic resistance is considered one of the major threats for global health in the immediate future. A key reason for the speed at which antibiotic resistance spread is the ability of bacteria to share genes with each other. Antibiotic resistance genes harbored in plasmids can be easily transferred to commensal and pathogenic bacteria through a process known as bacterial conjugation. Blocking conjugation is thus a potentially useful strategy to curtail the propagation of antibiotic resistance. Conjugation inhibitors (COINS) are a series of compounds that block conjugation in vitro. Here we show that COINS efficiently block plasmid transmission in two controlled natural environments, water microcosms and the mouse gut. These observations indicate that COIN therapy can be used to prevent the spread of antibiotic resistance.202134425705
677820.9998Bisphenol S Promotes the Transfer of Antibiotic Resistance Genes via Transformation. The antibiotic resistance crisis has seriously jeopardized public health and human safety. As one of the ways of horizontal transfer, transformation enables bacteria to acquire exogenous genes naturally. Bisphenol compounds are now widely used in plastics, food, and beverage packaging, and have become a new environmental pollutant. However, their potential relationship with the spread of antibiotic resistance genes (ARGs) in the environment remains largely unexplored. In this study, we aimed to assess whether the ubiquitous bisphenol S (BPS) could promote the transformation of plasmid-borne ARGs. Using plasmid pUC19 carrying the ampicillin resistance gene as an extracellular ARG and model microorganism E. coli DH5α as the recipient, we established a transformation system. Transformation assays revealed that environmentally relevant concentrations of BPS (0.1-10 μg/mL) markedly enhanced the transformation frequency of plasmid-borne ARGs into E. coli DH5α up to 2.02-fold. Fluorescent probes and transcript-level analyses suggest that BPS stimulated increased reactive oxygen species (ROS) production, activated the SOS response, induced membrane damage, and increased membrane fluidity, which weakened the barrier for plasmid transfer, allowing foreign DNA to be more easily absorbed. Moreover, BPS stimulates ATP supply by activating the tricarboxylic acid (TCA) cycle, which promotes flagellar motility and expands the search for foreign DNA. Overall, these findings provide important insight into the role of bisphenol compounds in facilitating the horizontal spread of ARGs and emphasize the need to monitor the residues of these environmental contaminants.202439337307
676330.9998Sub-lethal photocatalysis promotes horizontal transfer of antibiotic resistance genes by conjugation and transformability. The spread of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in water is increasingly becoming a worldwide problem due to frequent recent major public health events. Herein, the horizontal ARG transfer mechanisms were studied under sub-lethal photocatalysis. The results show that ARGs had at most a 3- to 6-fold increase in the conjugative transfer frequency when only donor bacteria were induced with sub-lethal photocatalysis, while the frequency exhibited a trend toward inhibition when only the recipient bacteria were induced. However, when the donor or recipient bacteria were induced beforehand for a specific time, the frequency increased by a maximum of 10- to 22-fold. Moreover, the horizontal transfer frequency and its mechanism were related to the oxidative stress systems, ATP systems and the expression of related genes. Furthermore, the transformability of extracellular plasmids of the ARB and the contribution in horizontal transfer were also studied. Results show that the transformation frequency accounted for up to 50% of the total number of transconjugants, indicating that transformation might be a primary mode of horizontal ARG transfer by ARB in water. All of the above results demonstrate that sub-lethal photocatalysis will increase the frequency of horizontal gene transfer of ARGs through both conjugative transfer and the transformation pathway, which increases the risk of ARB in aquatic environments.202235841790
926540.9998Conjugation is necessary for a bacterial plasmid to survive under protozoan predation. Horizontal gene transfer by conjugative plasmids plays a critical role in the evolution of antibiotic resistance. Interactions between bacteria and other organisms can affect the persistence and spread of conjugative plasmids. Here we show that protozoan predation increased the persistence and spread of the antibiotic resistance plasmid RP4 in populations of the opportunist bacterial pathogen Serratia marcescens. A conjugation-defective mutant plasmid was unable to survive under predation, suggesting that conjugative transfer is required for plasmid persistence under the realistic condition of predation. These results indicate that multi-trophic interactions can affect the maintenance of conjugative plasmids with implications for bacterial evolution and the spread of antibiotic resistance genes.201626843557
926050.9998The Evolution of Plasmid Transfer Rate in Bacteria and Its Effect on Plasmid Persistence. AbstractPlasmids are extrachromosomal segments of DNA that can transfer genes between bacterial cells. Many plasmid genes benefit bacteria but cause harm to human health by granting antibiotic resistance to pathogens. Transfer rate is a key parameter for predicting plasmid dynamics, but observed rates are highly variable, and the effects of selective forces on their evolution are unclear. We apply evolutionary analysis to plasmid conjugation models to investigate selective pressures affecting plasmid transfer rate, emphasizing host versus plasmid control, the costs of plasmid transfer, and the role of recipient cells. Our analyses show that plasmid-determined transfer rates can be predicted with three parameters (host growth rate, plasmid loss rate, and the cost of plasmid transfer on growth) under some conditions. We also show that low-frequency genetic variation in transfer rate can accumulate, facilitating rapid adaptation to changing conditions. Furthermore, reduced transfer rates due to host control have limited effects on plasmid prevalence until low enough to prevent plasmid persistence. These results provide a framework to predict plasmid transfer rate evolution in different environments and demonstrate the limited impact of host mechanisms to control the costs incurred when plasmids are present.202134559608
925960.9998Static recipient cells as reservoirs of antibiotic resistance during antibiotic therapy. How does taking the full course of antibiotics prevent antibiotic resistant bacteria establishing in patients? We address this question by testing the possibility that horizontal/lateral gene transfer (HGT) is critical for the accumulation of the antibiotic-resistance phenotype while bacteria are under antibiotic stress. Most antibiotics prevent bacterial reproduction, some by preventing de novo gene expression. Nevertheless, in some cases and at some concentrations, the effects of most antibiotics on gene expression may not be irreversible. If the stress is removed before the bacteria are cleared from the patients by normal turnover, gene expression restarts, converting the residual population to phenotypic resistance. Using mathematical models we investigate how static recipients of resistance genes carried by plasmids accumulate resistance genes, and how specifically an environment cycling between presence and absence of the antibiotic uniquely favors the evolution of horizontally mobile resistance genes. We found that the presence of static recipients can substantially increase the persistence of the plasmid and that this effect is most pronounced when the cost of carriage of the plasmid decreases the cell's growth rate by as much as a half or more. In addition, plasmid persistence can be enhanced even when conjugation rates are as low as half the rate required for the plasmid to persist as a parasite on its own.200616723146
860570.9998Exposure to bisphenol compounds accelerates the conjugative transfer of antibiotic resistance plasmid. Antimicrobial resistance poses the most formidable challenge to public health, with plasmid-mediated horizontal gene transfer playing a pivotal role in its global spread. Bisphenol compounds (BPs), a group of environmental contaminants with endocrine-disrupting properties, are extensively used in various plastic products and can be transmitted to food. However, the impact of BPs on the plasmid-mediated horizontal transfer of antibiotic resistance genes (ARGs) has not yet been elucidated. Herein, we demonstrate that BPs could promote the conjugative transfer frequency of RP4-7 and clinically multidrug-resistant plasmids. Furthermore, the promoting effect of BPs on the plasmid transfer was also confirmed in a murine model. Microbial diversity analysis of transconjugants indicated an increase in α diversity in the BPAF-treated group, along with the declined richness of some beneficial bacteria and elevated richness of Faecalibaculum rodentium, which might serve as an intermediate repository for resistance plasmids. The underlying mechanisms driving the enhanced conjugative transfer upon BPAF treatment include exacerbated oxidative stress, disrupted membrane homeostasis, augmented energy metabolism, and the increased expression of conjugation-related genes. Collectively, our findings highlight the potential risk associated with the exacerbated dissemination of AMR both in vitro and in vivo caused by BPs exposure.202439278585
379880.9998Genome-Wide Association Study Reveals Host Factors Affecting Conjugation in Escherichia coli. The emergence and dissemination of antibiotic resistance threaten the treatment of common bacterial infections. Resistance genes are often encoded on conjugative elements, which can be horizontally transferred to diverse bacteria. In order to delay conjugative transfer of resistance genes, more information is needed on the genetic determinants promoting conjugation. Here, we focus on which bacterial host factors in the donor assist transfer of conjugative plasmids. We introduced the broad-host-range plasmid pKJK10 into a diverse collection of 113 Escherichia coli strains and measured by flow cytometry how effectively each strain transfers its plasmid to a fixed E. coli recipient. Differences in conjugation efficiency of up to 2.7 and 3.8 orders of magnitude were observed after mating for 24 h and 48 h, respectively. These differences were linked to the underlying donor strain genetic variants in genome-wide association studies, thereby identifying candidate genes involved in conjugation. We confirmed the role of fliF, fliK, kefB and ucpA in the donor ability of conjugative elements by validating defects in the conjugation efficiency of the corresponding lab strain single-gene deletion mutants. Based on the known cellular functions of these genes, we suggest that the motility and the energy supply, the intracellular pH or salinity of the donor affect the efficiency of plasmid transfer. Overall, this work advances the search for targets for the development of conjugation inhibitors, which can be administered alongside antibiotics to more effectively treat bacterial infections.202235336183
677490.9998Both silver ions and silver nanoparticles facilitate the horizontal transfer of plasmid-mediated antibiotic resistance genes. Antibiotic resistance in bacteria is a growing threat to global human health. Horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs) is recognized as the primary contributor to antibiotic resistance dissemination. Silver nanoparticles (AgNPs) are widely used in personal care products as antimicrobial agents. While heavy metals are known to induce antibiotic resistance in bacteria, it is not known whether AgNPs in the environment can stimulate the HGT of ARGs. Here, we report that both AgNPs and ionic silver Ag(+), at environmentally relevant and sub-lethal concentrations, facilitate the conjugative transfer of plasmid-borne ARGs across bacterial genera (from the donor Escherichia coli K-12 LE392 to the recipient Pseudomonas putida KT2440). The underlying mechanisms of the Ag(+)- or AgNPs-promoted HGT were unveiled by detecting oxidative stress and cell membrane permeability, combined with genome-wide RNA sequencing and proteomic analyses. It was found that both Ag(+) and AgNPs exposure induced various bacterial responses that included reactive oxygen species (ROS) generation, membrane damage and the SOS response. This study exposes the potential ecological risks of environmental levels of AgNPs and Ag(+) for promoting the spread of ARGs and highlights concerns regarding the management of nanoparticles and heavy metals.202031783256
3795100.9998Gene transfer between Salmonella enterica serovar Typhimurium inside epithelial cells. Virulence and antibiotic resistance genes transfer between bacteria by bacterial conjugation. Conjugation also mediates gene transfer from bacteria to eukaryotic organisms, including yeast and human cells. Predicting when and where genes transfer by conjugation could enhance our understanding of the risks involved in the release of genetically modified organisms, including those being developed for use as vaccines. We report here that Salmonella enterica serovar Typhimurium conjugated inside cultured human cells. The DNA transfer from donor to recipient bacteria was proportional to the probability that the two types of bacteria occupied the same cell, which was dependent on viable and invasive bacteria and on plasmid tra genes. Based on the high frequencies of gene transfer between bacteria inside human cells, we suggest that such gene transfers occur in situ. The implications of gene transfer between bacteria inside human cells, particularly in the context of antibiotic resistance, are discussed.200211914355
3797110.9997Human intestinal cells modulate conjugational transfer of multidrug resistance plasmids between clinical Escherichia coli isolates. Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems to study this process. We established an in vitro co-culture system to study the interaction between human intestinal cells and bacteria. We show that the conjugation efficiency of a plasmid encoding an extended spectrum beta-lactamase is reduced when clinical isolates of Escherichia coli are co-cultured with human intestinal cells. We show that filtered media from co-cultures contain a factor that reduces conjugation efficiency. Protease treatment of the filtered media eliminates this inhibition of conjugation. This data suggests that a peptide or protein based factor is secreted on the apical side of the intestinal cells exposed to bacteria leading to a two-fold reduction in conjugation efficiency. These results show that human gut epithelial cells can modulate bacterial conjugation and may have relevance to gene exchange in the gut.201424955767
6772120.9997Disinfectants facilitate the transformation of exogenous antibiotic resistance genes via multiple pathways. The prevalence and spread of multidrug-resistant (MDR) bacteria pose a global challenge to public health. Natural transformation is one of the essential ways for horizontal transfer of antibiotic resistance genes (ARGs). Although disinfectants are frequently used during COVID-19, little is known about whether these disinfectants are associated with the transformation of plasmid-borne ARGs. In our study, we assessed the effect of some disinfectants on bacterial transformation using resistance plasmids as extracellular DNA and E. coli DH5α as the recipient bacteria. The results showed that these disinfectants at environmentally relevant concentrations, including benzalkonium bromide (BB), benzalkonium chloride (BC) and polyhexamethylene guanidine hydrochloride (PHMG), significantly enhanced the transformation of plasmid-encoded ARGs. Furthermore, we investigated the mechanisms underlying the promotive effect of disinfectants on transformation. We revealed that the addition of disinfectants significantly increased the membrane permeability and promoted membrane-related genes expression. Moreover, disinfectants led to the boosted bacterial respiration, ATP production and flagellum motility, as well as increased expression of bacterial secretion system-related genes. Together, our findings shed insights into the spread of ARGs through bacterial transformation and indicate potential risks associated with the widespread use of disinfectants.202336857920
9262130.9997Effect of chemotherapeutic agents on natural transformation frequency in Acinetobacter baylyi. Natural transformation is the ability of a bacterial cell to take up extracellular DNA which is subsequently available for recombination into the chromosome (or maintenance as an extrachromosomal element). Like other mechanisms of horizontal gene transfer, natural transformation is a significant driver for the dissemination of antimicrobial resistance. Recent studies have shown that many pharmaceutical compounds such as antidepressants and anti-inflammatory drugs can upregulate transformation frequency in the model species Acinetobacter baylyi. Chemotherapeutic compounds have been shown to increase the abundance of antimicrobial resistance genes and increase colonization rates of potentially pathogenic bacteria in patient gastrointestinal tracts, indicating an increased risk of infection and providing a pool of pathogenicity or resistance genes for transformable commensal bacteria. We here test for the effect of six cancer chemotherapeutic compounds on A. baylyi natural transformation frequency, finding two compounds, docetaxel and daunorubicin, to significantly decrease transformation frequency, and daunorubicin to also decrease growth rate significantly. Enhancing our understanding of the effect of chemotherapeutic compounds on the frequency of natural transformation could aid in preventing the horizontal spread of antimicrobial resistance genes.202439135654
6776140.9997Natural 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.202031999971
9270150.9997Activation of class 1 integron integrase is promoted in the intestinal environment. Class 1 integrons are widespread genetic elements playing a major role in the dissemination of antibiotic resistance. They allow bacteria to capture, express and exchange antibiotic resistance genes embedded within gene cassettes. Acquisition of gene cassettes is catalysed by the class 1 integron integrase, a site-specific recombinase playing a key role in the integron system. In in vitro planktonic culture, expression of intI1 is controlled by the SOS response, a regulatory network which mediates the repair of DNA damage caused by a wide range of bacterial stress, including antibiotics. However, in vitro experimental conditions are far from the real lifestyle of bacteria in natural environments such as the intestinal tract which is known to be a reservoir of integrons. In this study, we developed an in vivo model of intestinal colonization in gnotobiotic mice and used a recombination assay and quantitative real-time PCR, to investigate the induction of the SOS response and expression and activity of the class 1 integron integrase, IntI1. We found that the basal activity of IntI1 was higher in vivo than in vitro. In addition, we demonstrated that administration of a subinhibitory concentration of ciprofloxacin rapidly induced both the SOS response and intI1 expression that was correlated with an increase of the activity of IntI1. Our findings show that the gut is an environment in which the class 1 integron integrase is induced and active, and they highlight the potential role of integrons in the acquisition and/or expression of resistance genes in the gut, particularly during antibiotic therapy.202235482826
3814160.9997Plasmids spread very fast in heterogeneous bacterial communities. Conjugative plasmids can mediate gene transfer between bacterial taxa in diverse environments. The ability to donate the F-type conjugative plasmid R1 greatly varies among enteric bacteria due to the interaction of the system that represses sex-pili formations (products of finOP) of plasmids already harbored by a bacterial strain with those of the R1 plasmid. The presence of efficient donors in heterogeneous bacterial populations can accelerate plasmid transfer and can spread by several orders of magnitude. Such donors allow millions of other bacteria to acquire the plasmid in a matter of days whereas, in the absence of such strains, plasmid dissemination would take years. This "amplification effect" could have an impact on the evolution of bacterial pathogens that exist in heterogeneous bacterial communities because conjugative plasmids can carry virulence or antibiotic-resistance genes.200212524329
3804170.9997Non-invasive determination of conjugative transfer of plasmids bearing antibiotic-resistance genes in biofilm-bound bacteria: effects of substrate loading and antibiotic selection. Biofilms cause much of all human microbial infections. Attempts to eradicate biofilm-based infections rely on disinfectants and antibiotics. Unfortunately, biofilm bacteria are significantly less responsive to antibiotic stressors than their planktonic counterparts. Sublethal doses of antibiotics can actually enhance biofilm formation. Here, we have developed a non-invasive microscopic image analyses to quantify plasmid conjugation within a developing biofilm. Corroborating destructive samples were analyzed by a cultivation-independent flow cytometry analysis and a selective plate count method to cultivate transconjugants. Increases in substrate loading altered biofilm 3-D architecture and subsequently affected the frequency of plasmid conjugation (decreases at least two times) in the absence of any antibiotic selective pressure. More importantly, donor populations in biofilms exposed to a sublethal dose of kanamycin exhibited enhanced transfer efficiency of plasmids containing the kanamycin resistance gene, up to tenfold. However, when stressed with a different antibiotic, imipenem, transfer of plasmids containing the kan(R+) gene was not enhanced. These preliminary results suggest biofilm bacteria "sense" antibiotics to which they are resistant, which enhances the spread of that resistance. Confocal scanning microscopy coupled with our non-invasive image analysis was able to estimate plasmid conjugative transfer efficiency either averaged over the entire biofilm landscape or locally with individual biofilm clusters.201322669634
8982180.9997Ampicillin Exposure and Glutathione Deficiency Synergistically Promote Conjugative Transfer of Plasmid-Borne Antibiotic Resistance Genes. Plasmid-mediated conjugation is an important pathway for the spread of antibiotic resistance genes (ARGs), posing a significant risk to global public health. It has been reported that the conjugative transfer of ARGs could be enhanced by oxidative stress. Whether endogenous glutathione (GSH), a major non-protein thiol compound involved in cellular redox homeostasis, influences conjugative transfer is unknown. In this study, we show that the deletion of the GSH biosynthesis gene gshA and ampicillin exposure synergistically promoted the conjugative transfer of plasmid RP4 bearing multiple ARGs from the soil bacterium Enterobacter sp. CZ-1 to Escherichia coli S17-1λπ in co-culture experiments and to diverse soil bacteria belonging to eight phyla, including some potential human pathogens, in a soil incubation experiment. The deletion of gshA increased ROS generation and cell membrane permeability, and upregulated the expression of the genes involved in intracellular oxidative stress regulation, membrane permeability, plasmid replication, and the SOS response process, especially under ampicillin exposure. These results suggest that endogenous GSH is an important factor affecting the spread of plasmid-borne ARGs. Exposure to antibiotics and environmental stresses that cause a depletion of endogenous GSH in vivo are likely to increase the risk of ARG dissemination in the environment.202540346915
6775190.9997Copper nanoparticles and copper ions promote horizontal transfer of plasmid-mediated multi-antibiotic resistance genes across bacterial genera. The spread of antibiotic resistance has become a major concern for public health. As emerging contaminants, various metallic nanoparticles (NPs) and ionic heavy metals have been ubiquitously detected in various environments. Although previous studies have indicated NPs and ionic heavy metals could exhibit co-selection effects for antibiotic resistance, little is known about whether and how they could promote antibiotic resistance spread via horizontal gene transfer across bacterial genera. This study, we report both CuO NPs and copper ions (Cu(2+)) could stimulate the conjugative transfer of multiple-drug resistance genes. When exposing bacteria to CuO NPs or Cu(2+) at environmental-relevant and sub-inhibitory concentrations (e.g., 1-100 μmol/L), conjugation frequencies of plasmid-encoded antibiotic resistance genes across genera (i.e., from Escherichia coli to Pseudomonas putida) were significantly enhanced (p < 0.05). The over-production of reactive oxygen species played a crucial role in promoting conjugative transfer. Genome-wide RNA and protein sequencing suggested expressional levels of genes and proteins related to oxidative stress, cell membrane permeability, and pilus generation were significantly up-regulated under CuO NPs and Cu(2+) exposure (p < 0.05). This study provides insights in the contributions of NPs and heavy metals on the spread of antibiotic resistance.201931158594