Nitrogen-Doped Carbon Dots Facilitate CRISPR/Cas for Reducing Antibiotic Resistance Genes in the Environment. - Related Documents




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974001.0000Nitrogen-Doped Carbon Dots Facilitate CRISPR/Cas for Reducing Antibiotic Resistance Genes in the Environment. The continued acquisition and propagation of antibiotic resistance genes (ARGs) in the environment confound efforts to manage the global rise in antibiotic resistance. Here, CRISPR-Cas9/sgRNAs carried by nitrogen-doped carbon dots (NCDs) were developed to precisely target multi-"high-risk" ARGs (tet, cat, and aph(3')-Ia) commonly detected in the environment. NCDs facilitated the delivery of Cas9/sgRNAs to Escherichia coli (E. coli) without cytotoxicity, achieving sustained elimination of target ARGs. The elimination was optimized using different weight ratios of NCDs and Cas9 protein (1:1, 1:20, and 1:40), and Cas9/multi sgRNAs were designed to achieve multi-cleavage of ARGs in either a single strain or mixed populations. Importantly, NCDs successfully facilitated Cas9/multi sgRNAs for resensitization of antibiotic-resistant bacteria in soil (approaching 50%), whereas Cas9/multi sgRNAs alone were inactivated in the complex environment. This work highlights the potential of a fast and precise strategy to minimize the reservoir of antibiotic resistance in agricultural system.202438335532
334910.9995Phenotypic Tracking of Antibiotic Resistance Spread via Transformation from Environment to Clinic by Reverse D(2)O Single-Cell Raman Probing. The rapid spread of antibiotic resistance threatens our fight against bacterial infections. Environments are an abundant reservoir of potentially transferable resistance to pathogens. However, the trajectory of antibiotic resistance genes (ARGs) spreading from environment to clinic and the associated risk remain poorly understood. Here, single-cell Raman spectroscopy combined with reverse D(2)O labeling (Raman-rD(2)O) was developed as a sensitive and rapid phenotypic tool to track the spread of plasmid-borne ARGs from soil to clinical bacteria via transformation. Based on the activity of bacteria in assimilating H to substitute prelabeled D under antibiotic treatment, Raman-rD(2)O sensitively discerned a small minority of phenotypically resistant transformants from a large pool of recipient cells. Its single-cell level detection greatly facilitated the direct calculation of spread efficiency. Raman-rD(2)O was further employed to study the transfer of complex soil resistant plasmids to pathogenic bacteria. Soil plasmid ARG-dependent transformability against five clinically relevant antibiotics was revealed and used to assess the spreading risk of different soil ARGs, i.e., ampicillin > cefradine and ciprofloxacin > meropenem and vancomycin. The developed single-cell phenotypic method can track the fate and risk of environmental ARGs to pathogenic bacteria and may guide developing new strategies to prevent the spread of high-risk ARGs.202033169970
850220.9994Simultaneously disinfection of amoebae, endosymbiotic bacteria, and resistance genes using a novel two-electron water oxidation strategy. Amoebae, which serve as important vectors for various pathogenic bacteria, are ubiquitous in natural and artificial water systems. Their robust survival capabilities and protective characteristics render conventional disinfection methods largely ineffective. Moreover, amoeba cells provide an ideal environment for the replication and transfer of antibiotic resistance genes, posing a significant threat to human health and safety. In this study, an in-situ activation system for electrocatalytic water oxidation was developed. This system effectively inactivates amoeba spores and their intracellular symbiotic bacteria while simultaneously reducing the abundance of resistance genes through the generation of hydroxyl radicals (•OH) and carbonate free radicals (•CO(3)(-)). The results demonstrated a 99.9 % inactivation rate for amoeba spores and a 99.999 % inactivation rate for intracellular bacteria. In addition, the prevalence of resistant genes in bacteria within amoebae, specifically including sul1 (sulfonamide resistance), tetA (tetracycline resistance), blaFOX (cefoxitin resistance), arsB (arsenic resistance), czcA (cadmium resistance), and copA (copper resistance), was significantly reduced by approximately 16 %-62.6 %. Therefore, this study introduces a new technology capable of simultaneously treating amoeba spores, intracellular bacteria, and resistance genes, which holds significant importance for reducing the spread of resistant genes and enhancing public health safety.202540449332
973930.9993Au-Fe(3)O(4) nanozyme coupled with CRISPR-Cas12a for sensitive and visual antibiotic resistance diagnosing. The accumulation and spread of antibiotic resistance bacteria (ARB) in the environment may accelerate the formation of superbugs and seriously threaten the health of all living beings. The timeliness and accurate diagnosing of antibiotic resistance is essential to controlling the propagation of superbugs in the environment and formulating effective public health management programs. Herein, we developed a speedy, sensitive, accurate, and user-friendly colorimetric assay for antibiotic resistance, via a synergistic combination of the peroxidase-like property of the Au-Fe(3)O(4) nanozyme and the specific gene identification capability of the CRISPR-Cas12a. Once the CRISPR-Cas12a system recognizes a target resistance gene, it activates its trans-cleavage activity and subsequently releases the Au-Fe(3)O(4) nanozymes, which oxidizes the 3,3,5,5-tetramethylbenzidine (TMB) with color change from transparent to blue. The diagnosing signals could be captured and analyzed by a smartphone. This method detected kanamycin-resistance genes, ampicillin-resistance genes, and chloramphenicol-resistance genes by simple operation steps with high sensitivity (<0.1 CFU μL(-1)) and speediness (<1 h). This approach may prove easy for the accurate and sensitive diagnosis of the ARGs or ARB in the field, thus surveilling and controlling the microbial water quality flexibly and efficiently.202336925313
973840.9993Detection and Quantification of Antimicrobial-Resistant Cells in Aquatic Environments by Bioorthogonal Noncanonical Amino Acid Tagging. Aquatic environments are important reservoirs of antibiotic wastes, antibiotic resistance genes, and bacteria, enabling the persistence and proliferation of antibiotic resistance in different bacterial populations. To prevent the spread of antibiotic resistance, effective approaches to detect antimicrobial susceptibility in aquatic environments are highly desired. In this work, we adopt a metabolism-based bioorthogonal noncanonical amino acid tagging (BONCAT) method to detect, visualize, and quantify active antimicrobial-resistant bacteria in water samples by exploiting the differences in bacterial metabolic responses to antibiotics. The BONCAT approach can be applied to rapidly detect bacterial resistance to multiple antibiotics within 20 min of incubation, regardless of whether they act on proteins or DNA. In addition, the combination of BONCAT with the microscope enables the intuitive characterization of antibiotic-resistant bacteria in mixed systems at single-cell resolution. Furthermore, BONCAT coupled with flow cytometry exhibits good performance in determining bacterial resistance ratios to chloramphenicol and population heterogeneity in hospital wastewater samples. In addition, this approach is also effective in detecting antibiotic-resistant bacteria in natural water samples. Therefore, such a simple, fast, and efficient BONCAT-based approach will be valuable in monitoring the increase and spread of antibiotic resistance within natural and engineered aquatic environments.202236251006
781350.9992A framework predicting removal efficacy of antibiotic resistance genes during disinfection processes with machine learning. Disinfection has been applied widely for the removal of antibiotic resistance genes (ARGs) to curb the spread of antibiotic resistance. Quantitative polymerase chain reaction (qPCR) is the most used method to quantify the damage of DNA thus calculating the ARG degradation during disinfection but suffers the deviation due to the limitation of amplicon length. In contrast, transformation assay more accurately measures ARG deactivation based on expression of disinfected ARG in the receiving bacteria but is typically laborious and material-intensive. This work applied machine learning (ML) to develop a framework by using qPCR results as a proxy to estimate the transformation assay measurements during disinfection with chlorine (FAC), ultraviolet (UV(254)), ozone (O(3)), and hydrogen peroxide/ultraviolet (UV/H(2)O(2)) for multiple kinds of ARGs. ARG degradation rates and deactivation rates were well predicted with the optimal correlation coefficient (R(2)) of all test sets > 0.926 and > 0.871, respectively. Besides, by concatenating the ARG degradation and deactivation predictive models, ARG removal efficiency under given disinfection conditions was directly predicted as the loss of transformation activity with R(2) > 0.828. Furthermore, an online platform was built to provide users with access to the developed ML models for rapid and accurate evaluation of ARG removal efficiency.202540179779
760260.9992A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes. Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG) in the aquatic environment have become an emerging contaminant issue, which has implications for human and ecological health. This review begins with an introduction to the occurrence of ARB and ARG in different environmental systems such as natural environments and drinking water resources. For example, ARG or ARB with resistance to ciprofloxacin, sulfamethoxazole, trimethoprim, quinolone, vancomycin, or tetracycline (e.g., tet(A), tet(B), tet(C), tet(G), tet(O), tet(M), tet(W), sul I, and sul II) have been detected in the environment. The development of resistance may be intrinsic, may be acquired through spontaneous mutations (de novo), or may occur due to horizontal gene transfer from donor bacteria, phages, or free DNA to recipient bacteria. An overview is also provided of the current knowledge regarding inactivation of ARB and ARG, and the mechanism of the effects of different disinfection processes in water and wastewater (chlorination, UV irradiation, Fenton reaction, ozonation, and photocatalytic oxidation). The effects of constructed wetlands and nanotechnology on ARB and ARG are also summarized.201626775188
939770.9992Conjugation 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
850180.9992Mechanistic insight of simultaneous removal of tetracycline and its related antibiotic resistance bacteria and genes by ferrate(VI). The emergence of antibiotics and their corresponding antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) have posed great challenges to the public health. The paper demonstrates the removal of co-existing tetracycline (TC), its resistant Escherichia coli (E. coli), and ARGs (tetA and tetR) in a mixed system by applying ferrate(VI) (Fe(VI)O(4)(2-), Fe(VI)) at pH 7.0. TC was efficiently degraded by Fe(VI), and the rapid inactivation of the resistant E. coli was found with the complete loss of culturability. The results of flow cytometry suggested that the damage of membrane integrity and respiratory activity were highly correlated with the Fe(VI) dosages. Moreover, high-dose Fe(VI) eliminates 6 log(10) viable but non-culturable (VBNC) cells and even breaks the cells into fragments. ARGs in extracellular form (e-ARGs) exhibited a high sensitivity of 4.44 log(10) removal to Fe(VI). Comparatively, no removal of intracellular ARGs (i-ARGs) was observed due to the multi-protection of cellular structure and rapid decay of Fe(VI). The oxidized products of TC were assessed to be less toxic than the parent compound. Overall, this study demonstrated the superior efficiency and great promise of Fe(VI) on simultaneous removal of antibiotics and their related ARB and ARGs in water.202133984704
738490.9992Uncovering antimicrobial resistance in three agricultural biogas plants using plant-based substrates. Antimicrobial resistance (AMR) is becoming an increasing global concern and the anaerobic digestion (AD) process represents a potential transmission route when digestates are used as fertilizing agents. AMR contaminants, e.g. antibiotic-resistant bacteria (ARB) and plasmid-mediated antibiotic resistance genes (ARGs) have been found in different substrates and AD systems, but not yet been investigated in plant-based substrates. AMR transfer from soils to vegetable microbiomes has been observed, and thus crop material potentially represents a so far neglected AMR load in agricultural AD processes, contributing to AMR spread. In order to test this hypothesis, this study examined the AMR situation throughout the process of three biogas plants using plant-based substrates only, or a mixture of plant-based and manure substrates. The evaluation included a combination of culture-independent and -dependent methods, i.e., identification of ARGs, plasmids, and pathogenic bacteria by DNA arrays, and phylogenetic classification of bacterial isolates and their phenotypic resistance pattern. To our knowledge, this is the first study on AMR in plant-based substrates and the corresponding biogas plant. The results showed that the bacterial community isolated from the investigated substrates and the AD processing facilities were mainly Gram-positive Bacillus spp. Apart from Pantoea agglomerans, no other Gram-negative species were found, either by bacteria culturing or by DNA typing array. In contrast, the presence of ARGs and plasmids clearly indicated the existence of Gram-negative pathogenic bacteria, in both substrate and AD process. Compared with substrates, digestates had lower levels of ARGs, plasmids, and culturable ARB. Thus, digestate could pose a lower risk of spreading AMR than substrates per se. In conclusion, plant-based substrates are associated with AMR, including culturable Gram-positive ARB and Gram-negative pathogenic bacteria-associated ARGs and plasmids. Thus, the AMR load from plant-based substrates should be taken into consideration in agricultural biogas processing.202235306061
7520100.9992Antibiotic Resistance Gene-Carrying Plasmid Spreads into the Plant Endophytic Bacteria using Soil Bacteria as Carriers. Applications of animal manure and treated wastewater could enrich antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the plant microbiome. However, the mechanistic studies of the transmission of ARB and ARGs from the environment to plant endophytic bacteria were few. Herein, a genetically engineered fluorescent Escherichia coli harboring a conjugative RP4 plasmid that carries three ARGs was used to trace its spread into Arabidopsis thaliana interior in a tetracycline-amended hydroponic system in the absence or presence of a simulated soil bacterial community. Confocal microscope observation demonstrated that E. coli was internalized into plant tissues and the carried RP4 plasmid was transferred into plant endophytic bacteria. More importantly, we observed that soil bacteria inhibited the internalization of E. coli but substantially promoted RP4 plasmid spread into the plant microbiome. The altered RP4-carrying bacterial community composition in the plant microbiome and the increased core-shared RP4-carrying bacteria number between plant interior and exterior in the presence of soil bacteria collectively confirmed that soil bacteria, especially Proteobacteria, might capture RP4 from E. coli and then translocate into plant microbiome, resulting in the increased RP4 plasmid spread in the plant endophytes. Overall, our findings provided important insights into the dissemination of ARB and ARGs from the environment to the plant microbiome.202134114802
6490110.9992Recent Trends and Advances of Co(3)O(4) Nanoparticles in Environmental Remediation of Bacteria in Wastewater. Antibiotic resistance is a formidable global threat. Wastewater is a contributing factor to the prevalence of antibiotic-resistant bacteria and genes in the environment. There is increased interest evident from research trends in exploring nanoparticles for the remediation of antibiotic-resistant bacteria. Cobalt oxide (Co(3)O(4)) nanoparticles have various technological, biomedical, and environmental applications. Beyond the environmental remediation applications of degradation or adsorption of dyes and organic pollutants, there is emerging research interest in the environmental remediation potential of Co(3)O(4) nanoparticles and its nanocomposites on antibiotic-resistant and/or pathogenic bacteria. This review focuses on the recent trends and advances in remediation using Co(3)O(4) nanoparticles and its nanocomposites on antibiotic-resistant or pathogenic bacteria from wastewater. Additionally, challenges and future directions that need to be addressed are discussed.202235407254
8500120.9992Plasma induced efficient removal of antibiotic-resistant Escherichia coli and antibiotic resistance genes, and inhibition of gene transfer by conjugation. Antibiotic-resistant bacteria (ARB) and their resistance genes (ARGs) are emerging environmental pollutants that pose great threats to human health. In this study, a novel strategy using plasma was developed to simultaneously remove antibiotic-resistant Escherichia coli (AR bio-56954 E. coli) and its ARGs, aiming to inhibit gene transfer by conjugation. Approximately 6.6 log AR bio-56954 E. coli was inactivated within 10 min plasma treatment, and the antibiotic resistance to tested antibiotics (tetracycline, gentamicin, and amoxicillin) significantly decreased. Reactive oxygen and nitrogen species (RONS) including •OH, (1)O(2), O(2)•(-), NO(2)(-), and NO(3)(-) contributed to ARB and ARGs elimination; their attacks led to destruction of cell membrane, accumulation of excessive intracellular reactive oxygen substances, deterioration of conformational structures of proteins, and destroy of nucleotide bases of DNA. As a result, the ARGs (tet(C), tet(W), blaTEM-1, aac(3)-II), and integron gene intI1), and conjugative transfer frequency of ARGs significantly decreased after plasma treatment. The results demonstrated that plasma has great prospective application in removing ARB and ARGs in water, inhibiting gene transfer by conjugation.202134214852
3985130.9992The scourge of antibiotic resistance: the important role of the environment. Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, β-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.201323723195
6541140.9992Quantitative microbiological risk assessment of complex microbial community in Prawn farm wastewater and applicability of nanoparticles and probiotics for eliminating of antibiotic-resistant bacteria. The current review highlighted the quantitative microbiological risk assessment of Vibrio parahaemolyticus in Prawn farm wastewaters (PFWWs) and the applicability of nanoparticles for eliminating antibiotic-resistant bacteria (ARB). The high availability of the antibiotics in the environment and their transmission into human through the food-chain might cause unknown health effects. The aquaculture environments are considered as a reservoir for the antibiotic resistance genes (ARGs) and contributed effectively in the increasing of ABR. The metagenomic analysis is used to explore ARGs in the non-clinical environment. V. parahaemolyticus is among the pathogenic bacteria which are transmitted through sea food causing human acute gastroenteritis due to available thermostable direct hemolysin (tdh), adhesins, TDH related hemolysin (trh). The inactivation of pathogenic bacteria using nanoparticles act by disturbing the cell membrane, interrupting the transport system, DNA and mitochondria damage, and oxidizing the cellular component by reactive oxygen species (ROS). The chloramphenicol, nitrofurans, and nitroimidazole are among the prohibited drugs in fish and fishery product. The utilization of probiotics is the most effective and safe alternative for antibiotics in Prawn aquaculture. This review will ensure public understanding among the readers on how they can decrease the risk of the antimicrobial resistance distribution in the environment.202134171673
6494150.9992Performance Efficiency of Conventional Treatment Plants and Constructed Wetlands towards Reduction of Antibiotic Resistance. Domestic and industrial wastewater discharges harbor rich bacterial communities, including both pathogenic and commensal organisms that are antibiotic-resistant (AR). AR pathogens pose a potential threat to human and animal health. In wastewater treatment plants (WWTP), bacteria encounter environments suitable for horizontal gene transfer, providing an opportunity for bacterial cells to acquire new antibiotic-resistant genes. With many entry points to environmental components, especially water and soil, WWTPs are considered a critical control point for antibiotic resistance. The primary and secondary units of conventional WWTPs are not designed for the reduction of resistant microbes. Constructed wetlands (CWs) are viable wastewater treatment options with the potential for mitigating AR bacteria, their genes, pathogens, and general pollutants. Encouraging performance for the removal of AR (2-4 logs) has highlighted the applicability of CW on fields. Their low cost of construction, operation and maintenance makes them well suited for applications across the globe, especially in developing and low-income countries. The present review highlights a better understanding of the performance efficiency of conventional treatment plants and CWs for the elimination/reduction of AR from wastewater. They are viable alternatives that can be used for secondary/tertiary treatment or effluent polishing in combination with WWTP or in a decentralized manner.202235052991
4099160.9992In situ, in vivo, and in vitro approaches for studying AMR plasmid conjugation in the gut microbiome. Antimicrobial resistance (AMR) is a global threat, with evolution and spread of resistance to frontline antibiotics outpacing the development of novel treatments. The spread of AMR is perpetuated by transfer of antimicrobial resistance genes (ARGs) between bacteria, notably those encoded by conjugative plasmids. The human gut microbiome is a known 'melting pot' for plasmid conjugation, with ARG transfer in this environment widely documented. There is a need to better understand the factors affecting the incidence of these transfer events, and to investigate methods of potentially counteracting the spread of ARGs. This review describes the use and potential of three approaches to studying conjugation in the human gut: observation of in situ events in hospitalized patients, modelling of the microbiome in vivo predominantly in rodent models, and the use of in vitro models of various complexities. Each has brought unique insights to our understanding of conjugation in the gut. The use and development of these systems, and combinations thereof, will be pivotal in better understanding the significance, prevalence, and manipulability of horizontal gene transfer in the gut microbiome.202336341518
6540170.9992Antibiotic production by soil bacteria under aerobic and micro-oxic conditions. Antimicrobial resistance presents a significant global challenge, undermining the effectiveness of antibiotic therapies and complicating disease management. The origin and spread of antibiotic-resistance genes outpaces the antibiotic discovery process, highlighting an urgent need for new approaches. This study investigated the production of antibiotics by soil bacteria under aerobic and micro-oxic conditions as part of a course-based research experience designed to introduce undergraduates to the global antibiotic resistance crisis. Significant differences in the diameters of the zones of inhibition against three tester strains were observed under differing oxygen concentrations. Soil isolates were identified with 16S rRNA sequence analysis.202539958909
8952180.9992Correlation between the development of phage resistance and the original antibiotic resistance of host bacteria under the co-exposure of antibiotic and bacteriophage. Bacteriophages (phages) are viruses capable of regulating the proliferation of antibiotic resistant bacteria (ARB). However, phages that directly cause host lethality may quickly select for phage resistant bacteria, and the co-evolutionary trade-offs under varying environmental conditions, including the presence of antibiotics, remains unclear as to their impact on phage and antibiotic resistance. Here, we report the emergence of phage resistance in three distinct E. coli strains with varying resistance to β-lactam antibiotics, treated with different ampicillin (AMP) concentrations. Hosts exhibiting stronger antibiotic resistance demonstrated a higher propensity to develop and maintain stable phage resistance. When exposed to polyvalent phage KNT-1, the growth of AMP-sensitive E. coli K12 was nearly suppressed within 18 h, while the exponential growth of AMP-resistant E. coli TEM and super-resistant E. coli NDM-1 was delayed by 12 h and 8 h, respectively. The mutation frequency and mutated colony count of E. coli NDM-1 were almost unaffected by co-existing AMP, whereas for E. coli TEM and K12, these metrics significantly decreased with increasing AMP concentration from 8 to 50 μg/mL, becoming unquantifiable at 100 μg/mL. Furthermore, the fitness costs of phage resistance mutation and its impact on initial antibiotic resistance in bacteria were further examined, through analyzing AMP susceptibility, biofilm formation and EPS secretion of the isolated phage resistant mutants. The results indicated that acquiring phage resistance could decrease antibiotic resistance, particularly for hosts lacking strong antibiotic resistance. The ability of mutants to form biofilm contributes to antibiotic resistance, but the correlation is not entirely positive, while the secretion of extracellular polymeric substance (EPS), especially the protein content, plays a crucial role in protecting the bacteria from both antibiotic and phage exposure. This study explores phage resistance development in hosts with different antibiotic resistance and helps to understand the limitations and possible solutions of phage-based technologies.202438631474
4108190.9992Evaluating targets for control of plasmid-mediated antimicrobial resistance in enteric commensals of beef cattle: a modelling approach. Enteric commensal bacteria of food animals may serve as a reservoir of genes encoding antimicrobial resistance (AMR). The genes are often plasmidic. Different aspects of bacterial ecology can be targeted by interventions to control plasmid-mediated AMR. The field efficacy of interventions remains unclear. We developed a deterministic mathematical model of commensal Escherichia coli in its animate and non-animate habitats within a beef feedlot's pen, with some E. coli having plasmid-mediated resistance to the cephalosporin ceftiofur. We evaluated relative potential efficacy of within- or outside-host biological interventions delivered throughout rearing depending on the targeted parameter of bacterial ecology. Most instrumental in reducing the fraction of resistant enteric E. coli at steer slaughter age were interventions acting on the enteric E. coli and capable of either 'plasmid curing' E. coli, or lowering maximum E. coli numbers or the rate of plasmid transfer in this habitat. Also efficient was to increase the regular replacement of enteric E. coli. Lowering replication rate of resistant E. coli alone was not an efficient intervention target.201323339899