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907400.9897BacAnt: A Combination Annotation Server for Bacterial DNA Sequences to Identify Antibiotic Resistance Genes, Integrons, and Transposable Elements. Whole genome sequencing (WGS) of bacteria has become a routine method in diagnostic laboratories. One of the clinically most useful advantages of WGS is the ability to predict antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) in bacterial sequences. This allows comprehensive investigations of such genetic features but can also be used for epidemiological studies. A plethora of software programs have been developed for the detailed annotation of bacterial DNA sequences, such as rapid annotation using subsystem technology (RAST), Resfinder, ISfinder, INTEGRALL and The Transposon Registry. Unfortunately, to this day, a reliable annotation tool of the combination of ARGs and MGEs is not available, and the generation of genbank files requires much manual input. Here, we present a new webserver which allows the annotation of ARGs, integrons and transposable elements at the same time. The pipeline generates genbank files automatically, which are compatible with Easyfig for comparative genomic analysis. Our BacAnt code and standalone software package are available at https://github.com/xthua/bacant with an accompanying web application at http://bacant.net.202134367079
690910.9897Effect of meddling ARBs on ARGs dynamics in fungal infested soil and their selective dispersal along spatially distant mycelial networks. During the recent times, environmental antibiotic resistance genes (ARGs) and their potential transfer to other bacterial hosts of pathogenic importance are of serious concern. However, the dissemination strategies of such ARGs are largely unknown. We tested that saprotrophic soil fungi differentially enriched antibiotic resistant bacteria (ARBs) and subsequently contributed in spatial distribution of selective ARGs. Wafergen qPCR analysis of 295 different ARGs was conducted for manure treated pre-sterilized soil incubated or not with selected bacterial-fungal consortia. The qPCR assay detected unique ARGs specifically found in the mycosphere of ascomycetous and basidiomycetous fungi. Both fungi exerted potentially different selection pressures on ARBs, resulting in different patterns of ARGs dissemination (to distant places) along their respective growing fungal highways. The relative abundance of mobile genetic elements (MGEs) was significantly decreased along fungal highways compared to the respective inoculation points. Moreover, the decrease in MGEs and ARGs (along fungal highways) was more prominent over time which depicts the continuous selection pressure of growing fungi on ARBs for enrichment of particular ARGs in mycosphere. Such data also indicate the potential role of saprotrophic soil fungi to facilitate horizontal gene transfer within mycospheric environmental settings. Our study, therefore, advocates to emphasize the future investigations for such (bacteria-fungal) interactive microbial consortia for potential (spatial) dissemination of resistance determinants which may ultimately increase the exposure risks of ARGs.202438992349
908320.9896ARGNet: using deep neural networks for robust identification and classification of antibiotic resistance genes from sequences. BACKGROUND: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing. RESULTS: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG. CONCLUSIONS: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract.202438725076
743730.9895Bacteriophages vehiculate a high amount of antibiotic resistance determinants of bacterial origin in the Orne River ecosystem. Aquatic environments are important dissemination routes of antibiotic resistance genes (ARGs) from and to pathogenic bacteria. Nevertheless, in these complex matrices, identifying and characterizing the driving microbial actors and ARG dissemination mechanisms they are involved in remain difficult. We here explored the distribution/compartmentalization of a panel of ARGs and mobile genetic elements (MGEs) in bacteria and bacteriophages collected in the water, suspended material and surface sediments from the Orne River ecosystem (France). By using a new bacteriophage DNA extraction method, we showed that, when packaging bacterial DNA, bacteriophages rather encapsidate both ARGs and MGEs than 16S rRNA genes, i.e. chromosomal fragments. We also show that the bacteria and bacteriophage capsid contents in ARGs/MGEs were similarly influenced by seasonality but that the distribution of ARGs/MGEs between the river physical compartments (water vs. suspended mater vs. sediment) is more impacted when these markers were carried by bacteria. These demonstrations will likely modify our understanding of the formation and fate of transducing viral particles in the environment. Consequently, they will also likely modify our estimations of the relative frequencies of the different horizontal gene transfer mechanisms in disseminating antibiotic resistance by reinforcing the roles played by environmental bacteriophages and transduction.202235672875
648440.9894Microbial assisted phytodepuration for water reclamation: Environmental benefits and threats. Climate changes push for water reuse as a priority to counteract water scarcity and minimize water footprint especially in agriculture, one of the highest water consuming human activities. Phytodepuration is indicated as a promising technology for water reclamation, also in the light of its economic and ecological sustainability, and the use of specific bacterial inocula for microbial assisted phytodepuration has been proposed as a further advance for its implementation. Here we provided an overview on the selection and use of plant growth promoting bacteria in Constructed Wetland (CW) systems, showing their advantages in terms of plant growth support and pollutant degradation abilities. Moreover, CWs are also proposed for the removal of emerging organic pollutants like antibiotics from urban wastewaters. We focused on this issue, still debated in the literature, revealing the necessity to deepen the knowledge on the antibiotic resistance spread into the environment in relation to treated wastewater release and reuse. In addition, given the presence in the plant system of microhabitats (e.g. rhizosphere) that are hot spot for Horizontal Gene Transfer, we highlighted the importance of gene exchange to understand if these events can promote the diffusion of antibiotic resistance genes and antibiotic resistant bacteria, possibly entering in the food production chain when treated wastewater is used for irrigation. Ideally, this new knowledge will lead to improve the design of phytodepuration systems to maximize the quality and safety of the treated effluents in compliance with the 'One Health' concept.202031605997
642250.9894Is the application of organic fertilizers becoming an undeniable source of microplastics and resistance genes in agricultural systems? The application of organic fertilizers is becoming an undeniable source of microplastics and antibiotic resistance genes (ARGs) in agricultural soils. The complex microbial activity further transfers resistance genes and their host bacteria to agricultural products and throughout the entire food chain. Therefore, the current main focus is on reducing the abundance of microplastics and ARGs in organic fertilizers at the source, as well as managing microplastics and ARGs in soil. The control of microplastic abundance in organic fertilizers is currently only achieved through pre-composting selection and other methods. However, there are still many shortcomings in the research on the distribution characteristics, propagation and diffusion mechanisms, and control technologies of ARGs, and some key scientific issues still need to be urgently addressed. The high-temperature composting of organic waste can effectively reduce the abundance of ARGs in organic fertilizers to a certain extent. However, it is also important to consider the spread of ARGs in residual antibiotic-resistant bacteria (ARB). This article systematically explores the pathways and interactions of microplastics and resistance genes entering agricultural soils through the application of organic fertilizers. The removal of microplastics and ARGs from organic fertilizers was discussed in detail. Based on the limitations of existing research, further investigation in this area is expected to provide valuable insights for the development and practical implementation of technologies aimed at reducing soil microplastics and resistance genes.202438142997
962560.9894Water chlorination increases the relative abundance of an antibiotic resistance marker in developing sourdough starters. Multiple factors explain the proper development of sourdough starters. Although the role of raw ingredients and geography, among other things, have been widely studied recently, the possible effect of air quality and water chlorination on the overall bacterial communities associated with sourdough remains to be explored. Here, using 16S rRNA amplicon sequencing, we show that clean, filtered-air severely limited the presence of lactic acid bacteria in sourdough starters, suggesting that surrounding air is an important source of microorganisms necessary for the development of sourdough starters. We also show that water chlorination at levels commonly found in drinking water systems has a limited impact on the overall bacterial communities developing in sourdough starters. However, using targeted sequencing, which offers a higher resolution, we found that the abundance of integron 1, a genetic mechanism responsible for the horizontal exchange of antibiotic-resistance genes in spoilage and pathogenic bacteria, increased significantly with the level of water chlorination. Although our results suggest that water chlorination might not impact sourdough starters at a deep phylogenetic level, they indicate that it can favor the spread of genetic elements associated with spoilage bacteria. IMPORTANCE: Proper development of sourdough starters is critical for making tasty and healthy bread. Although many factors contributing to sourdough development have been studied, the effect of water chlorination on the bacterial communities in sourdough has been largely ignored. Researchers used sequencing techniques to investigate this effect and found that water chlorination at levels commonly found in drinking water systems has a limited impact on the overall bacterial communities developing in sourdough starters. However, they discovered that water chlorination could increase the abundance of integron 1, a genetic mechanism responsible for the horizontal exchange of antibiotic resistance genes in spoilage and pathogenic bacteria. This suggests that water chlorination could favor the growth of key spoilage bacteria and compromise the quality and safety of the bread. These findings emphasize the importance of considering water quality when developing sourdough starters for the best possible bread.202439283274
863070.9894Environmental fate and behaviour of antibiotic resistance genes and small interference RNAs released from genetically modified crops. Rising global populations have amplified food scarcity across the world and ushered in the development of genetically modified (GM) crops to overcome these challenges. Cultivation of major crops such as corn and soy has favoured GM crops over conventional varieties to meet crop production and resilience needs. Modern GM crops containing small interference RNA molecules and antibiotic resistance genes have become increasingly common in the United States. However, the use of these crops remains controversial due to the uncertainty regarding the unintended release of its genetic material into the environment and possible downstream effects on human and environmental health. DNA or RNA transgenes may be exuded from crop tissues during cultivation or released during plant decomposition and adsorbed by soil. This can contribute to the persistence and bioavailability in soil or water environment and possible uptake by soil microbial communities and further passing of this information to neighbouring bacteria, disrupting microbial ecosystem services such as nutrient cycling and soil fertility. In this review, transgene mechanisms of action, uses in crops, and knowledge regarding their environmental fate and impact to microbes are evaluated. This aims to encapsulate the current knowledge and promote further research regarding unintended effects transgenes may cause.202235892194
944980.9893Conclusions and activities of previous expert groups: the Scientific Steering Committee of the EU. In 1998, the EU Commission consulted its Scientific Steering Committee (SSC) to give advice on actions against anti-microbial resistance based on scientific evidence. The SSC set up a working group and adopted in 1999 an Opinion on Antimicrobial Resistance. Statements given in the well-structured document are clear, and precise recommendations were proposed. Summarizing, the Committee stated: There is evidence to suppose a continuous flow of resistance genes between pathogenic and commensal bacteria and of transfer of these bacteria between different compartments of the biosphere, thus changing the genetic resources continuously. There exist numerous factors which influence the emergence and spread of anti-bacterial resistance. However, it is likely that restriction in the use of anti-microbials will lead to a containment or a reduction of the drug resistance problem. Actions should be taken promptly to reduce the overall use of anti-microbials in a balanced way in all areas: human medicine, veterinary medicine, animal production and plant protection.200415525374
862990.9893Antibiotic resistance in plant growth promoting bacteria: A comprehensive review and future perspectives to mitigate potential gene invasion risks. Plant growth-promoting bacteria (PGPB) are endowed with several attributes that can be beneficial for host plants. They opened myriad doors toward green technology approach to reduce the use of chemical inputs, improve soil fertility, and promote plants' health. However, many of these PGPB harbor antibiotic resistance genes (ARGs). Less attention has been given to multi-resistant bacterial bioinoculants which may transfer their ARGs to native soil microbial communities and other environmental reservoirs including animals, waters, and humans. Therefore, large-scale inoculation of crops by ARGs-harboring bacteria could worsen the evolution and dissemination of antibiotic resistance and aggravate the negative impacts on such ecosystem and ultimately public health. Their introduction into the soil could serve as ARGs invasion which may inter into the food chain. In this review, we underscore the antibiotic resistance of plant-associated bacteria, criticize the lack of consideration for this phenomenon in the screening and application processes, and provide some recommendations as well as a regulation framework relating to the development of bacteria-based biofertilizers to aid maximizing their value and applications in crop improvement while reducing the risks of ARGs invasion.202236204627
6393100.9893A review of the impact of conductive materials on antibiotic resistance genes during the anaerobic digestion of sewage sludge and animal manure. The urgent need to reduce the environmental burden of antibiotic resistance genes (ARGs) has become even more apparent as concerted efforts are made globally to tackle the dissemination of antimicrobial resistance. Concerning levels of ARGs abound in sewage sludge and animal manure, and their inadequate attenuation during conventional anaerobic digestion (AD) compromises the safety of the digestate, a nutrient-rich by-product of AD commonly recycled to agricultural land for improvement of soil quality. Exogenous ARGs introduced into the natural environment via the land application of digestate can be transferred from innocuous environmental bacteria to clinically relevant bacteria by horizontal gene transfer (HGT) and may eventually reach humans through food, water, and air. This review, therefore, discusses the prospects of using carbon- and iron-based conductive materials (CMs) as additives to mitigate the proliferation of ARGs during the AD of sewage sludge and animal manure. The review spotlights the core mechanisms underpinning the influence of CMs on the resistome profile, the steps to maximize ARG attenuation using CMs, and the current knowledge gaps. Data and information gathered indicate that CMs can profoundly reduce the abundance of ARGs in the digestate by easing selective pressure on ARGs, altering microbial community structure, and diminishing HGT.202336586329
6635110.9893Antimicrobial resistance dashboard application for mapping environmental occurrence and resistant pathogens. An antibiotic resistance (AR) Dashboard application is being developed regarding the occurrence of antibiotic resistance genes (ARG) and bacteria (ARB) in environmental and clinical settings. The application gathers and geospatially maps AR studies, reported occurrence and antibiograms, which can be downloaded for offline analysis. With the integration of multiple data sets, the database can be used on a regional or global scale to identify hot spots for ARGs and ARB; track and link spread and transmission, quantify environmental or human factors influencing presence and persistence of ARG harboring organisms; differentiate natural ARGs from those distributed via human or animal activity; cluster and compare ARGs connections in different environments and hosts; and identify genes that can be used as proxies to routinely monitor anthropogenic pollution. To initially populate and develop the AR Dashboard, a qPCR ARG array was tested with 30 surface waters, primary influent from three waste water treatment facilities, ten clinical isolates from a regional hospital and data from previously published studies including river, park soil and swine farm samples. Interested users are invited to download a beta version (available on iOS or Android), submit AR information using the application, and provide feedback on current and prospective functionalities.201626850162
8163120.9893Green materials science and engineering reduces biofouling: approaches for medical and membrane-based technologies. Numerous engineered and natural environments suffer deleterious effects from biofouling and/or biofilm formation. For instance, bacterial contamination on biomedical devices pose serious health concerns. In membrane-based technologies, such as desalination and wastewater reuse, biofouling decreases membrane lifetime, and increases the energy required to produce clean water. Traditionally, approaches have combatted bacteria using bactericidal agents. However, due to globalization, a decline in antibiotic discovery, and the widespread resistance of microbes to many commercial antibiotics and metallic nanoparticles, new materials, and approaches to reduce biofilm formation are needed. In this mini-review, we cover the recent strategies that have been explored to combat microbial contamination without exerting evolutionary pressure on microorganisms. Renewable feedstocks, relying on structure-property relationships, bioinspired/nature-derived compounds, and green processing methods are discussed. Greener strategies that mitigate biofouling hold great potential to positively impact human health and safety.201525852659
6438130.9892The influence of heavy metals, polyaromatic hydrocarbons, and polychlorinated biphenyls pollution on the development of antibiotic resistance in soils. The minireview is devoted to the analysis of the influence of soil pollution with heavy metals, polyaromatic hydrocarbons (PAHs), and the polychlorinated biphenyls (PCBs) on the distribution of antibiotics resistance genes (ARGs) in soil microbiomes. It is shown that the best understanding of ARGs distribution process requires studying the influence of pollutants on this process in natural microbiocenoses. Heavy metals promote co-selection of genes determining resistance to them together with ARGs in the same mobile elements of a bacterial genome, but the majority of studies focus on agricultural soils enriched with ARGs originating from manure. Studying nonagricultural soils would clear mechanisms of ARGs transfer in natural and anthropogenically transformed environments and highlight the role of antibiotic-producing bacteria. PAHs make a considerable shift in soil microbiomes leading to an increase in the number of Actinobacteria which are the source of antibiotics formation and bear multiple ARGs. The soils polluted with PAHs can be a selective medium for bacteria resistant to antibiotics, and the level of ARGs expression is much higher. PCBs are accumulated in soils and significantly alter the specific structure of soil microbiocenoses. In such soils, representatives of the genera Acinetobacter, Pseudomonas, and Alcanivorax dominate, and the ability to degrade PCBs is connected to horizontal gene transfer (HGT) and high level of genomic plasticity. The attention is also focused on the need to study the properties of the soil having an impact on the bioavailability of pollutants and, as a result, on resistome of soil microorganisms.201829453715
6418140.9892Antibiotic resistance genes in anaerobic digestion: Unresolved challenges and potential solutions. Antimicrobial resistance (AMR) threatens public health, necessitating urgent efforts to mitigate the global impact of antibiotic resistance genes (ARGs). Anaerobic digestion (AD), known for volatile solid reduction and energy generation, also presents a feasible approach for the removal of ARGs. This review encapsulates the existing understanding of ARGs and antibiotic-resistant bacteria (ARB) during the AD process, highlighting unresolved challenges pertaining to their detection and quantification. The questions raised and discussed include: Do current ARGs detection methods meet qualitative and quantitative requirements? How can we conduct risk assessments of ARGs? What happens to ARGs when they come into co-exposure with other emerging pollutants? How can the application of internal standards bolster the reliability of the AD resistome study? What are the potential future research directions that could enhance ARG elimination? Investigating these subjects will assist in shaping more efficient management strategies that employ AD for effective ARG control.202539826759
8575150.9892Key factors driving the fate of antibiotic resistance genes and controlling strategies during aerobic composting of animal manure: A review. Occurrence of antibiotic resistance genes (ARGs) in animal manure impedes the reutilization of manure resources. Aerobic composting is potentially effective method for resource disposal of animal manure, but the fate of ARGs during composting is complicated due to the various material sources and different operating conditions. This review concentrates on the biotic and abiotic factors influencing the variation of ARGs in composting and their potential mechanisms. The dynamic variations of biotic factors, including bacterial community, mobile genetic elements (MGEs) and existence forms of ARGs, are the direct driving factors of the fate of ARGs during composting. However, most key abiotic indicators, including pH, moisture content, antibiotics and heavy metals, interfere with the richness of ARGs indirectly by influencing the succession of bacterial community and abundance of MGEs. The effect of temperature on ARGs depends on whether the ARGs are intracellular or extracellular, which should be paid more attention. The emergence of various controlling strategies renders the composting products safer. Four potential removal mechanisms of ARGs in different controlling strategies have been concluded, encompassing the attenuation of selective/co-selective pressure on ARGs, killing the potential host bacteria of ARGs, reshaping the structure of bacterial community and reducing the cell-to-cell contact of bacteria. With the effective control of ARGs, aerobic composting is suggested to be a sustainable and promising approach to treat animal manure.202134139488
6634160.9892Making waves: The NORMAN antibiotic resistant bacteria and resistance genes database (NORMAN ARB&ARG)-An invitation for collaboration to tackle antibiotic resistance. With the global concerns on antibiotic resistance (AR) as a public health issue, it is pivotal to have data exchange platforms for studies on antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the environment. For this purpose, the NORMAN Association is hosting the NORMAN ARB&ARG database, which was developed within the European project ANSWER. The present article provides an overview on the database functionalities, the extraction and the contribution of data to the database. In this study, AR data from three studies from China and Nepal were extracted and imported into the NORMAN ARB&ARG in addition to the existing AR data from 11 studies (mainly European studies) on the database. This feasibility study demonstrates how the scientific community can share their data on AR to generate an international evidence base to inform AR mitigation strategies. The open and FAIR data are of high potential relevance for regulatory applications, including the development of emission limit values / environmental quality standards in relation to AR. The growth in sharing of data and analytical methods will foster collaboration on risk management of AR worldwide, and facilitate the harmonization in the effort for identification and surveillance of critical hotspots of AR. The NORMAN ARB&ARG database is publicly available at: https://www.norman-network.com/nds/bacteria/.202438723350
7451170.9892Plant species influences the composition of root system microbiome and its antibiotic resistance profile in a constructed wetland receiving primary treated wastewater. INTRODUCTION: Constructed wetlands (CWs) are nature-based solutions for wastewater treatment where the root system microbiome plays a key role in terms of nutrient and pollutant removal. Nonetheless, little is known on plant-microbe interactions and bacterial population selection in CWs, which are mostly characterized in terms of engineering aspects. METHODS: Here, cultivation-independent and cultivation-based analyses were applied to study the bacterial communities associated to the root systems of Phragmites australis and Typha domingensis co-occurring in the same cell of a CW receiving primary treated wastewaters. RESULTS AND DISCUSSION: Two endophytic bacteria collections (n = 156) were established aiming to find novel strains for microbial-assisted phytodepuration, however basing on their taxonomy the possible use of these strains was limited by their low degrading potential and/or for risks related to the One-Health concept. A sharp differentiation arose between the P. australis and T. domingensis collections, mainly represented by lactic acid bacteria (98%) and Enterobacteriaceae (69%), respectively. Hence, 16S rRNA amplicon sequencing was used to disentangle the microbiome composition in the root system fractions collected at increasing distance from the root surface. Both the fraction type and the plant species were recognized as drivers of the bacterial community structure. Moreover, differential abundance analysis revealed that, in all fractions, several bacteria families were significantly and differentially enriched in P. australis or in T. domingensis. CWs have been also reported as interesting options for the removal of emerging contaminants (e.g, antibiotic resistance genes, ARGs). In this study, ARGs were mostly present in the rhizosphere of both plant species, compared to the other analyzed fractions. Notably, qPCR data showed that ARGs (i.e., ermB, bla (TEM), tetA) and intl1 gene (integrase gene of the class 1 integrons) were significantly higher in Phragmites than Typha rhizospheres, suggesting that macrophyte species growing in CWs can display a different ability to remove ARGs from wastewater. Overall, the results suggest the importance to consider the plant-microbiome interactions, besides engineering aspects, to select the most suitable species when designing phytodepuration systems.202439113842
6445180.9892Microplastics: Disseminators of antibiotic resistance genes and pathogenic bacteria. Microplastics (MPs) are emerging pollutants that linger in the air, water, and land. Beyond their physical and chemical risks, there is growing evidence that MPs contribute to the worldwide antimicrobial resistance (AMR) dilemma by acting as carriers of harmful microbes and antibiotic resistance genes (ARGs). Despite an increase in research, the available literature is dispersed, and the part that MPs play in influencing microbial populations and fostering resistance is still not well understood. This review summarizes current research on how MPs contribute to the spread of antibiotic resistance. We concentrated on the ways in which MPs support horizontal gene transfer (HGT) processes such as conjugation, transformation, and transduction, assist biofilm development, and offer surfaces for microbial colonization. Evidence from a variety of settings suggests that MPs serve as vectors for opportunistic pathogens, such as the ESKAPE group, and ARGs, increasing the survival and movement of resistance determinants in ecosystems. Through the consolidation of current developments, this review emphasizes MPs as active resistance vectors instead of passive pollutants. We also point out important limitations, such as the lack of standardized procedures, inadequate risk assessment frameworks, and the absence of real-world exposure research. It is imperative that these issues be approached from a One Health standpoint in order to reduce the risks of both plastic pollution and antibiotic resistance.202541056605
6714190.9892Differential Drivers of Antimicrobial Resistance across the World. Antimicrobial resistance (AMR) is one of the greatest threats faced by humankind. The development of resistance in clinical and hospital settings has been well documented ever since the initial discovery of penicillin and the subsequent introduction of sulfonamides as clinical antibiotics. In contrast, the environmental (i.e., community-acquired) dimensions of resistance dissemination have been only more recently delineated. The global spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) between air, water, soil, and food is now well documented, while the factors that affect ARB and ARG dissemination (e.g., water and air quality, antibiotic fluxes, urbanization, sanitation practices) in these and other environmental matrices are just now beginning to be more fully appreciated. In this Account, we discuss how the global perpetuation of resistance is dictated by highly interconnected socioeconomic risk factors and illustrate that development status should be more fully considered when developing global strategies to address AMR. We first differentiate low to middle income countries (LMICs) and high-income countries (HICs), then we summarize the modes of action of commercially available antibiotics, and then discuss the four primary mechanisms by which bacteria develop resistance to those antibiotics. Resistance is disseminated via both vertical gene transfer (VGT; parent to offspring) as well as by horizontal gene transfer (HGT; cell to cell transference of genetic material). A key challenge hindering attempts to control resistance dissemination is the presence of native, environmental bacteria that can harbor ARGs. Such environmental "resistomes" have potential to transfer resistance to pathogens via HGT. Of particular concern is the development of resistance to antibiotics of last-resort such as the cephalosporins, carbapenems, and polymyxins. We then illustrate how antibiotic use differs in LMICs relative to HICs in terms of the volumes of antibiotics used and their fate within local environments. Antibiotic use in HICs has remained flat over the past 15 years, while in LMICs use over the same period has increased substantially as a result of economic improvements and changes in diet. These use and fate differences impact local citizens and thus the local dissemination of AMR. Various physical, social, and economic circumstances within LMICs potentially favor AMR dissemination. We focus on three physical factors: changing population density, sanitation infrastructure, and solid-waste disposal. We show that high population densities in cities within LMICs that suffer from poor sanitation and solid-waste disposal can potentially impact the dissemination of resistance. In the final section, we discuss potential monitoring approaches to quantify the spread of resistance both within LMICs as well as in HICs. We posit that culture-based approaches, molecular approaches, and cutting-edge nanotechnology-based methods for monitoring ARB and ARGs should be considered both within HICs and, as appropriate, within LMICs.201930848890