Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge. - Related Documents




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333701.0000Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge. The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where such initial mobilization events of clinically relevant ARGs may have occurred. We found that the majority of previously identified origin species did not carry the mobilizing elements that likely enabled intracellular mobility of the ARGs, suggesting a necessary interplay between different bacteria. Analyses of a broad range of metagenomes revealed that wastewaters and wastewater-impacted environments had by far the highest abundance of both origin species and corresponding mobilizing elements. Most origin species were only occasionally detected in other environments. Co-occurrence of origin species and corresponding mobilizing elements were rare in human microbiota. Our results identify wastewaters and wastewater-impacted environments as plausible arenas for the initial mobilization of resistance genes.202336966231
334210.9999Marine sediment bacteria harbor antibiotic resistance genes highly similar to those found in human pathogens. The ocean is a natural habitat for antibiotic-producing bacteria, and marine aquaculture introduces antibiotics into the ocean to treat infections and improve aquaculture production. Studies have shown that the ocean is an important reservoir of antibiotic resistance genes. However, there is a lack of understanding and knowledge about the clinical importance of the ocean resistome. We investigated the relationship between the ocean bacterial resistome and pathogenic resistome. We applied high-throughput sequencing and metagenomic analyses to explore the resistance genes in bacterial plasmids from marine sediments. Numerous putative resistance determinants were detected among the resistance genes in the sediment bacteria. We also found that several contigs shared high identity with transposons or plasmids from human pathogens, indicating that the sediment bacteria recently contributed or acquired resistance genes from pathogens. Marine sediment bacteria could play an important role in the global exchange of antibiotic resistance.201323370726
334120.9999The shared resistome of human and pig microbiota is mobilized by distinct genetic elements. The extensive use of antibiotics in hospitals and in the animal breeding industry has promoted antibiotic resistance in bacteria, which resulted in the emergence of a large number of antibiotic resistance genes in the intestinal tract of human and farmed animals. Genetic exchange of resistance genes between the two ecosystems is now well documented for pathogenic bacteria, but the repertoire of shared resistance genes in the commensal bacterial community and by which genetic modules they are disseminated are still unclear. By analyzing metagenomics data of human and pig intestinal samples both collected in Shenzhen, China, a set of 27 highly prevalent antibiotic resistance genes was found to be shared between human and pig intestinal microbiota. The mobile genetic context for 11 of these core antibiotic resistance genes could be identified by mining their carrying scaffolds constructed from the two datasets, leading to the detection of seven integrative and conjugative/mobilizable elements and two IS-related transposons. The comparison of the relative abundances between these detected mobile genetic elements and their associated antibiotic resistance genes revealed that for many genes, the estimated contribution of the mobile elements to the gene abundance differs strikingly depending on the host. These findings indicate that although some antibiotic resistance genes are ubiquitous across microbiota of human and pig populations, they probably relied on different genetic elements for their dissemination within each population.IMPORTANCE There is growing concern that antibiotic resistance genes could spread from the husbandry environment to human pathogens through dissemination mediated by mobile genetic elements. In this study, we investigated the contribution of mobile genetic elements to the abundance of highly prevalent antibiotic resistance genes found in commensal bacteria of both human and pig intestinal microbiota originating from the same region. Our results reveal that for most of these antibiotic resistance genes, the abundance is not explained by the same mobile genetic element in each host, suggesting that the human and pig microbial communities promoted a different set of mobile genetic carriers for the same antibiotic resistance genes. These results deepen our understanding of the dissemination of antibiotic resistance genes among and between human and pig gut microbiota.202133310720
399730.9999Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements. The high and sometimes inappropriate use of antibiotics has accelerated the development of antibiotic resistance, creating a major challenge for the sustainable treatment of infections world-wide. Bacterial communities often respond to antibiotic selection pressure by acquiring resistance genes, i.e. mobile genetic elements that can be shared horizontally between species. Environmental microbial communities maintain diverse collections of resistance genes, which can be mobilized into pathogenic bacteria. Recently, exceptional environmental releases of antibiotics have been documented, but the effects on the promotion of resistance genes and the potential for horizontal gene transfer have yet received limited attention. In this study, we have used culture-independent shotgun metagenomics to investigate microbial communities in river sediments exposed to waste water from the production of antibiotics in India. Our analysis identified very high levels of several classes of resistance genes as well as elements for horizontal gene transfer, including integrons, transposons and plasmids. In addition, two abundant previously uncharacterized resistance plasmids were identified. The results suggest that antibiotic contamination plays a role in the promotion of resistance genes and their mobilization from environmental microbes to other species and eventually to human pathogens. The entire life-cycle of antibiotic substances, both before, under and after usage, should therefore be considered to fully evaluate their role in the promotion of resistance.201121359229
747840.9999Global analysis of the metaplasmidome: ecological drivers and spread of antibiotic resistance genes across ecosystems. BACKGROUND: Plasmids act as vehicles for the rapid spread of antibiotic resistance genes (ARGs). However, few studies of the resistome at the community level distinguish between ARGs carried by mobile genetic elements and those carried by chromosomes, and these studies have been limited to a few ecosystems. This is the first study to focus on ARGs carried by the metaplasmidome on a global scale. RESULTS: This study shows that only a small fraction of the plasmids reconstructed from 27 ecosystems representing 9 biomes are catalogued in public databases. The abundance of ARGs harboured by the metaplasmidome was significantly explained by bacterial richness. Few plasmids with or without ARGs were shared between ecosystems or biomes, suggesting that plasmid distribution on a global scale is mainly driven by ecology rather than geography. The network linking plasmids to their hosts shows that these mobile elements have thus been shared between bacteria across geographically distant environmental niches. However, certain plasmids carrying ARGs involved in human health were identified as being shared between multiple ecosystems and hosted by a wide variety of hosts. Some of these mobile elements, identified as keystone plasmids, were characterised by an enrichment in antibiotic resistance genes (ARGs) and CAS-CRISPR components which may explain their ecological success. The ARGs accounted for 9.2% of the recent horizontal transfers between bacteria and plasmids. CONCLUSIONS: By comprehensively analysing the plasmidome content of ecosystems, some key habitats have emerged as particularly important for monitoring the spread of ARGs in relation to human health. Of particular note is the potential for air to act as a vector for long-distance transport of ARGs and accessory genes across ecosystems and continents. Video Abstract.202540108678
333650.9999Suspended Materials in River Waters Differentially Enrich Class 1 Integron- and IncP-1 Plasmid-Carrying Bacteria in Sediments. Aquatic ecosystems are frequently considered as the final receiving environments of anthropogenic pollutants such as pharmaceutical residues or antibiotic resistant bacteria, and as a consequence tend to form reservoirs of antibiotic resistance genes. Considering the global threat posed by the antibiotic resistance, the mechanisms involved in both the formation of such reservoirs and their remobilization are a concern of prime importance. Antibiotic resistance genes are strongly associated with mobile genetic elements that are directly involved in their dissemination. Most mobile genetic element-mediated gene transfers involve replicative mechanisms and, as such, localized gene transfers should participate in the local increase in resistance gene abundance. Additionally, the carriage of conjugative mobile elements encoding cell appendages acting as adhesins has already been demonstrated to increase biofilm-forming capability of bacteria and, therefore, should also contribute to their selective enrichment on surfaces. In the present study, we investigated the occurrence of two families of mobile genetic elements, IncP-1 plasmids and class 1 integrons, in the water column and bank sediments of the Orne River, in France. We show that these mobile elements, especially IncP-1 plasmids, are enriched in the bacteria attached on the suspended matters in the river waters, and that a similar abundance is found in freshly deposited sediments. Using the IncP-1 plasmid pB10 as a model, in vitro experiments demonstrated that local enrichment of plasmid-bearing bacteria on artificial surfaces mainly resulted from an increase in bacterial adhesion properties conferred by the plasmid rather than an improved dissemination frequency of the plasmid between surface-attached bacteria. We propose plasmid-mediated adhesion to particles to be one of the main contributors in the formation of mobile genetic element-reservoirs in sediments, with adhesion to suspended matter working as a selective enrichment process of antibiotic resistant genes and bacteria.201830013540
390960.9999Biosolids as a Source of Antibiotic Resistance Plasmids for Commensal and Pathogenic Bacteria. Antibiotic resistance (AR) is a threat to modern medicine, and plasmids are driving the global spread of AR by horizontal gene transfer across microbiomes and environments. Determining the mobile resistome responsible for this spread of AR among environments is essential in our efforts to attenuate the current crisis. Biosolids are a wastewater treatment plant (WWTP) byproduct used globally as fertilizer in agriculture. Here, we investigated the mobile resistome of biosolids that are used as fertilizer. This was done by capturing resistance plasmids that can transfer to human pathogens and commensal bacteria. We used a higher-throughput version of the exogenous plasmid isolation approach by mixing several ESKAPE pathogens and a commensal Escherichia coli with biosolids and screening for newly acquired resistance to about 10 antibiotics in these strains. Six unique resistance plasmids transferred to Salmonella typhimurium, Klebsiella aerogenes, and E. coli. All the plasmids were self-transferable and carried 3-6 antibiotic resistance genes (ARG) conferring resistance to 2-4 antibiotic classes. These plasmids-borne resistance genes were further embedded in genetic elements promoting intracellular recombination (i.e., transposons or class 1 integrons). The plasmids belonged to the broad-host-range plasmid (BHR) groups IncP-1 or PromA. Several of them were persistent in their new hosts when grown in the absence of antibiotics, suggesting that the newly acquired drug resistance traits would be sustained over time. This study highlights the role of BHRs in the spread of ARG between environmental bacteria and human pathogens and commensals, where they may persist. The work further emphasizes biosolids as potential vehicles of highly mobile plasmid-borne antibiotic resistance genes.202133967971
965070.9999Plasmid-Encoded Traits Vary across Environments. Plasmids are key mobile genetic elements in bacterial evolution and ecology as they allow the rapid adaptation of bacteria under selective environmental changes. However, the genetic information associated with plasmids is usually considered separately from information about their environmental origin. To broadly understand what kinds of traits may become mobilized by plasmids in different environments, we analyzed the properties and accessory traits of 9,725 unique plasmid sequences from a publicly available database with known bacterial hosts and isolation sources. Although most plasmid research focuses on resistance traits, such genes made up <1% of the total genetic information carried by plasmids. Similar to traits encoded on the bacterial chromosome, plasmid accessory trait compositions (including general Clusters of Orthologous Genes [COG] functions, resistance genes, and carbon and nitrogen genes) varied across seven broadly defined environment types (human, animal, wastewater, plant, soil, marine, and freshwater). Despite their potential for horizontal gene transfer, plasmid traits strongly varied with their host's taxonomic assignment. However, the trait differences across environments of broad COG categories could not be entirely explained by plasmid host taxonomy, suggesting that environmental selection acts on the plasmid traits themselves. Finally, some plasmid traits and environments (e.g., resistance genes in human-related environments) were more often associated with mobilizable plasmids (those having at least one detected relaxase) than others. Overall, these findings underscore the high level of diversity of traits encoded by plasmids and provide a baseline to investigate the potential of plasmids to serve as reservoirs of adaptive traits for microbial communities. IMPORTANCE Plasmids are well known for their role in the transmission of antibiotic resistance-conferring genes. Beyond human and clinical settings, however, they disseminate many other types of genes, including those that contribute to microbially driven ecosystem processes. In this study, we identified the distribution of traits genetically encoded by plasmids isolated from seven broadly categorized environments. We find that plasmid trait content varied with both bacterial host taxonomy and environment and that, on average, half of the plasmids were potentially mobilizable. As anthropogenic activities impact ecosystems and the climate, investigating and identifying the mechanisms of how microbial communities can adapt will be imperative for predicting the impacts on ecosystem functioning.202336629415
334080.9999Viruses as key reservoirs of antibiotic resistance genes in the environment. Antibiotic resistance is a rapidly growing health care problem globally and causes many illnesses and deaths. Bacteria can acquire antibiotic resistance genes (ARGs) by horizontal transfer mediated by mobile genetic elements, where the role of phages in their dissemination in natural environments has not yet been clearly resolved. From metagenomic studies, we showed that the mean proportion of predicted ARGs found in prophages (0-0.0028%) was lower than those present in the free viruses (0.001-0.1%). Beta-lactamase, from viruses in the swine gut, represented 0.10 % of the predicted genes. Overall, in the environment, the ARG distribution associated with viruses was strongly linked to human activity, and the low dN/dS ratio observed advocated for a negative selection of the ARGs harbored by the viruses. Our network approach showed that viruses were linked to putative pathogens (Enterobacterales and vibrionaceae) and were considered key vehicles in ARG transfer, similar to plasmids. Therefore, these ARGs could then be disseminated at larger temporal and spatial scales than those included in the bacterial genomes, allowing for time-delayed genetic exchanges.201931358910
405490.9999Ecological impact of antibiotic use in animals on different complex microflora: environment. Different means of interaction between microecological systems in different animal hosts (including humans) and the environment may occur during the transfer of resistant bacteria and their resistance genes. Spread of resistance takes place in different ways with respect to clonal spread of resistance strains by the spread of wide host range plasmids and translocatable elements. Commensals in ecosystems have a special significance and a pronounced capacity for acquisition and transfer of resistance genes as with Enterococcus faecium and Escherichia coli in the gut flora or Pseudomonas spp. in aquatic environments. The route of transmission from animals to humans by meat products is well established. Other routes via water and food plants (vegetables) have been investigated less, although resistance genes transfer in aquatic environments as evidenced from sequence comparison of such genes (e.g. tetR, floR in Salmonella typhimurium DT104). Whether this is due to rare but important transfer events or whether there is a more frequent exchange in aquatic or terrestrial environments needs further elucidation.200010794954
3343100.9998Shotgun metagenomics reveals a wide array of antibiotic resistance genes and mobile elements in a polluted lake in India. There is increasing evidence for an environmental origin of many antibiotic resistance genes. Consequently, it is important to identify environments of particular risk for selecting and maintaining such resistance factors. In this study, we described the diversity of antibiotic resistance genes in an Indian lake subjected to industrial pollution with fluoroquinolone antibiotics. We also assessed the genetic context of the identified resistance genes, to try to predict their genetic transferability. The lake harbored a wide range of resistance genes (81 identified gene types) against essentially every major class of antibiotics, as well as genes responsible for mobilization of genetic material. Resistance genes were estimated to be 7000 times more abundant than in a Swedish lake included for comparison, where only eight resistance genes were found. The sul2 and qnrD genes were the most common resistance genes in the Indian lake. Twenty-six known and 21 putative novel plasmids were recovered in the Indian lake metagenome, which, together with the genes found, indicate a large potential for horizontal gene transfer through conjugation. Interestingly, the microbial community of the lake still included a wide range of taxa, suggesting that, across most phyla, bacteria has adapted relatively well to this highly polluted environment. Based on the wide range and high abundance of known resistance factors we have detected, it is plausible that yet unrecognized resistance genes are also present in the lake. Thus, we conclude that environments polluted with waste from antibiotic manufacturing could be important reservoirs for mobile antibiotic resistance genes.201425520706
3779110.9998The transfer of antibiotic resistance genes between evolutionarily distant bacteria. Infections from antibiotic-resistant bacteria threaten human health globally. Resistance is often caused by mobile antibiotic resistance genes (ARGs) shared horizontally between bacterial genomes. Many ARGs originate from environmental and commensal bacteria and are transferred between divergent bacterial hosts before they reach pathogens. This process remains, however, poorly understood, which complicates the development of countermeasures that reduce the spread of ARGs. In this study, we aimed to systematically analyze the ARGs transferred between the most evolutionarily distant bacteria, defined here based on their phylum. We implemented an algorithm that identified inter-phylum transfers (IPTs) by combining ARG-specific phylogenetic trees with the taxonomy of the bacterial hosts. From the analysis of almost 1 million ARGs identified in >400,000 bacterial genomes, we identified 661 IPTs, which included transfers between all major bacterial phyla. The frequency of IPTs varies substantially between ARG classes and was highest for the aminoglycoside resistance gene AAC(3), while the levels for beta-lactamases were generally lower. ARGs involved in IPTs also differed between phyla, where, for example, tetracycline ARGs were commonly transferred between Firmicutes and Proteobacteria, but rarely between Actinobacteria and Proteobacteria. The results, furthermore, show that conjugative systems are seldom shared between bacterial phyla, suggesting that other mechanisms drive the dissemination of ARGs between divergent hosts. We also show that bacterial genomes involved in IPTs of ARGs are either over- or underrepresented in specific environments. These IPTs were also found to be more recent compared to transfers associated with bacteria isolated from water, soil, and sediment. While macrolide and tetracycline ARGs involved in IPTs almost always were >95% identical between phyla, corresponding β-lactamases showed a median identity of <60%. We conclude that inter-phylum transfer is recurrent, and our results offer new insights into how ARGs are disseminated between evolutionarily distant bacteria. IMPORTANCE: Antibiotic-resistant infections pose a growing threat to global health. This study reveals how genes conferring antibiotic resistance can move between bacteria that belong to different phyla lineages previously thought to be too evolutionarily distant for frequent gene exchange. By analyzing nearly 1 million resistance genes from over 400,000 bacterial genomes, the researchers uncovered hundreds of inter-phylum transfer events, exposing surprising patterns in how different classes of resistance genes spread. The findings highlight that conjugative systems are less common than expected in cross-phyla transfers and suggest that alternative mechanisms may play key roles. This new understanding of how resistance genes leap between vastly different bacterial groups can inform strategies to slow the emergence of drug-resistant infections, aiding in the development of more effective public health interventions.202540459279
3891120.9998On the use of antibiotics to control plant pathogenic bacteria: a genetic and genomic perspective. Despite growing attention, antibiotics (such as streptomycin, oxytetracycline or kasugamycin) are still used worldwide for the control of major bacterial plant diseases. This raises concerns on their potential, yet unknown impact on antibiotic and multidrug resistances and the spread of their genetic determinants among bacterial pathogens. Antibiotic resistance genes (ARGs) have been identified in plant pathogenic bacteria (PPB), with streptomycin resistance genes being the most commonly reported. Therefore, the contribution of mobile genetic elements (MGEs) to their spread among PPB, as well as their ability to transfer to other bacteria, need to be further explored. The only well-documented example of ARGs vector in PPB, Tn5393 and its highly similar variants (carrying streptomycin resistance genes), is concerning because of its presence outside PPB, in Salmonella enterica and Klebsiella pneumoniae, two major human pathogens. Although its structure among PPB is still relatively simple, in human- and animal-associated bacteria, Tn5393 has evolved into complex associations with other MGEs and ARGs. This review sheds light on ARGs and MGEs associated with PPB, but also investigates the potential role of antibiotic use in resistance selection in plant-associated bacteria.202337440885
3339130.9998Examining the taxonomic distribution of tetracycline resistance in a wastewater plant. Microbial communities serve as reservoirs of antibiotic resistance genes (ARGs) and facilitate the dissemination of these genes to bacteria that infect humans. Relatively little is known about the taxonomic distribution of bacteria harboring ARGs in these reservoirs and the avenues of transmission due to the technical hurdles associated with characterizing the contents of complex microbial populations and the assignment of genes to particular genomes. Focusing on the array of tetracycline resistance (Tc(r)) genes in the primary and secondary phases of wastewater treatment, 17 of the 22 assayed Tc(r) genes were detected in at least one sample. We then applied emulsion, paired isolation, and concatenation PCR (epicPCR) to link tetracycline resistance genes to specific bacterial hosts. Whereas Tc(r) genes tend to vary in their distributions among bacterial taxa according to their modes of action, there were numerous instances in which a particular Tc(r) gene was associated with a host that was distantly related to all other bacteria bearing the same gene, including several hosts not previously identified. Tc(r) genes are far less host-restricted than previously assumed, indicating that complex microbial communities serve as settings where ARGs are spread among divergent bacterial phyla.202438317688
3982140.9998Dissemination of antibiotic resistance genes (ARGs) via integrons in Escherichia coli: A risk to human health. With the induction of various emerging environmental contaminants such as antibiotic resistance genes (ARGs), environment is considered as a key indicator for the spread of antimicrobial resistance (AMR). As such, the ARGs mediated environmental pollution raises a significant public health concern worldwide. Among various genetic mechanisms that are involved in the dissemination of ARGs, integrons play a vital role in the dissemination of ARGs. Integrons are mobile genetic elements that can capture and spread ARGs among environmental settings via transmissible plasmids and transposons. Most of the ARGs are found in Gram-negative bacteria and are primarily studied for their potential role in antibiotic resistance in clinical settings. As one of the most common microorganisms, Escherichia coli (E. coli) is widely studied as an indicator carrying drug-resistant genes, so this article aims to provide an in-depth study on the spread of ARGs via integrons associated with E. coli outside clinical settings and highlight their potential role as environmental contaminants. It also focuses on multiple but related aspects that do facilitate environmental pollution, i.e. ARGs from animal sources, water treatment plants situated at or near animal farms, agriculture fields, wild birds and animals. We believe that this updated study with summarized text, will facilitate the readers to understand the primary mechanisms as well as a variety of factors involved in the transmission and spread of ARGs among animals, humans, and the environment.202032717638
3993150.9998Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics. Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment.201526356096
3996160.9998Antibiotic resistance gene spread due to manure application on agricultural fields. The usage of antibiotics in animal husbandry has promoted the development and abundance of antibiotic resistance in farm environments. Manure has become a reservoir of resistant bacteria and antibiotic compounds, and its application to agricultural soils is assumed to significantly increase antibiotic resistance genes and selection of resistant bacterial populations in soil. The genome location of resistance genes is likely to shift towards mobile genetic elements such as broad-host-range plasmids, integrons, and transposable elements. Horizontal transfer of these elements to bacteria adapted to soil or other habitats supports their environmental transmission independent of the original host. The human exposure to soil-borne resistance has yet to be determined, but is likely to be severely underestimated.201121546307
3995170.9998Bacterial diversity and antibiotic resistance in water habitats: searching the links with the human microbiome. Water is one of the most important bacterial habitats on Earth. As such, water represents also a major way of dissemination of bacteria between different environmental compartments. Human activities led to the creation of the so-called urban water cycle, comprising different sectors (waste, surface, drinking water), among which bacteria can hypothetically be exchanged. Therefore, bacteria can be mobilized between unclean water habitats (e.g. wastewater) and clean or pristine water environments (e.g. disinfected and spring drinking water) and eventually reach humans. In addition, bacteria can also transfer mobile genetic elements between different water types, other environments (e.g. soil) and humans. These processes may involve antibiotic resistant bacteria and antibiotic resistance genes. In this review, the hypothesis that some bacteria may share different water compartments and be also hosted by humans is discussed based on the comparison of the bacterial diversity in different types of water and with the human-associated microbiome. The role of such bacteria as potential disseminators of antibiotic resistance and the inference that currently only a small fraction of the clinically relevant antibiotic resistome may be known is discussed.201424484530
9649180.9998Bacteria of the order Burkholderiales are original environmental hosts of type II trimethoprim resistance genes (dfrB). It is consensus that clinically relevant antibiotic resistance genes have their origin in environmental bacteria, including the large pool of primarily benign species. Yet, for the vast majority of acquired antibiotic resistance genes, the original environmental host(s) has not been identified to date. Closing this knowledge gap could improve our understanding of how antimicrobial resistance proliferates in the bacterial domain and shed light on the crucial step of initial resistance gene mobilization in particular. Here, we combine information from publicly available long- and short-read environmental metagenomes as well as whole-genome sequences to identify the original environmental hosts of dfrB, a family of genes conferring resistance to trimethoprim. Although this gene family stands in the shadow of the more widespread, structurally different dfrA, it has recently gained attention through the discovery of several new members. Based on the genetic context of dfrB observed in long-read metagenomes, we predicted bacteria of the order Burkholderiales to function as original environmental hosts of the predominant gene variants in both soil and freshwater. The predictions were independently confirmed by whole-genome datasets and statistical correlations between dfrB abundance and taxonomic composition of environmental bacterial communities. Our study suggests that Burkholderiales in general and the family Comamonadaceae in particular represent environmental origins of dfrB genes, some of which now contribute to the acquired resistome of facultative pathogens. We propose that our workflow centered on long-read environmental metagenomes allows for the identification of the original hosts of further clinically relevant antibiotic resistance genes.202439658215
7429190.9998Industrial wastewater treatment plant enriches antibiotic resistance genes and alters the structure of microbial communities. Antibiotic resistance is an emerging global health crisis, driven largely by overuse and misuse of antibiotics. However, there are examples in which the production of these antimicrobial agents has polluted the environment with active antibiotic residues, selecting for antibiotic resistant bacteria and the genes they carry. In this work, we have used shotgun metagenomics to investigate the taxonomic structure and resistance gene composition of sludge communities in a treatment plant in Croatia receiving wastewater from production of the macrolide antibiotic azithromycin. We found that the total abundance of antibiotic resistance genes was three times higher in sludge from the treatment plant receiving wastewater from pharmaceutical production than in municipal sludge from a sewage treatment plant in Zagreb. Surprisingly, macrolide resistance genes did not have higher abundances in the industrial sludge, but genes associated with mobile genetic elements such as integrons had. We conclude that at high concentrations of antibiotics, selection may favor taxonomic shifts towards intrinsically resistant species or strains harboring chromosomal resistance mutations rather than acquisition of mobile resistance determinants. Our results underscore the need for regulatory action also within Europe to avoid release of antibiotics into the environment.201931301473