Mobile Genetic Elements Drive Antimicrobial Resistance Gene Spread in Pasteurellaceae Species. - Related Documents




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377501.0000Mobile Genetic Elements Drive Antimicrobial Resistance Gene Spread in Pasteurellaceae Species. Mobile genetic elements (MGEs) and antimicrobial resistance (AMR) drive important ecological relationships in microbial communities and pathogen-host interaction. In this study, we investigated the resistome-associated mobilome in 345 publicly available Pasteurellaceae genomes, a large family of Gram-negative bacteria including major human and animal pathogens. We generated a comprehensive dataset of the mobilome integrated into genomes, including 10,820 insertion sequences, 2,939 prophages, and 43 integrative and conjugative elements. Also, we assessed plasmid sequences of Pasteurellaceae. Our findings greatly expand the diversity of MGEs for the family, including a description of novel elements. We discovered that MGEs are comparable and dispersed across species and that they also co-occur in genomes, contributing to the family's ecology via gene transfer. In addition, we investigated the impact of these elements in the dissemination and shaping of AMR genes. A total of 55 different AMR genes were mapped to 721 locations in the dataset. MGEs are linked with 77.6% of AMR genes discovered, indicating their important involvement in the acquisition and transmission of such genes. This study provides an uncharted view of the Pasteurellaceae by demonstrating the global distribution of resistance genes linked with MGEs.202135069478
965010.9998Plasmid-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
334120.9998The 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
964930.9998Bacteria 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
377440.9998Forecasting the dissemination of antibiotic resistance genes across bacterial genomes. Antibiotic resistance spreads among bacteria through horizontal transfer of antibiotic resistance genes (ARGs). Here, we set out to determine predictive features of ARG transfer among bacterial clades. We use a statistical framework to identify putative horizontally transferred ARGs and the groups of bacteria that disseminate them. We identify 152 gene exchange networks containing 22,963 bacterial genomes. Analysis of ARG-surrounding sequences identify genes encoding putative mobilisation elements such as transposases and integrases that may be involved in gene transfer between genomes. Certain ARGs appear to be frequently mobilised by different mobile genetic elements. We characterise the phylogenetic reach of these mobilisation elements to predict the potential future dissemination of known ARGs. Using a separate database with 472,798 genomes from Streptococcaceae, Staphylococcaceae and Enterobacteriaceae, we confirm 34 of 94 predicted mobilisations. We explore transfer barriers beyond mobilisation and show experimentally that physiological constraints of the host can explain why specific genes are largely confined to Gram-negative bacteria although their mobile elements support dissemination to Gram-positive bacteria. Our approach may potentially enable better risk assessment of future resistance gene dissemination.202133893312
378450.9998Insight into the mobilome of Aeromonas strains. The mobilome is a pool of genes located within mobile genetic elements (MGE), such as plasmids, IS elements, transposons, genomic/pathogenicity islands, and integron-associated gene cassettes. These genes are often referred to as "flexible" and may encode virulence factors, toxic compounds as well as resistance to antibiotics. The phenomenon of MGE transfer between bacteria, known as horizontal gene transfer (HGT), is well documented. The genes present on MGE are subject to continuous processes of evolution and environmental changes, largely induced or significantly accelerated by man. For bacteria, the only chance of survival in an environment contaminated with toxic chemicals, heavy metals and antibiotics is the acquisition of genes providing the ability to survive in such conditions. The process of acquiring and spreading antibiotic resistance genes (ARG) is of particular significance, as it is important for the health of humans and animals. Therefore, it is important to thoroughly study the mobilome of Aeromonas spp. that is widely distributed in various environments, causing many diseases in fishes and humans. This review discusses the recently published information on MGE prevalent in Aeromonas spp. with special emphasis on plasmids belonging to different incompatibility groups, i.e., IncA/C, IncU, IncQ, IncF, IncI, and ColE-type. The vast majority of plasmids carry a number of different transposons (Tn3, Tn21, Tn1213, Tn1721, Tn4401), the 1st, 2nd, or 3rd class of integrons, IS elements (e.g., IS26, ISPa12, ISPa13, ISKpn8, ISKpn6) and encode determinants such as antibiotic and mercury resistance genes, as well as virulence factors. Although the actual role of Aeromonas spp. as a human pathogen remains controversial, species of this genus may pose a serious risk to human health. This is due to the considerable potential of their mobilome, particularly in terms of antibiotic resistance and the possibility of the horizontal transfer of resistance genes.201526074893
344960.9998Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide. OBJECTIVES: Antimicrobial-resistant bacteria are a major global health threat. Mobile genetic elements (MGEs) have been crucial for spreading resistance to new bacterial species, including human pathogens. Understanding how MGEs promote resistance could be essential for prevention. Here we present an investigation of MGEs and their association with resistance genes in pathogenic bacteria collected from 59 diagnostic units during 2020, representing a snapshot of clinical infections from 35 counties worldwide. METHODS: We analysed 3,095 whole-genome sequenced clinical bacterial isolates from over 100 species to study the relationship between resistance genes and MGEs. The mobiliome of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae were further examined for geographic differences, as these species were prevalent in all countries. Genes potentially mobilized by MGEs were identified by finding DNA segments containing MGEs and ARGs preserved in multiple species. Network analysis was used to investigate potential MGE interactions, host range, and transmission pathways. RESULTS: The prevalence and diversity of MGEs and resistance genes varied among species, with E. coli and S. aureus carrying more diverse elements. MGE composition differed between bacterial lineages, indicating strong vertical inheritance. 102 MGEs associated with resistance were found in multiple species, and four of these elements seemed to be highly transmissible as they were found in different phyla. We identified 21 genomic regions containing resistance genes potentially mobilized by MGEs, highlighting their importance in transmitting genes to clinically significant bacteria. CONCLUSION: Resistance genes are spread through various MGEs, including plasmids and transposons. Our findings suggest that multiple factors influence MGE prevalence and their transposability, thereby shaping the MGE population and transmission pathways. Some MGEs have a wider host range, which could make them more important for mobilizing genes. We also identified 103 resistance genes potentially mobilised by MGEs, which could increase their transmissibility to unrelated bacteria.202540824964
456070.9998High-resolution genomic surveillance elucidates a multilayered hierarchical transfer of resistance between WWTP- and human/animal-associated bacteria. BACKGROUND: Our interconnected world and the ability of bacteria to quickly swap antibiotic resistance genes (ARGs) make it particularly important to establish the epidemiological links of multidrug resistance (MDR) transfer between wastewater treatment plant (WWTP)- and human/animal-associated bacteria, under the One Health framework. However, evidence of ARGs exchange and potential factors that contribute to this transfer remain limited. RESULTS: Here, by combining culture-based population genomics and genetic comparisons with publicly available datasets, we reconstructed the complete genomes of 82 multidrug-resistant isolates from WWTPs and found that most WWTP-associated isolates were genetically distinct from their closest human/animal-associated relatives currently available in the public database. Even in the minority of lineages that were closely related, WWTP-associated isolates were characterized by quite different plasmid compositions. We identified a high diversity of circular plasmids (264 in total, of which 141 were potentially novel), which served as the main source of resistance, and showed potential horizontal transfer of ARG-bearing plasmids between WWTP- and humans/animal-associated bacteria. Notably, the potentially transferred ARGs and virulence factors (VFs) with different genetic backgrounds were closely associated with flanking insertion sequences (ISs), suggesting the importance of synergy between plasmids and ISs in mediating a multilayered hierarchical transfer of MDR and potentiating the emergence of MDR-hypervirulent clones. CONCLUSION: Our findings advance the current efforts to establish potential epidemiological links of MDR transmission between WWTP- and human/animal-associated bacteria. Plasmids play an important role in mediating the transfer of ARGs and the IS-associated ARGs that are carried by conjugative plasmids should be prioritized to tackle the spread of resistance. Video Abstract.202235078531
416080.9998The association between the genetic structures of commonly incompatible plasmids in Gram-negative bacteria, their distribution and the resistance genes. Incompatible plasmids play a crucial role in the horizontal transfer of antibiotic resistance in bacteria, particularly in Gram-negative bacteria, and have thus attracted considerable attention in the field of microbiological research. In the 1970s, these plasmids, housing an array of resistance genes and genetic elements, were predominantly discovered. They exhibit a broad presence in diverse host bacteria, showcasing diversity in geographic distribution and the spectrum of antibiotic resistance genes. The complex genetic structure of plasmids further accelerates the accumulation of resistance genes in Gram-negative bacteria. This article offers a comprehensive review encompassing the discovery process, host distribution, geographic prevalence, carried resistance genes, and the genetic structure of different types incompatible plasmids, including IncA, IncC, IncF, IncL, IncM, IncH, and IncP. It serves as a valuable reference for enhancing our understanding of the role of these different types of plasmids in bacterial evolution and the dissemination of antibiotic resistance.202439660283
378090.9998Is ICE hot? A genomic comparative study reveals integrative and conjugative elements as "hot" vectors for the dissemination of antibiotic resistance genes. Different from other extensively studied mobile genetic elements (MGEs) whose discoveries were initiated decades ago (1950s-1980s), integrative and conjugative elements (ICEs), a diverse array of more recently identified elements that were formally termed in 2002, have aroused increasing concern for their crucial contribution to the dissemination of antibiotic resistance genes (ARGs). However, the comprehensive understanding on ICEs' ARG profile across the bacterial tree of life is still blurred. Through a genomic study by comparison with two key MGEs, we, for the first time, systematically investigated the ARG profile as well as the host range of ICEs and also explored the MGE-specific potential to facilitate ARG propagation across phylogenetic barriers. These findings could serve as a theoretical foundation for risk assessment of ARGs mediated by distinct MGEs and further to optimize therapeutic strategies aimed at restraining antibiotic resistance crises.202338032189
4563100.9998Prophages as a source of antimicrobial resistance genes in the human microbiome. Prophages-viruses that integrate into bacterial genomes-are ubiquitous in the microbial realm. Prophages contribute significantly to horizontal gene transfer, including the potential spread of antimicrobial resistance (AMR) genes, because they can collect host genes. Understanding their role in the human microbiome is essential for fully understanding AMR dynamics and possible clinical implications. We analysed almost 15,000 bacterial genomes for prophages and AMR genes. The bacteria were isolated from diverse human body sites and geographical regions, and their genomes were retrieved from GenBank. AMR genes were detected in 6.6% of bacterial genomes, with a higher prevalence in people with symptomatic diseases. We found a wide variety of AMR genes combating multiple drug classes. We discovered AMR genes previously associated with plasmids, such as blaOXA-23 in Acinetobacter baumannii prophages or genes found in prophages in species they had not been previously described in, such as mefA-msrD in Gardnerella prophages, suggesting prophage-mediated gene transfer of AMR genes. Prophages encoding AMR genes were found at varying frequencies across body sites and geographical regions, with Asia showing the highest diversity of AMR genes.202540166311
3773110.9998Understanding the rapid spread of antimicrobial resistance genes mediated by IS26. Insertion sequences (ISs) promote the transmission of antimicrobial resistance genes (ARGs) across bacterial populations. However, their contributions and dynamics during the transmission of resistance remain unclear. In this study, we selected IS26 as a representative transposable element to decipher the relationship between ISs and ARGs and to investigate their transfer features and transmission trends. We retrieved 2656  translocatable  IS 26 -bounded  units with  ARGs (tIS26-bUs-ARGs) in complete bacterial genomes from the NCBI RefSeq database. In total, 124 ARGs spanning 12 classes of antibiotics were detected, and the average contribution rate of IS26 to these genes was 41.2%. We found that  IS 26 -bounded  units (IS26-bUs) mediated extensive ARG dissemination within the bacteria of the Gammaproteobacteria class, showing strong transfer potential between strains, species, and even phyla. The IS26-bUs expanded in bacterial populations over time, and their temporal expansion trend was significantly correlated with antibiotic usage. This wide dissemination could be due to the nonspecific target site preference of IS26. Finally, we experimentally confirmed that the introduction of a single copy of IS26 could lead to the formation of a composite transposon mediating the transmission of "passenger" genes. These observations extend our knowledge of the IS26 and provide new insights into the mediating role of ISs in the dissemination of antibiotic resistance.202438827508
3915120.9998Phylogenetic signature of lateral exchange of genes for antibiotic production and resistance among bacteria highlights a pattern of global transmission of pathogens between humans and livestock. The exchange of bacterial virulence factors driven by lateral gene transfer (LGT) can help indicate possible bacterial transmission among different hosts. Specifically, overlaying the phylogenetic signal of LGT among bacteria onto the distribution of respective isolation sources (hosts) can indicate patterns of transmission among these hosts. Here, we apply this approach towards a better understanding of patterns of bacterial transmission between humans and livestock. We utilize comparative genomics to trace patterns of LGT for an 11-gene operon responsible for the production of the antibiotic nisin and infer transmission of bacteria among respective host species. A total of 147 bacterial genomes obtained from NCBI were determined to contain the complete operon. Isolated from human, porcine and bovine hosts, these genomes represented six Streptococcus and one Staphylococcus species. Phylogenetic analyses of the operon sequences revealed a signature of frequent and recent lateral gene transfer that indicated extensive bacterial transmission between humans and pigs. For 11 isolates, we detected a Tn916-like transposon inserted into the operon. The transposon contained the tetM gene (tetracycline resistance) and additional phylogenetic analyses indicated transmission among human and animal hosts. The bacteria possessing the nisin operon and transposon were isolated from hosts distributed globally. These findings possibly reflect both the globalization of the food industry and an increasingly mobile and expanding human population. In addition to concerns regarding zoonosis, these findings also highlight the potential threat to livestock worldwide due to reverse zoonosis.201829631053
3342130.9997Marine 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
4666140.9997Large Circular Plasmids from Groundwater Plasmidomes Span Multiple Incompatibility Groups and Are Enriched in Multimetal Resistance Genes. Naturally occurring plasmids constitute a major category of mobile genetic elements responsible for harboring and transferring genes important in survival and fitness. A targeted evaluation of plasmidomes can reveal unique adaptations required by microbial communities. We developed a model system to optimize plasmid DNA isolation procedures targeted to groundwater samples which are typically characterized by low cell density (and likely variations in the plasmid size and copy numbers). The optimized method resulted in successful identification of several hundred circular plasmids, including some large plasmids (11 plasmids more than 50 kb in size, with the largest being 1.7 Mb in size). Several interesting observations were made from the analysis of plasmid DNA isolated in this study. The plasmid pool (plasmidome) was more conserved than the corresponding microbiome distribution (16S rRNA based). The circular plasmids were diverse as represented by the presence of seven plasmid incompatibility groups. The genes carried on these groundwater plasmids were highly enriched in metal resistance. Results from this study confirmed that traits such as metal, antibiotic, and phage resistance along with toxin-antitoxin systems are encoded on abundant circular plasmids, all of which could confer novel and advantageous traits to their hosts. This study confirms the ecological role of the plasmidome in maintaining the latent capacity of a microbiome, enabling rapid adaptation to environmental stresses.IMPORTANCE Plasmidomes have been typically studied in environments abundant in bacteria, and this is the first study to explore plasmids from an environment characterized by low cell density. We specifically target groundwater, a significant source of water for human/agriculture use. We used samples from a well-studied site and identified hundreds of circular plasmids, including one of the largest sizes reported in plasmidome studies. The striking similarity of the plasmid-borne ORFs in terms of taxonomical and functional classifications across several samples suggests a conserved plasmid pool, in contrast to the observed variability in the 16S rRNA-based microbiome distribution. Additionally, the stress response to environmental factors has stronger conservation via plasmid-borne genes as marked by abundance of metal resistance genes. Last, identification of novel and diverse plasmids enriches the existing plasmid database(s) and serves as a paradigm to increase the repertoire of biological parts that are available for modifying novel environmental strains.201930808697
3440150.9997Global dissemination of the beta-lactam resistance gene blaTEM-1 among pathogenic bacteria. Antibiotic resistance presents a burgeoning global health crisis, with over 70 % of pathogenic bacteria now exhibiting resistance to at least one antibiotic. This study leverages a vast dataset of 618,853 pathogenic bacterial genomes from the NCBI pathogen detection database, offering comprehensive insights into antibiotic resistance patterns, species-specific profiles, and transmission dynamics of resistant pathogens. We centered our investigation on the beta-lactam resistance gene blaTEM-1, found in 43,339 genomes, revealing its extensive distribution across diverse species and isolation sources. The study unveiled the prevalence of 15 prominent antibiotic resistance genes (ARGs), including those conferring resistance to beta-lactam, aminoglycoside, and tetracycline antibiotics. Distinct resistance patterns were observed between Gram-positive and Gram-negative bacteria, indicating the influence of phylogeny on resistance dissemination. Notably, the blaTEM-1 gene demonstrated substantial prevalence across a wide array of bacterial species (8) and a high number of isolation sources (11). Genetic context analysis revealed associations between blaTEM-1 and mobile genetic elements (MGEs) like transposons and insertion sequences. Additionally, we observed recent horizontal transfer events involving clusters of blaTEM-1 genes and MGEs underscore the potential of MGEs in facilitating the mobilization of ARGs. Our findings underscore the importance of adopting a One Health approach to global genomic pathogen surveillance, aiming to uncover the transmission routes of ARGs and formulate strategies to address the escalating antibiotic resistance crisis.202539824112
9654160.9997Studying the Association between Antibiotic Resistance Genes and Insertion Sequences in Metagenomes: Challenges and Pitfalls. Antibiotic resistance is an issue in many areas of human activity. The mobilization of antibiotic resistance genes within the bacterial community makes it difficult to study and control the phenomenon. It is known that certain insertion sequences, which are mobile genetic elements, can participate in the mobilization of antibiotic resistance genes and in the expression of these genes. However, the magnitude of the contribution of insertion sequences to the mobility of antibiotic resistance genes remains understudied. In this study, the relationships between insertion sequences and antibiotic resistance genes present in the microbiome were investigated using two public datasets. The first made it possible to analyze the effects of different antibiotics in a controlled mouse model. The second dataset came from a study of the differences between conventional and organic-raised cattle. Although it was possible to find statistically significant correlations between the insertion sequences and antibiotic resistance genes in both datasets, several challenges remain to better understand the contribution of insertion sequences to the motility of antibiotic resistance genes. Obtaining more complete and less fragmented metagenomes with long-read sequencing technologies could make it possible to understand the mechanisms favoring horizontal transfers within the microbiome with greater precision.202336671375
3251170.9997Coexistence of Antibiotic Resistance Genes and Virulence Factors Deciphered by Large-Scale Complete Genome Analysis. Widespread use of antibiotics has enhanced the evolution of highly resilient pathogens and poses a severe risk to human health via coselection of antibiotic resistance genes (ARGs) and virulence factors (VFs). In this study, we rigorously evaluate the abundance relationship and physical linkage between ARGs and VFs by performing a comprehensive analysis of 9,070 bacterial genomes isolated from multiple species and hosts. The coexistence of ARGs and VFs was observed in bacteria across distinct phyla, pathogenicities, and habitats, especially among human-associated pathogens. The coexistence patterns of gene elements in different habitats and pathogenicity groups were similar, presumably due to frequent gene transfer. A shorter intergenic distance between mobile genetic elements and ARGs/VFs was detected in human/animal-associated bacteria, indicating a higher transfer potential. Increased accumulation of exogenous ARGs/VFs in human pathogens highlights the importance of gene acquisition in the evolution of human commensal bacteria. Overall, the findings provide insights into the genic features of combinations of ARG-VF and expand our understanding of ARG-VF coexistence in bacteria.IMPORTANCE Antibiotic resistance has become a serious global health concern. Despite numerous case studies, a comprehensive analysis of ARG and VF coexistence in bacteria is lacking. In this study, we explore the coexistence profiles of ARGs and VFs in diverse categories of bacteria by using a high-resolution bioinformatics approach. We also provide compelling evidence of unique ARG-VF gene pairs coexisting in specific bacterial genomes and reveal the potential risk associated with the coexistence of ARGs and VFs in organisms in both clinical settings and environments.202032487745
3894180.9997Novel Soil-Derived Beta-Lactam, Chloramphenicol, Fosfomycin and Trimethoprim Resistance Genes Revealed by Functional Metagenomics. Antibiotic resistance genes (ARGs) in soil are considered to represent one of the largest environmental resistomes on our planet. As these genes can potentially be disseminated among microorganisms via horizontal gene transfer (HGT) and in some cases are acquired by clinical pathogens, knowledge about their diversity, mobility and encoded resistance spectra gained increasing public attention. This knowledge offers opportunities with respect to improved risk prediction and development of strategies to tackle antibiotic resistance, and might help to direct the design of novel antibiotics, before further resistances reach hospital settings or the animal sector. Here, metagenomic libraries, which comprise genes of cultivated microorganisms, but, importantly, also those carried by the uncultured microbial majority, were screened for novel ARGs from forest and grassland soils. We detected three new beta-lactam, a so far unknown chloramphenicol, a novel fosfomycin, as well as three previously undiscovered trimethoprim resistance genes. These ARGs were derived from phylogenetically diverse soil bacteria and predicted to encode antibiotic inactivation, antibiotic efflux, or alternative variants of target enzymes. Moreover, deduced gene products show a minimum identity of ~21% to reference database entries and confer high-level resistance. This highlights the vast potential of functional metagenomics for the discovery of novel ARGs from soil ecosystems.202133916668
4665190.9997A comprehensive survey of integron-associated genes present in metagenomes. BACKGROUND: Integrons are genomic elements that mediate horizontal gene transfer by inserting and removing genetic material using site-specific recombination. Integrons are commonly found in bacterial genomes, where they maintain a large and diverse set of genes that plays an important role in adaptation and evolution. Previous studies have started to characterize the wide range of biological functions present in integrons. However, the efforts have so far mainly been limited to genomes from cultivable bacteria and amplicons generated by PCR, thus targeting only a small part of the total integron diversity. Metagenomic data, generated by direct sequencing of environmental and clinical samples, provides a more holistic and unbiased analysis of integron-associated genes. However, the fragmented nature of metagenomic data has previously made such analysis highly challenging. RESULTS: Here, we present a systematic survey of integron-associated genes in metagenomic data. The analysis was based on a newly developed computational method where integron-associated genes were identified by detecting their associated recombination sites. By processing contiguous sequences assembled from more than 10 terabases of metagenomic data, we were able to identify 13,397 unique integron-associated genes. Metagenomes from marine microbial communities had the highest occurrence of integron-associated genes with levels more than 100-fold higher than in the human microbiome. The identified genes had a large functional diversity spanning over several functional classes. Genes associated with defense mechanisms and mobility facilitators were most overrepresented and more than five times as common in integrons compared to other bacterial genes. As many as two thirds of the genes were found to encode proteins of unknown function. Less than 1% of the genes were associated with antibiotic resistance, of which several were novel, previously undescribed, resistance gene variants. CONCLUSIONS: Our results highlight the large functional diversity maintained by integrons present in unculturable bacteria and significantly expands the number of described integron-associated genes.202032689930