# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9660 | 0 | 1.0000 | Interkingdom Gut Microbiome and Resistome of the Cockroach Blattella germanica. Cockroaches are intriguing animals with two coexisting symbiotic systems, an endosymbiont in the fat body, involved in nitrogen metabolism, and a gut microbiome whose diversity, complexity, role, and developmental dynamics have not been fully elucidated. In this work, we present a metagenomic approach to study Blattella germanica populations not treated, treated with kanamycin, and recovered after treatment, both naturally and by adding feces to the diet, with the aim of better understanding the structure and function of its gut microbiome along the development as well as the characterization of its resistome.IMPORTANCE For the first time, we analyze the interkingdom hindgut microbiome of this species, including bacteria, fungi, archaea, and viruses. Network analysis reveals putative cooperation between core bacteria that could be key for ecosystem equilibrium. We also show how antibiotic treatments alter microbiota diversity and function, while both features are restored after one untreated generation. Combining data from B. germanica treated with three antibiotics, we have characterized this species' resistome. It includes genes involved in resistance to several broad-spectrum antibiotics frequently used in the clinic. The presence of genetic elements involved in DNA mobilization indicates that they can be transferred among microbiota partners. Therefore, cockroaches can be considered reservoirs of antibiotic resistance genes (ARGs) and potential transmission vectors. | 2021 | 33975971 |
| 9659 | 1 | 0.9999 | Phylogenetic barriers to horizontal transfer of antimicrobial peptide resistance genes in the human gut microbiota. The human gut microbiota has adapted to the presence of antimicrobial peptides (AMPs), which are ancient components of immune defence. Despite its medical importance, it has remained unclear whether AMP resistance genes in the gut microbiome are available for genetic exchange between bacterial species. Here, we show that AMP resistance and antibiotic resistance genes differ in their mobilization patterns and functional compatibilities with new bacterial hosts. First, whereas AMP resistance genes are widespread in the gut microbiome, their rate of horizontal transfer is lower than that of antibiotic resistance genes. Second, gut microbiota culturing and functional metagenomics have revealed that AMP resistance genes originating from phylogenetically distant bacteria have only a limited potential to confer resistance in Escherichia coli, an intrinsically susceptible species. Taken together, functional compatibility with the new bacterial host emerges as a key factor limiting the genetic exchange of AMP resistance genes. Finally, our results suggest that AMPs induce highly specific changes in the composition of the human microbiota, with implications for disease risks. | 2019 | 30559406 |
| 3997 | 2 | 0.9999 | Pyrosequencing 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. | 2011 | 21359229 |
| 4034 | 3 | 0.9999 | Environmental and clinical antibiotic resistomes, same only different. The history of antibiotic use in the clinic is one of initial efficacy followed inevitably by the emergence of resistance. Often this resistance is the result of the capture and mobilization of genes that have their origins in environmental reservoirs. Both antibiotic production and resistance are ancient and widely distributed among microbes in the environment. This deep reservoir of resistance offers the opportunity for gene flow into susceptible disease-causing bacteria. Not all resistance genes are equally successfully mobilized, and some dominate in the clinic. The differences and similarities in resistance mechanisms and associated genes among environments reveal a complex interplay between gene capture and mobilization that requires study of gene diversity and gene product function to fully understand the breadth and depth of resistance and the risk to human health. | 2019 | 31330416 |
| 4052 | 4 | 0.9998 | Functional metagenomics for the investigation of antibiotic resistance. Antibiotic resistance is a major threat to human health and well-being. To effectively combat this problem we need to understand the range of different resistance genes that allow bacteria to resist antibiotics. To do this the whole microbiota needs to be investigated. As most bacteria cannot be cultivated in the laboratory, the reservoir of antibiotic resistance genes in the non-cultivatable majority remains relatively unexplored. Currently the only way to study antibiotic resistance in these organisms is to use metagenomic approaches. Furthermore, the only method that does not require any prior knowledge about the resistance genes is functional metagenomics, which involves expressing genes from metagenomic clones in surrogate hosts. In this review the methods and limitations of functional metagenomics to isolate new antibiotic resistance genes and the mobile genetic elements that mediate their spread are explored. | 2014 | 24556726 |
| 9654 | 5 | 0.9998 | Studying 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. | 2023 | 36671375 |
| 4033 | 6 | 0.9998 | Evolution and ecology of antibiotic resistance genes. A new perspective on the topic of antibiotic resistance is beginning to emerge based on a broader evolutionary and ecological understanding rather than from the traditional boundaries of clinical research of antibiotic-resistant bacterial pathogens. Phylogenetic insights into the evolution and diversity of several antibiotic resistance genes suggest that at least some of these genes have a long evolutionary history of diversification that began well before the 'antibiotic era'. Besides, there is no indication that lateral gene transfer from antibiotic-producing bacteria has played any significant role in shaping the pool of antibiotic resistance genes in clinically relevant and commensal bacteria. Most likely, the primary antibiotic resistance gene pool originated and diversified within the environmental bacterial communities, from which the genes were mobilized and penetrated into taxonomically and ecologically distant bacterial populations, including pathogens. Dissemination and penetration of antibiotic resistance genes from antibiotic producers were less significant and essentially limited to other high G+C bacteria. Besides direct selection by antibiotics, there is a number of other factors that may contribute to dissemination and maintenance of antibiotic resistance genes in bacterial populations. | 2007 | 17490428 |
| 9651 | 7 | 0.9998 | Host- plasmid network structure in wastewater is linked to antimicrobial resistance genes. As mobile genetic elements, plasmids are central for our understanding of antimicrobial resistance spread in microbial communities. Plasmids can have varying fitness effects on their host bacteria, which will markedly impact their role as antimicrobial resistance vectors. Using a plasmid population model, we first show that beneficial plasmids interact with a higher number of hosts than costly plasmids when embedded in a community with multiple hosts and plasmids. We then analyse the network of a natural host-plasmid wastewater community from a Hi-C metagenomics dataset. As predicted by the model, we find that antimicrobial resistance encoding plasmids, which are likely to have positive fitness effects on their hosts in wastewater, interact with more bacterial taxa than non-antimicrobial resistance plasmids and are disproportionally important for connecting the entire network compared to non- antimicrobial resistance plasmids. This highlights the role of antimicrobials in restructuring host-plasmid networks by increasing the benefits of antimicrobial resistance carrying plasmids, which can have consequences for the spread of antimicrobial resistance genes through microbial networks. Furthermore, that antimicrobial resistance encoding plasmids are associated with a broader range of hosts implies that they will be more robust to turnover of bacterial strains. | 2024 | 38228585 |
| 4036 | 8 | 0.9998 | Man-made microbial resistances in built environments. Antimicrobial resistance is a serious threat to global public health, but little is known about the effects of microbial control on the microbiota and its associated resistome. Here we compare the microbiota present on surfaces of clinical settings with other built environments. Using state-of-the-art metagenomics approaches and genome and plasmid reconstruction, we show that increased confinement and cleaning is associated with a loss of microbial diversity and a shift from Gram-positive bacteria, such as Actinobacteria and Firmicutes, to Gram-negative such as Proteobacteria. Moreover, the microbiome of highly maintained built environments has a different resistome when compared to other built environments, as well as a higher diversity in resistance genes. Our results highlight that the loss of microbial diversity correlates with an increase in resistance, and the need for implementing strategies to restore bacterial diversity in certain built environments. | 2019 | 30814504 |
| 9649 | 9 | 0.9998 | Bacteria 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. | 2024 | 39658215 |
| 9648 | 10 | 0.9998 | The highly diverse Antarctic Peninsula soil microbiota as a source of novel resistance genes. The rise of multiresistant bacterial pathogens is currently one of the most critical threats to global health, encouraging a better understanding of the evolution and spread of antimicrobial resistance. In this regard, the role of the environment as a source of resistance mechanisms remains poorly understood. Moreover, we still know a minimal part of the microbial diversity and resistome present in remote and extreme environments, hosting microbes that evolved to resist harsh conditions and thus a potentially rich source of novel resistance genes. This work demonstrated that the Antarctic Peninsula soils host a remarkable microbial diversity and a widespread presence of autochthonous antibiotic-resistant bacteria and resistance genes. We observed resistance to a wide array of antibiotics among isolates, including Pseudomonas resisting ten or more different compounds, with an overall increased resistance in bacteria from non-intervened areas. In addition, genome analysis of selected isolates showed several genes encoding efflux pumps, as well as a lack of known resistance genes for some of the resisted antibiotics, including colistin, suggesting novel uncharacterized mechanisms. By combining metagenomic approaches based on analyzing raw reads, assembled contigs, and metagenome-assembled genomes, we found hundreds of widely distributed genes potentially conferring resistance to different antibiotics (including an outstanding variety of inactivation enzymes), metals, and biocides, hosted mainly by Polaromonas, Pseudomonas, Streptomyces, Variovorax, and Burkholderia. Furthermore, a proportion of these genes were found inside predicted plasmids and other mobile elements, including a putative OXA-like carbapenemase from Polaromonas harboring conserved key residues and predicted structural features. All this evidence indicates that the Antarctic Peninsula soil microbiota has a broad natural resistome, part of which could be transferred horizontally to pathogenic bacteria, acting as a potential source of novel resistance genes. | 2022 | 34856283 |
| 9657 | 11 | 0.9998 | Machine Learning Leveraging Genomes from Metagenomes Identifies Influential Antibiotic Resistance Genes in the Infant Gut Microbiome. Antibiotic resistance in pathogens is extensively studied, and yet little is known about how antibiotic resistance genes of typical gut bacteria influence microbiome dynamics. Here, we leveraged genomes from metagenomes to investigate how genes of the premature infant gut resistome correspond to the ability of bacteria to survive under certain environmental and clinical conditions. We found that formula feeding impacts the resistome. Random forest models corroborated by statistical tests revealed that the gut resistome of formula-fed infants is enriched in class D beta-lactamase genes. Interestingly, Clostridium difficile strains harboring this gene are at higher abundance in formula-fed infants than C. difficile strains lacking this gene. Organisms with genes for major facilitator superfamily drug efflux pumps have higher replication rates under all conditions, even in the absence of antibiotic therapy. Using a machine learning approach, we identified genes that are predictive of an organism's direction of change in relative abundance after administration of vancomycin and cephalosporin antibiotics. The most accurate results were obtained by reducing annotated genomic data to five principal components classified by boosted decision trees. Among the genes involved in predicting whether an organism increased in relative abundance after treatment are those that encode subclass B2 beta-lactamases and transcriptional regulators of vancomycin resistance. This demonstrates that machine learning applied to genome-resolved metagenomics data can identify key genes for survival after antibiotics treatment and predict how organisms in the gut microbiome will respond to antibiotic administration. IMPORTANCE The process of reconstructing genomes from environmental sequence data (genome-resolved metagenomics) allows unique insight into microbial systems. We apply this technique to investigate how the antibiotic resistance genes of bacteria affect their ability to flourish in the gut under various conditions. Our analysis reveals that strain-level selection in formula-fed infants drives enrichment of beta-lactamase genes in the gut resistome. Using genomes from metagenomes, we built a machine learning model to predict how organisms in the gut microbial community respond to perturbation by antibiotics. This may eventually have clinical applications. | 2018 | 29359195 |
| 4051 | 12 | 0.9998 | The human microbiome harbors a diverse reservoir of antibiotic resistance genes. The increasing levels of multi-drug resistance in human pathogenic bacteria are compromising our ability to treat infectious disease. Since antibiotic resistance determinants are readily exchanged between bacteria through lateral gene transfer, there is an increasing interest in investigating reservoirs of antibiotic resistance accessible to pathogens. Due to the high likelihood of contact and genetic exchange with pathogens during disease progression, the human microflora warrants special attention as perhaps the most accessible reservoir of resistance genes. Indeed, numerous previous studies have demonstrated substantial antibiotic resistance in cultured isolates from the human microflora. By applying metagenomic functional selections, we recently demonstrated that the functional repertoire of resistance genes in the human microbiome is much more diverse than suggested using previous culture-dependent methods. We showed that many resistance genes from cultured proteobacteria from human fecal samples are identical to resistance genes harbored by human pathogens, providing strong support for recent genetic exchange of this resistance machinery. In contrast, most of the resistance genes we identified with culture independent metagenomic sampling from the same samples were novel when compared to all known genes in public databases. While this clearly demonstrates that the antibiotic resistance reservoir of the large fraction of the human microbiome recalcitrant to culturing is severely under sampled, it may also suggest that barriers exist to lateral gene transfer between these bacteria and readily cultured human pathogens. If we hope to turn the tide against multidrug resistant infections, we must urgently commit to quantitatively characterizing the resistance reservoirs encoded by our diverse human microbiomes, with a particular focus on routes of exchange of these reservoirs with other microbial communities. | 2010 | 21178459 |
| 9658 | 13 | 0.9998 | Functional metagenomic libraries generated from anthropogenically impacted environments reveal importance of metabolic genes in biocide and antibiotic resistance. Anthropogenic activities result in the release of antimicrobial resistant bacteria and a cocktail of antimicrobial compounds into the environment that may directly select or indirectly co-select for antimicrobial resistance (AMR). Many studies use metagenome sequencing or qPCR-based approaches to study the environmental resistome but these methods are limited by a priori knowledge. In this study, a functional metagenomic approach was used to explore biocide resistance mechanisms in two contaminated environments and a pristine site, and to identify whether potentially novel genes conferring biocide resistance also conferred resistance or reduced susceptibility to antibiotics. Resistance was predominately mediated through novel mechanisms exclusive of the well-known qac efflux genes. UDP-galactose 4-epimerase (galE) -like genes were identified in both contaminated environments and were shown to confer cross-resistance to biocides and clinically important antibiotics for the first time (to our knowledge), compared to knockout mutants. GalE -like genes were also co-located with transposons, suggesting mobilisation potential. These results show that housekeeping genes may play a significant yet underappreciated role in AMR in environmental microbiomes. | 2023 | 36908773 |
| 9647 | 14 | 0.9998 | Dissemination of antibiotic resistance genes from antibiotic producers to pathogens. It has been hypothesized that some antibiotic resistance genes (ARGs) found in pathogenic bacteria derive from antibiotic-producing actinobacteria. Here we provide bioinformatic and experimental evidence supporting this hypothesis. We identify genes in proteobacteria, including some pathogens, that appear to be closely related to actinobacterial ARGs known to confer resistance against clinically important antibiotics. Furthermore, we identify two potential examples of recent horizontal transfer of actinobacterial ARGs to proteobacterial pathogens. Based on this bioinformatic evidence, we propose and experimentally test a 'carry-back' mechanism for the transfer, involving conjugative transfer of a carrier sequence from proteobacteria to actinobacteria, recombination of the carrier sequence with the actinobacterial ARG, followed by natural transformation of proteobacteria with the carrier-sandwiched ARG. Our results support the existence of ancient and, possibly, recent transfers of ARGs from antibiotic-producing actinobacteria to proteobacteria, and provide evidence for a defined mechanism. | 2017 | 28589945 |
| 9695 | 15 | 0.9998 | Antibiotic resistance with particular reference to soil microorganisms. Evidence of increasing resistance to antibiotics in soil and other natural isolates highlights the importance of horizontal transfer of resistance genes in facilitating gene flux in bacteria. Horizontal gene transfer in bacteria is favored by the presence of mobile genetic elements and by the organization of bacterial genomes into operons allowing for the cooperative transfer of genes with related functions. The selective pressure for the spread of resistance genes correlates strongly with the clinical and agricultural overuse of antibiotics. The future of antimicrobial chemotherapy may lie in developing new antimicrobials using information from comparative functional microbial genomics to find genetic targets for antimicrobials and also to understand gene expression enabling selective targeting of genes with expression that correlates with the infectious process. | 2001 | 11446510 |
| 3880 | 16 | 0.9998 | Extensively acquired antimicrobial-resistant bacteria restructure the individual microbial community in post-antibiotic conditions. In recent years, the overuse of antibiotics has led to the emergence of antimicrobial-resistant (AMR) bacteria. To evaluate the spread of AMR bacteria, the reservoir of AMR genes (resistome) has been identified in environmental samples, hospital environments, and human populations, but the functional role of AMR bacteria and their persistence within individuals has not been fully investigated. Here, we performed a strain-resolved in-depth analysis of the resistome changes by reconstructing a large number of metagenome-assembled genomes from the gut microbiome of an antibiotic-treated individual. Interestingly, we identified two bacterial populations with different resistome profiles: extensively acquired antimicrobial-resistant bacteria (EARB) and sporadically acquired antimicrobial-resistant bacteria, and found that EARB showed broader drug resistance and a significant functional role in shaping individual microbiome composition after antibiotic treatment. Our findings of AMR bacteria would provide a new avenue for controlling the spread of AMR bacteria in the human community. | 2025 | 40360555 |
| 4025 | 17 | 0.9998 | Metagenomic Insights into Transferable Antibiotic Resistance in Oral Bacteria. Antibiotic resistance is considered one of the greatest threats to global public health. Resistance is often conferred by the presence of antibiotic resistance genes (ARGs), which are readily found in the oral microbiome. In-depth genetic analyses of the oral microbiome through metagenomic techniques reveal a broad distribution of ARGs (including novel ARGs) in individuals not recently exposed to antibiotics, including humans in isolated indigenous populations. This has resulted in a paradigm shift from focusing on the carriage of antibiotic resistance in pathogenic bacteria to a broader concept of an oral resistome, which includes all resistance genes in the microbiome. Metagenomics is beginning to demonstrate the role of the oral resistome and horizontal gene transfer within and between commensals in the absence of selective pressure, such as an antibiotic. At the chairside, metagenomic data reinforce our need to adhere to current antibiotic guidelines to minimize the spread of resistance, as such data reveal the extent of ARGs without exposure to antimicrobials and the ecologic changes created in the oral microbiome by even a single dose of antibiotics. The aim of this review is to discuss the role of metagenomics in the investigation of the oral resistome, including the transmission of antibiotic resistance in the oral microbiome. Future perspectives, including clinical implications of the findings from metagenomic investigations of oral ARGs, are also considered. | 2016 | 27183895 |
| 4050 | 18 | 0.9998 | Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids. Although pathogenic bacteria are the targets of antibiotics, these drugs also affect hundreds of commensal or mutualistic species. Moreover, the use of antibiotics is not only restricted to the treatment of infections but is also largely applied in agriculture and in prophylaxis. During this work, we tested the hypothesis that there is a correlation between the number and the genomic location of antibiotic resistance (AR) genes and virulence factor (VF) genes. We performed a comprehensive study of 16,632 reference bacterial genomes in which we identified and counted all orthologues of AR and VF genes in each of the locations: chromosomes, plasmids, or in both locations of the same genome. We found that, on a global scale, no correlation emerges. However, some categories of AR and VF genes co-occur preferentially, and in the mobilome, which supports the hypothesis that some bacterial pathogens are under selective pressure to be resistant to specific antibiotics, a fact that can jeopardize antimicrobial therapy for some human-threatening diseases. | 2022 | 35740113 |
| 4102 | 19 | 0.9998 | Forces shaping the antibiotic resistome. Antibiotic resistance has become a problem of global scale. Resistance arises through mutation or through the acquisition of resistance gene(s) from other bacteria in a process called horizontal gene transfer (HGT). While HGT is recognized as an important factor in the dissemination of resistance genes in clinical pathogens, its role in the environment has been called into question by a recent study published in Nature. The authors found little evidence of HGT in soil using a culture-independent functional metagenomics approach, which is in contrast to previous work from the same lab showing HGT between the environment and human microbiome. While surprising at face value, these results may be explained by the lack of selective pressure in the environment studied. Importantly, this work suggests the need for careful monitoring of environmental antibiotic pollution and stringent antibiotic stewardship in the fight against resistance. | 2014 | 25213620 |