Clusters of Antibiotic Resistance Genes Enriched Together Stay Together in Swine Agriculture. - Related Documents




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388201.0000Clusters of Antibiotic Resistance Genes Enriched Together Stay Together in Swine Agriculture. Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk. IMPORTANCE: Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. As governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically.201627073098
405110.9999The 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.201021178459
399720.9999Pyrosequencing 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
388130.9999Meta-transcriptomics reveals a diverse antibiotic resistance gene pool in avian microbiomes. BACKGROUND: Antibiotic resistance is rendering common bacterial infections untreatable. Wildlife can incorporate and disperse antibiotic-resistant bacteria in the environment, such as water systems, which in turn serve as reservoirs of resistance genes for human pathogens. Anthropogenic activity may contribute to the spread of bacterial resistance cycling through natural environments, including through the release of human waste, as sewage treatment only partially removes antibiotic-resistant bacteria. However, empirical data supporting these effects are currently limited. Here we used bulk RNA-sequencing (meta-transcriptomics) to assess the diversity and expression levels of functionally viable resistance genes in the gut microbiome of birds with aquatic habits in diverse locations. RESULTS: We found antibiotic resistance genes in birds from all localities, from penguins in Antarctica to ducks in a wastewater treatment plant in Australia. Comparative analysis revealed that birds feeding at the wastewater treatment plant carried the greatest resistance gene burden, including genes typically associated with multidrug resistance plasmids as the aac(6)-Ib-cr gene. Differences in resistance gene burden also reflected aspects of bird ecology, taxonomy, and microbial function. Notably, ducks, which feed by dabbling, carried a higher abundance and diversity of resistance genes than turnstones, avocets, and penguins, which usually prey on more pristine waters. CONCLUSIONS: These transcriptome data suggest that human waste, even if it undergoes treatment, might contribute to the spread of antibiotic resistance genes to the wild. Differences in microbiome functioning across different bird lineages may also play a role in the antibiotic resistance burden carried by wild birds. In summary, we reveal the complex factors explaining the distribution of resistance genes and their exchange routes between humans and wildlife, and show that meta-transcriptomics is a valuable tool to access functional resistance genes in whole microbial communities.201930961590
769440.9999The Human Gut Resistome up to Extreme Longevity. Antibiotic resistance (AR) is indisputably a major health threat which has drawn much attention in recent years. In particular, the gut microbiome has been shown to act as a pool of AR genes, potentially available to be transferred to opportunistic pathogens. Herein, we investigated for the first time changes in the human gut resistome during aging, up to extreme longevity, by analyzing shotgun metagenomics data of fecal samples from a geographically defined cohort of 62 urban individuals, stratified into four age groups: young adults, elderly, centenarians, and semisupercentenarians, i.e., individuals aged up to 109 years. According to our findings, some AR genes are similarly represented in all subjects regardless of age, potentially forming part of the core resistome. Interestingly, aging was found to be associated with a higher burden of some AR genes, including especially proteobacterial genes encoding multidrug efflux pumps. Our results warn of possible health implications and pave the way for further investigations aimed at containing AR accumulation, with the ultimate goal of promoting healthy aging. IMPORTANCE Antibiotic resistance is widespread among different ecosystems, and in humans it plays a key role in shaping the composition of the gut microbiota, enhancing the ecological fitness of certain bacterial populations when exposed to antibiotics. A considerable component of the definition of healthy aging and longevity is associated with the structure of the gut microbiota, and, in this regard, the presence of antibiotic-resistant bacteria is critical to many pathologies that come about with aging. However, the structure of the resistome has not yet been sufficiently elucidated. Here, we show distinct antibiotic resistance assets and specific microbial consortia characterizing the human gut resistome through aging.202134494880
388450.9999Distribution and quantification of antibiotic resistant genes and bacteria across agricultural and non-agricultural metagenomes. There is concern that antibiotic resistance can potentially be transferred from animals to humans through the food chain. The relationship between specific antibiotic resistant bacteria and the genes they carry remains to be described. Few details are known about the ecology of antibiotic resistant genes and bacteria in food production systems, or how antibiotic resistance genes in food animals compare to antibiotic resistance genes in other ecosystems. Here we report the distribution of antibiotic resistant genes in publicly available agricultural and non-agricultural metagenomic samples and identify which bacteria are likely to be carrying those genes. Antibiotic resistance, as coded for in the genes used in this study, is a process that was associated with all natural, agricultural, and human-impacted ecosystems examined, with between 0.7 to 4.4% of all classified genes in each habitat coding for resistance to antibiotic and toxic compounds (RATC). Agricultural, human, and coastal-marine metagenomes have characteristic distributions of antibiotic resistance genes, and different bacteria that carry the genes. There is a larger percentage of the total genome associated with antibiotic resistance in gastrointestinal-associated and agricultural metagenomes compared to marine and Antarctic samples. Since antibiotic resistance genes are a natural part of both human-impacted and pristine habitats, presence of these resistance genes in any specific habitat is therefore not sufficient to indicate or determine impact of anthropogenic antibiotic use. We recommend that baseline studies and control samples be taken in order to determine natural background levels of antibiotic resistant bacteria and/or antibiotic resistance genes when investigating the impacts of veterinary use of antibiotics on human health. We raise questions regarding whether the underlying biology of each type of bacteria contributes to the likelihood of transfer via the food chain.201223133629
334260.9999Marine 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
334170.9999The 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
389380.9999Diverse antibiotic resistance genes in dairy cow manure. Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. IMPORTANCE The increasing prevalence of antibiotic resistance among bacteria is one of the most intractable challenges in 21st-century public health. The origins of resistance are complex, and a better understanding of the impacts of antibiotics used on farms would produce a more robust platform for public policy. Microbiomes of farm animals are reservoirs of antibiotic resistance genes, which may affect distribution of antibiotic resistance genes in human pathogens. Previous studies have focused on antibiotic resistance genes in manures of animals subjected to intensive antibiotic use, such as pigs and chickens. Cow manure has received less attention, although it is commonly used in crop production. Here, we report the discovery of novel and diverse antibiotic resistance genes in the cow microbiome, demonstrating that it is a significant reservoir of antibiotic resistance genes. The genomic resource presented here lays the groundwork for understanding the dispersal of antibiotic resistance from the agroecosystem to other settings.201424757214
334390.9999Shotgun 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
3894100.9999Novel 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
9653110.9999Evaluating the mobility potential of antibiotic resistance genes in environmental resistomes without metagenomics. Antibiotic resistance genes are ubiquitous in the environment. However, only a fraction of them are mobile and able to spread to pathogenic bacteria. Until now, studying the mobility of antibiotic resistance genes in environmental resistomes has been challenging due to inadequate sensitivity and difficulties in contig assembly of metagenome based methods. We developed a new cost and labor efficient method based on Inverse PCR and long read sequencing for studying mobility potential of environmental resistance genes. We applied Inverse PCR on sediment samples and identified 79 different MGE clusters associated with the studied resistance genes, including novel mobile genetic elements, co-selected resistance genes and a new putative antibiotic resistance gene. The results show that the method can be used in antibiotic resistance early warning systems. In comparison to metagenomics, Inverse PCR was markedly more sensitive and provided more data on resistance gene mobility and co-selected resistances.201627767072
4033120.9999Evolution 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.200717490428
9650130.9999Plasmid-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
3873140.9999Long-term exposure to antibiotics has caused accumulation of resistance determinants in the gut microbiota of honeybees. Antibiotic treatment can impact nontarget microbes, enriching the pool of resistance genes available to pathogens and altering community profiles of microbes beneficial to hosts. The gut microbiota of adult honeybees, a distinctive community dominated by eight bacterial species, provides an opportunity to examine evolutionary responses to long-term treatment with a single antibiotic. For decades, American beekeepers have routinely treated colonies with oxytetracycline for control of larval pathogens. Using a functional metagenomic screen of bacteria from Maryland bees, we detected a high incidence of tetracycline/oxytetracycline resistance. This resistance is attributable to known resistance loci for which nucleotide sequences and flanking mobility genes were nearly identical to those from human pathogens and from bacteria associated with farm animals. Surveys using diagnostic PCR and sequencing revealed that gut bacteria of honeybees from diverse localities in the United States harbor eight tetracycline resistance loci, including efflux pump genes (tetB, tetC, tetD, tetH, tetL, and tetY) and ribosome protection genes (tetM and tetW), often at high frequencies. Isolates of gut bacteria from Connecticut bees display high levels of tetracycline resistance. Resistance genes were ubiquitous in American samples, though rare in colonies unexposed for 25 years. In contrast, only three resistance loci, at low frequencies, occurred in samples from countries not using antibiotics in beekeeping and samples from wild bumblebees. Thus, long-term antibiotic treatment has caused the bee gut microbiota to accumulate resistance genes, drawn from a widespread pool of highly mobile loci characterized from pathogens and agricultural sites. We found that 50 years of using antibiotics in beekeeping in the United States has resulted in extensive tetracycline resistance in the gut microbiota. These bacteria, which form a distinctive community present in healthy honeybees worldwide, may function in protecting bees from disease and in providing nutrition. In countries that do not use antibiotics in beekeeping, bee gut bacteria contained far fewer resistance genes. The tetracycline resistance that we observed in American samples reflects the capture of mobile resistance genes closely related to those known from human pathogens and agricultural sites. Thus, long-term treatment to control a specific pathogen resulted in the accumulation of a stockpile of resistance capabilities in the microbiota of a healthy gut. This stockpile can, in turn, provide a source of resistance genes for pathogens themselves. The use of novel antibiotics in beekeeping may disrupt bee health, adding to the threats faced by these pollinators.201223111871
4127150.9998The Perfect Condition for the Rising of Superbugs: Person-to-Person Contact and Antibiotic Use Are the Key Factors Responsible for the Positive Correlation between Antibiotic Resistance Gene Diversity and Virulence Gene Diversity in Human Metagenomes. Human metagenomes with a high diversity of virulence genes tend to have a high diversity of antibiotic-resistance genes and vice-versa. To understand this positive correlation, we simulated the transfer of these genes and bacterial pathogens in a community of interacting people that take antibiotics when infected by pathogens. Simulations show that people with higher diversity of virulence and resistance genes took antibiotics long ago, not recently. On the other extreme, we find people with low diversity of both gene types because they took antibiotics recently-while antibiotics select specific resistance genes, they also decrease gene diversity by eliminating bacteria. In general, the diversity of virulence and resistance genes becomes positively correlated whenever the transmission probability between people is higher than the probability of losing resistance genes. The positive correlation holds even under changes of several variables, such as the relative or total diversity of virulence and resistance genes, the contamination probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the transmission between people and antibiotic usage are the leading causes for the positive correlation between virulence and antibiotic-resistance genes.202134065307
3830160.9998Resistance Gene Carriage Predicts Growth of Natural and Clinical Escherichia coli Isolates in the Absence of Antibiotics. Bacterial pathogens that carry antibiotic resistance alleles sometimes pay a cost in the form of impaired growth in antibiotic-free conditions. This cost of resistance is expected to be a key parameter for understanding how resistance spreads and persists in pathogen populations. Analysis of individual resistance alleles from laboratory evolution and natural isolates has shown they are typically costly, but these costs are highly variable and influenced by genetic variation at other loci. It therefore remains unclear how strongly resistance is linked to impaired antibiotic-free growth in bacteria from natural and clinical scenarios, where resistance alleles are likely to coincide with other types of genetic variation. To investigate this, we measured the growth of 92 natural and clinical Escherichia coli isolates across three antibiotic-free environments. We then tested whether variation of antibiotic-free growth among isolates was predicted by their resistance to 10 antibiotics, while accounting for the phylogenetic structure of the data. We found that isolates with similar resistance profiles had similar antibiotic-free growth profiles, but it was not simply that higher average resistance was associated with impaired growth. Next, we used whole-genome sequences to identify antibiotic resistance genes and found that isolates carrying a greater number of resistance gene types grew relatively poorly in antibiotic-free conditions, even when the resistance genes they carried were different. This suggests that the resistance of bacterial pathogens is linked to growth costs in nature, but it is the total genetic burden and multivariate resistance phenotype that predict these costs, rather than individual alleles or mean resistance across antibiotics.IMPORTANCE Managing the spread of antibiotic resistance in bacterial pathogens is a major challenge for global public health. Central to this challenge is understanding whether resistance is linked to impaired bacterial growth in the absence of antibiotics, because this determines whether resistance declines when bacteria are no longer exposed to antibiotics. We studied 92 isolates of the key bacterial pathogen Escherichia coli; these isolates varied in both their antibiotic resistance genes and other parts of the genome. Taking this approach, rather than focusing on individual genetic changes associated with resistance as in much previous work, revealed that growth without antibiotics was linked to the number of specialized resistance genes carried and the combination of antibiotics to which isolates were resistant but was not linked to average antibiotic resistance. This approach provides new insights into the genetic factors driving the long-term persistence of antibiotic-resistant bacteria, which is important for future efforts to predict and manage resistance.201930530714
9648170.9998The 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.202234856283
4049180.9998The Plasmidome of Firmicutes: Impact on the Emergence and the Spread of Resistance to Antimicrobials. The phylum Firmicutes is one of the most abundant groups of prokaryotes in the microbiota of humans and animals and includes genera of outstanding relevance in biomedicine, health care, and industry. Antimicrobial drug resistance is now considered a global health security challenge of the 21st century, and this heterogeneous group of microorganisms represents a significant part of this public health issue.The presence of the same resistant genes in unrelated bacterial genera indicates a complex history of genetic interactions. Plasmids have largely contributed to the spread of resistance genes among Staphylococcus, Enterococcus, and Streptococcus species, also influencing the selection and ecological variation of specific populations. However, this information is fragmented and often omits species outside these genera. To date, the antimicrobial resistance problem has been analyzed under a "single centric" perspective ("gene tracking" or "vehicle centric" in "single host-single pathogen" systems) that has greatly delayed the understanding of gene and plasmid dynamics and their role in the evolution of bacterial communities.This work analyzes the dynamics of antimicrobial resistance genes using gene exchange networks; the role of plasmids in the emergence, dissemination, and maintenance of genes encoding resistance to antimicrobials (antibiotics, heavy metals, and biocides); and their influence on the genomic diversity of the main Gram-positive opportunistic pathogens under the light of evolutionary ecology. A revision of the approaches to categorize plasmids in this group of microorganisms is given using the 1,326 fully sequenced plasmids of Gram-positive bacteria available in the GenBank database at the time the article was written.201526104702
4007190.9998Detecting horizontal gene transfer among microbiota: an innovative pipeline for identifying co-shared genes within the mobilome through advanced comparative analysis. Horizontal gene transfer (HGT) is a key driver in the evolution of bacterial genomes. The acquisition of genes mediated by HGT may enable bacteria to adapt to ever-changing environmental conditions. Long-term application of antibiotics in intensive agriculture is associated with the dissemination of antibiotic resistance genes among bacteria with the consequences causing public health concern. Commensal farm-animal-associated gut microbiota are considered the reservoir of the resistance genes. Therefore, in this study, we identified known and not-yet characterized mobilized genes originating from chicken and porcine fecal samples using our innovative pipeline followed by network analysis to provide appropriate visualization to support proper interpretation.202438099617