# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4652 | 0 | 1.0000 | Antibiotic-resistant soil bacteria in transgenic plant fields. Understanding the prevalence and polymorphism of antibiotic resistance genes in soil bacteria and their potential to be transferred horizontally is required to evaluate the likelihood and ecological (and possibly clinical) consequences of the transfer of these genes from transgenic plants to soil bacteria. In this study, we combined culture-dependent and -independent approaches to study the prevalence and diversity of bla genes in soil bacteria and the potential impact that a 10-successive-year culture of the transgenic Bt176 corn, which has a blaTEM marker gene, could have had on the soil bacterial community. The bla gene encoding resistance to ampicillin belongs to the beta-lactam antibiotic family, which is widely used in medicine but is readily compromised by bacterial antibiotic resistance. Our results indicate that soil bacteria are naturally resistant to a broad spectrum of beta-lactam antibiotics, including the third cephalosporin generation, which has a slightly stronger discriminating effect on soil isolates than other cephalosporins. These high resistance levels for a wide range of antibiotics are partly due to the polymorphism of bla genes, which occur frequently among soil bacteria. The blaTEM116 gene of the transgenic corn Bt176 investigated here is among those frequently found, thus reducing any risk of introducing a new bacterial resistance trait from the transgenic material. In addition, no significant differences were observed in bacterial antibiotic-resistance levels between transgenic and nontransgenic corn fields, although the bacterial populations were different. | 2008 | 18292221 |
| 9655 | 1 | 0.9999 | High genomic diversity of multi-drug resistant wastewater Escherichia coli. Wastewater treatment plants play an important role in the emergence of antibiotic resistance. They provide a hot spot for exchange of resistance within and between species. Here, we analyse and quantify the genomic diversity of the indicator Escherichia coli in a German wastewater treatment plant and we relate it to isolates' antibiotic resistance. Our results show a surprisingly large pan-genome, which mirrors how rich an environment a treatment plant is. We link the genomic analysis to a phenotypic resistance screen and pinpoint genomic hot spots, which correlate with a resistance phenotype. Besides well-known resistance genes, this forward genomics approach generates many novel genes, which correlated with resistance and which are partly completely unknown. A surprising overall finding of our analyses is that we do not see any difference in resistance and pan genome size between isolates taken from the inflow of the treatment plant and from the outflow. This means that while treatment plants reduce the amount of bacteria released into the environment, they do not reduce the potential for antibiotic resistance of these bacteria. | 2018 | 29895899 |
| 4651 | 2 | 0.9999 | Long-term shifts in patterns of antibiotic resistance in enteric bacteria. Several mechanisms are responsible for the ability of microorganisms to tolerate antibiotics, and the incidence of resistance to these compounds within bacterial species has increased since the commercial use of antibiotics became widespread. To establish the extent of and changes in the diversity of antibiotic resistance patterns in natural populations, we determined the MICs of five antibiotics for collections of enteric bacteria isolated from diverse hosts and geographic locations and during periods before and after commercial application of antibiotics began. All of the pre-antibiotic era strains were susceptible to high levels of these antibiotics, whereas 20% of strains from contemporary populations of Escherichia coli and Salmonella enterica displayed high-level resistance to at least one of the antibiotics. In addition to the increase in the frequency of high-level resistance, background levels, conferred by genes providing nonspecific low-level resistance to multiple antibiotics, were significantly higher among contemporary strains. Changes in the incidence and levels of antibiotic resistance are not confined to particular segments of the bacterial population and reflect responses to the increased exposure of bacteria to antimicrobial compounds over the past several decades. | 2000 | 11097921 |
| 3872 | 3 | 0.9999 | Functional metagenomic analysis reveals rivers are a reservoir for diverse antibiotic resistance genes. The environment harbours a significant diversity of uncultured bacteria and a potential source of novel and extant resistance genes which may recombine with clinically important bacteria disseminated into environmental reservoirs. There is evidence that pollution can select for resistance due to the aggregation of adaptive genes on mobile elements. The aim of this study was to establish the impact of waste water treatment plant (WWTP) effluent disposal to a river by using culture independent methods to study diversity of resistance genes downstream of the WWTP in comparison to upstream. Metagenomic libraries were constructed in Escherichia coli and screened for phenotypic resistance to amikacin, gentamicin, neomycin, ampicillin and ciprofloxacin. Resistance genes were identified by using transposon mutagenesis. A significant increase downstream of the WWTP was observed in the number of phenotypic resistant clones recovered in metagenomic libraries. Common β-lactamases such as blaTEM were recovered as well as a diverse range of acetyltransferases and unusual transporter genes, with evidence for newly emerging resistance mechanisms. The similarities of the predicted proteins to known sequences suggested origins of genes from a very diverse range of bacteria. The study suggests that waste water disposal increases the reservoir of resistance mechanisms in the environment either by addition of resistance genes or by input of agents selective for resistant phenotypes. | 2014 | 24636906 |
| 3830 | 4 | 0.9999 | Resistance 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. | 2019 | 30530714 |
| 4650 | 5 | 0.9999 | Co-occurrence of resistance to different antibiotics among aquatic bacteria. BACKGROUND: Antibiotic resistance is not confined to pathogens, but is also widespread in various natural environments. In nature the microbes producing antibiotic compounds have been around for millions of years. Heavy use of antibiotics in medicine and veterinary practice may lead to the accumulation of resistance genes in microbial populations, followed by a rise in multiresistant bacteria. RESULTS: To test the extent of resistance among aquatic bacteria, we have collected 760 isolates resistant to at least one antibiotic. The phylogeny of the isolates covers a wide range of Proteobacteria, Actinobacteria and Bacteroidetes. In order to determine the extent of multiresistance, the isolates were tested on six antibiotics. As the growth rate of the different bacteria was highly variable, the classical medical resistance tests could not be used, and an alternative method considering the full growth curve was developed. In general, the overall resistances to different antibiotics could be explained by random, independent distribution. An exception to this was the resistances against tetracycline and chloramphenicol, which tended to occur in pairs. CONCLUSIONS: We conclude that there is no massive spread of multiresistance determinants in the studied environment, although some specific cases can be found, awaiting for molecular characterization of the resistance mechanisms. | 2012 | 23031674 |
| 4653 | 6 | 0.9998 | Modelling the effectiveness of surveillance based on metagenomics in detecting, monitoring, and forecasting antimicrobial resistance in livestock production under economic constraints. Current surveillance of antimicrobial resistance (AMR) is mostly based on testing indicator bacteria using minimum inhibitory concentration (MIC) panels. Metagenomics has the potential to identify all known antimicrobial resistant genes (ARGs) in complex samples and thereby detect changes in the occurrence earlier. Here, we simulate the results of an AMR surveillance program based on metagenomics in the Danish pig population. We modelled both an increase in the occurrence of ARGs and an introduction of a new ARG in a few farms and the subsequent spread to the entire population. To make the simulation realistic, the total cost of the surveillance was constrained, and the sampling schedule was set at one pool per month with 5, 20, 50, or 100 samples. Our simulations demonstrate that a pool of 20-50 samples and a sequencing depth of 250 million fragments resulted in the shortest time to detection in both scenarios, with a time delay to detection of change of [Formula: see text]15 months in all scenarios. Compared with culture-based surveillance, our simulation indicates that there are neither significant reductions nor increases in time to detect a change using metagenomics. The benefit of metagenomics is that it is possible to monitor all known resistance in one sampling and laboratory procedure in contrast to the current monitoring that is based on the phenotypic characterisation of selected indicator bacterial species. Therefore, overall changes in AMR in a population will be detected earlier using metagenomics due to the fact that the resistance gene does not have to be transferred to and expressed by an indicator bacteria before it is possible to detect. | 2023 | 37990114 |
| 3884 | 7 | 0.9998 | Distribution 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. | 2012 | 23133629 |
| 4654 | 8 | 0.9998 | Early Bacterial Colonization and Antibiotic Resistance Gene Acquisition in Newborns. Several studies have recently identified the main factors contributing to the bacterial colonization of newborns and the dynamics of the infant microbiome development. However, most of these studies address large time periods of weeks or months after birth, thereby missing on important aspects of the early microbiome maturation, such as the acquisition of antibiotic resistance determinants during postpartum hospitalization. The pioneer bacterial colonization and the extent of its associated antibiotic resistance gene (ARG) dissemination during this early phase of life are largely unknown. Studies addressing resistant bacteria or ARGs in neonates often focus only on the presence of particular bacteria or genes from a specific group of antibiotics. In the present study, we investigated the gut-, the oral-, and the skin-microbiota of neonates within the first 72 h after birth using 16S rDNA sequencing approaches. In addition, we screened the neonates and their mothers for the presence of 20 different ARGs by directed TaqMan qPCR assays. The taxonomic analysis of the newborn samples revealed an important shift of the microbiota during the first 72 h after birth, showing a clear site-specific colonization pattern in this very early time frame. Moreover, we report a substantial acquisition of ARGs during postpartum hospitalization, with a very high incidence of macrolide resistance determinants and mecA detection across different body sites of the newborns. This study highlights the importance of antibiotic resistance determinant dissemination in neonates during hospitalization, and the need to investigate the implication of the mothers and the hospital environment as potential sources of ARGs. | 2020 | 32754449 |
| 4148 | 9 | 0.9998 | Plasmids in the environment. Bacterial plasmids existed in bacteria before the antibiotic era but their presence was brought into prominence by the use of antibiotics which selected for antibiotic resistant strains. Subsequently, the range of genes carried on plasmids was shown to extend far beyond those coding for antibiotic resistance. Any consideration of plasmids in the environment, therefore, must include all plasmids whether or not they are genetically linked with antibiotic resistance. Antibiotic resistant bacteria may be found in the environment either by contamination with excreta from man and animals in which the strains were selected, or by their selection within the environment by antibiotics synthesized in situ or reaching the environment in an undegraded form in sewage from man and animals, or from industry. Other agents, also contaminating the environment, exert a selective pressure such as heavy metals in industrial effluents which select for metal resistance. This paper reviews the incidences and role of plasmids in various habitats including natural waters, soil, pastures, farm wastes, and human sewage from both hospitalised and other populations. Aspects of plasmid ecology, their biological role, and the transmissibility of genetic material between bacteria within the environment are considered. Two recent studies in Bristol, UK, are reported. The first was a genetic study on Escherichia coli isolates from calf slurry. Various DNA probes were used to determine the extent of gene exchange between the various serotypes within the natural environment. The second was a preliminary study to determine the stability of a recombinant plasmid, in a wild strain of Escherichia coli of pig origin, after its release into a semi-contained farm situation. It is now recognized that plasmids are widely distributed in bacterial populations in terrestrial and aquatic environments. Many have been detected by their carriage of genes coding for antibiotic or heavy metal resistance. Others, mainly cryptic in nature, have been demonstrated by plasmid profile studies on isolates from various habitats. Plasmids were shown to be present in a relatively few bacteria deposited in culture collections prior to the antibiotic era. Subsequently, the increased prevalence of R plasmids in bacteria in most ecosystems were due mainly to the selective pressure imposed by the use of antibiotics. This pressure may have been exerted either in the environment in which the strains were found or elsewhere, the environment subsequently being contaminated by antibiotic resistant bacteria.(ABSTRACT TRUNCATED AT 400 WORDS) | 1988 | 3074480 |
| 9656 | 10 | 0.9998 | Use of sequence barcodes for tracking horizontal gene transfer of antimicrobial resistance genes in a microbial community. One of the most important knowledge gaps in the antimicrobial resistance crisis is the lack of understanding regarding how genes spread from their environmental origins to bacteria pathogenic to humans. In this study our aim was to create a system that allows the conduction of experiments in laboratory settings that mimic the complexity of natural communities with multiple resistance genes and mobile genetic elements circulating at the same time. Here we report a new sequence-based barcode system that allows simultaneous tracking of the spread of antimicrobial resistance genes from multiple genetic origins. We tested this concept with an experiment in which we added an antimicrobial resistance gene to different genetic environments in alive and dead donors and let the gene spread naturally in an artificial microbial community under different environmental conditions to provide examples of factors that can be investigated. We used emulsion, paired-isolation, and concatenation polymerase chain reaction to detect the new gene carriers and metagenomic analysis to see changes in the genetic environment. We observed the genes moving and were able to recognise the barcode from the gene sequences, thus validating the idea of barcode use. We also saw that temperature and gene origin had effects on the number of new host species. Our results confirmed that our system worked and can be further developed for more complicated experiments. | 2025 | 40800620 |
| 3343 | 11 | 0.9998 | Shotgun 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. | 2014 | 25520706 |
| 9653 | 12 | 0.9998 | Evaluating 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. | 2016 | 27767072 |
| 4649 | 13 | 0.9998 | Factors affecting the measurement of antibiotic resistance in bacteria isolated from lake water. It is more difficult to obtain a reliable assessment of antibiotic resistance in populations of aquatic bacteria than in those populations which are well characterized (e.g. bacteria of medical and veterinary significance). Factors which influence the results include the bacterial taxa involved, their site of origin and the methods and media used to isolate and subculture the bacteria, and to perform the sensitivity tests. Examples of these effects are provided. The resistance profiles obtained with populations of aquatic pseudomonads depend on the species composition of the population. Resistance patterns in aquatic bacteria varied with the site from which they were isolated; a higher incidence of resistance was recorded along shorelines and in sheltered bays than in the open water. The inclusion of antibiotics in the media employed for primary isolation increased the number of individual and multiple resistances recorded. A similar effect was observed with increased inoculum size in the sensitivity disc method but this could be reversed by raising the incubation temperature. The medium used to conduct the test also affected the results and many aquatic bacteria failed to grow on media such as Iso-Sensitest Agar. It is recommended that the sensitivity disc method is adopted for aquatic bacteria because it permits interpretation of a wider range of response. Comparison of the incidence of antibiotic resistance in different habitats will remain meaningless, however, until comprehensive methods for the identification of bacteria are developed and the techniques used for sensitivity testing are standardized. | 1986 | 3636321 |
| 3818 | 14 | 0.9998 | A study of the transfer of tetracycline resistance genes between Escherichia coli in the intestinal tract of a mouse and a chicken model. Experiments to demonstrate the transfer of genes within a natural environment are technically difficult because of the unknown numbers and strains of bacteria present, as well as difficulties designing adequate control experiments. The results of such studies should be viewed within the limits of the experimental design. Most experiments to date have been based on artificial models, which only give approximations of the real-life situation. The current study uses more natural models and provides information about tetracycline resistance as it occurs in wild-type bacteria within the environment of the normal intestinal tract of an animal. Tetracycline sensitive, nalidixic acid resistant Escherichia coli isolates of human origin were administered to mice and chicken animal models. They were monitored for acquisition of tetracycline resistance from indigenous or administered donor E. coli. Five sets of in vivo experiments demonstrated unequivocal transfer of tetracycline resistance to tetracycline sensitive recipients. The addition of tetracycline in the drinking water of the animals increased the probability of transfer between E. coli strains originating from the same animal species. The co-transfer of unselected antibiotic resistance in animal models was also demonstrated. | 2006 | 16930278 |
| 4127 | 15 | 0.9998 | The 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. | 2021 | 34065307 |
| 4109 | 16 | 0.9998 | Antibiotic use in plant agriculture. Antibiotics have been used since the 1950s to control certain bacterial diseases of high-value fruit, vegetable, and ornamental plants. Today, the antibiotics most commonly used on plants are oxytetracycline and streptomycin. In the USA, antibiotics applied to plants account for less than 0.5% of total antibiotic use. Resistance of plant pathogens to oxytetracycline is rare, but the emergence of streptomycin-resistant strains of Erwinia amylovora, Pseudomonas spp., and Xanthomonas campestris has impeded the control of several important diseases. A fraction of streptomycin-resistance genes in plant-associated bacteria are similar to those found in bacteria isolated from humans, animals, and soil, and are associated with transfer-proficient elements. However, the most common vehicles of streptomycin-resistance genes in human and plant pathogens are genetically distinct. Nonetheless, the role of antibiotic use on plants in the antibiotic-resistance crisis in human medicine is the subject of debate. | 2002 | 12147767 |
| 3871 | 17 | 0.9998 | Functional characterization of bacteria isolated from ancient arctic soil exposes diverse resistance mechanisms to modern antibiotics. Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes. | 2015 | 25807523 |
| 4146 | 18 | 0.9998 | Aquatic Environments as Hotspots of Transferable Low-Level Quinolone Resistance and Their Potential Contribution to High-Level Quinolone Resistance. The disposal of antibiotics in the aquatic environment favors the selection of bacteria exhibiting antibiotic resistance mechanisms. Quinolones are bactericidal antimicrobials extensively used in both human and animal medicine. Some of the quinolone-resistance mechanisms are encoded by different bacterial genes, whereas others are the result of mutations in the enzymes on which those antibiotics act. The worldwide occurrence of quinolone resistance genes in aquatic environments has been widely reported, particularly in areas impacted by urban discharges. The most commonly reported quinolone resistance gene, qnr, encodes for the Qnr proteins that protect DNA gyrase and topoisomerase IV from quinolone activity. It is important to note that low-level resistance usually constitutes the first step in the development of high-level resistance, because bacteria carrying these genes have an adaptive advantage compared to the highly susceptible bacterial population in environments with low concentrations of this antimicrobial group. In addition, these genes can act additively with chromosomal mutations in the sequences of the target proteins of quinolones leading to high-level quinolone resistance. The occurrence of qnr genes in aquatic environments is most probably caused by the release of bacteria carrying these genes through anthropogenic pollution and maintained by the selective activity of antimicrobial residues discharged into these environments. This increase in the levels of quinolone resistance has consequences both in clinical settings and the wider aquatic environment, where there is an increased exposure risk to the general population, representing a significant threat to the efficacy of quinolone-based human and animal therapies. In this review the potential role of aquatic environments as reservoirs of the qnr genes, their activity in reducing the susceptibility to various quinolones, and the possible ways these genes contribute to the acquisition and spread of high-level resistance to quinolones will be discussed. | 2022 | 36358142 |
| 3828 | 19 | 0.9998 | Interaction with a phage gene underlie costs of a β-lactamase. The fitness cost of an antibiotic resistance gene (ARG) can differ across host strains, creating refuges that allow the maintenance of an ARG in the absence of direct selection for its resistance phenotype. Despite the importance of such ARG-host interactions for predicting ARG dynamics, the basis of ARG fitness costs and their variability between hosts are not well understood. We determined the genetic basis of a host-dependent cost of a β-lactamase, bla(TEM-116*), that conferred a significant cost in one Escherichia coli strain but was close to neutral in 11 other Escherichia spp. strains. Selection of a bla(TEM-116*)-encoding plasmid in the strain in which it initially had a high cost resulted in rapid and parallel compensation for that cost through mutations in a P1-like phage gene, relA(P1). When the wild-type relA(P1) gene was added to a strain in which it was not present and in which bla(TEM-116*) was neutral, it caused the ARG to become costly. Thus, relA(P1) is both necessary and sufficient to explain bla(TEM-116*) costs in at least some host backgrounds. To our knowledge, these findings represent the first demonstrated case of the cost of an ARG being influenced by a genetic interaction with a phage gene. The interaction between a phage gene and a plasmid-borne ARG highlights the complexity of selective forces determining the maintenance and spread of ARGs and, by extension, encoding phage and plasmids in natural bacterial communities.IMPORTANCEAntibiotic resistance genes (ARGs) play a major role in the increasing problem of antibiotic resistance in clinically relevant bacteria. Selection of these genes occurs in the presence of antibiotics, but their eventual success also depends on the sometimes substantial costs they impose on host bacteria in antibiotic-free environments. We evolved an ARG that confers resistance to penicillin-type antibiotics in one host in which it did confer a cost and in one host in which it did not. We found that costs were rapidly and consistently reduced through parallel genetic changes in a gene encoded by a phage that was infecting the costly host. The unmutated version of this gene was sufficient to cause the ARG to confer a cost in a host in which it was originally neutral, demonstrating an antagonism between the two genetic elements and underlining the range and complexity of pressures determining ARG dynamics in natural populations. | 2024 | 38194254 |