# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 3837 | 0 | 1.0000 | Evolutionary Paths That Expand Plasmid Host-Range: Implications for Spread of Antibiotic Resistance. The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-host-range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into the mechanisms by which the host range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid host-range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin-antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple naïve hosts, acquisition of this transposon also expanded the plasmid's host range, which has important implications for the spread of antibiotic resistance. | 2016 | 26668183 |
| 3836 | 1 | 0.9999 | Bacterial recombination promotes the evolution of multi-drug-resistance in functionally diverse populations. Bacterial recombination is believed to be a major factor explaining the prevalence of multi-drug-resistance (MDR) among pathogenic bacteria. Despite extensive evidence for exchange of resistance genes from retrospective sequence analyses, experimental evidence for the evolutionary benefits of bacterial recombination is scarce. We compared the evolution of MDR between populations of Acinetobacter baylyi in which we manipulated both the recombination rate and the initial diversity of strains with resistance to single drugs. In populations lacking recombination, the initial presence of multiple strains resistant to different antibiotics inhibits the evolution of MDR. However, in populations with recombination, the inhibitory effect of standing diversity is alleviated and MDR evolves rapidly. Moreover, only the presence of DNA harbouring resistance genes promotes the evolution of resistance, ruling out other proposed benefits for recombination. Together, these results provide direct evidence for the fitness benefits of bacterial recombination and show that this occurs by mitigation of functional interference between genotypes resistant to single antibiotics. Although analogous to previously described mechanisms of clonal interference among alternative beneficial mutations, our results actually highlight a different mechanism by which interactions among co-occurring strains determine the benefits of recombination for bacterial evolution. | 2012 | 22048956 |
| 9310 | 2 | 0.9999 | Bacterial resistance to antibiotics. Effective antibacterial drugs have been available for nearly 50 years. After the introduction of each new such drug, whether chemically synthesized or a naturally occurring antibiotic, bacterial resistance to it has emerged. The genetic mechanisms by which bacteria have acquired resistance were quite unexpected; a new evolutionary pathways has been revealed. Although some antibiotic resistance has resulted from mutational changes in structural proteins--targets for the drugs' action--most has resulted from the acquisition of new, ready-made genes from an external source--that is, from another bacterium. Vectors of the resistance genes are plasmids--heritable DNA molecules that are transmissible between bacterial cells. Plasmids without antibiotic-resistance genes are common in all kinds of bacteria. Resistance plasmids have resulted from the insertion of new DNA sequences into previously existing plasmids. Thus, the spread of antibiotic resistance is at three levels: bacteria between people or animals; plasmids between bacteria; and transposable genes between plasmids. | 1984 | 6319093 |
| 9308 | 3 | 0.9999 | Integrons: natural tools for bacterial genome evolution. Integrons were first identified as the primary mechanism for antibiotic resistance gene capture and dissemination among Gram-negative bacteria. More recently, their role in genome evolution has been extended with the discovery of larger integron structures, the super-integrons, as genuine components of the genomes of many species throughout the gamma-proteobacterial radiation. The functional platforms of these integrons appear to be sedentary, whereas their gene cassette contents are highly variable. Nevertheless, the gene cassettes for which an activity has been experimentally demonstrated encode proteins related to simple adaptive functions and their recruitment is seen as providing the bacterial host with a selective advantage. The widespread occurrence of the integron system among Gram-negative bacteria is discussed, with special focus on the super-integrons. Some of the adaptive functions encoded by these genes are also reviewed, and implications of integron-mediated genome evolution in the emergence of novel bacterial species are highlighted. | 2001 | 11587934 |
| 9309 | 4 | 0.9999 | Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria. Bacteria have existed on Earth for three billion years or so and have become adept at protecting themselves against toxic chemicals. Antibiotics have been in clinical use for a little more than 6 decades. That antibiotic resistance is now a major clinical problem all over the world attests to the success and speed of bacterial adaptation. Mechanisms of antibiotic resistance in bacteria are varied and include target protection, target substitution, antibiotic detoxification and block of intracellular antibiotic accumulation. Acquisition of genes needed to elaborate the various mechanisms is greatly aided by a variety of promiscuous gene transfer systems, such as bacterial conjugative plasmids, transposable elements and integron systems, that move genes from one DNA system to another and from one bacterial cell to another, not necessarily one related to the gene donor. Bacterial plasmids serve as the scaffold on which are assembled arrays of antibiotic resistance genes, by transposition (transposable elements and ISCR mediated transposition) and site-specific recombination mechanisms (integron gene cassettes).The evidence suggests that antibiotic resistance genes in human bacterial pathogens originate from a multitude of bacterial sources, indicating that the genomes of all bacteria can be considered as a single global gene pool into which most, if not all, bacteria can dip for genes necessary for survival. In terms of antibiotic resistance, plasmids serve a central role, as the vehicles for resistance gene capture and their subsequent dissemination. These various aspects of bacterial resistance to antibiotics will be explored in this presentation. | 2008 | 18193080 |
| 4168 | 5 | 0.9999 | Various pathways leading to the acquisition of antibiotic resistance by natural transformation. Natural transformation can lead to exchange of DNA between taxonomically diverse bacteria. In the case of chromosomal DNA, homology-based recombination with the recipient genome is usually necessary for heritable stability. In our recent study, we have shown that natural transformation can promote the transfer of transposons, IS elements, and integrons and gene cassettes, largely independent of the genetic relationship between the donor and recipient bacteria. Additional results from our study suggest that natural transformation with species-foreign DNA might result in the uptake of a wide range of DNA fragments; leading to changes in the antimicrobial susceptibility profile and contributing to the generation of antimicrobial resistance in bacteria. | 2012 | 23482877 |
| 9312 | 6 | 0.9999 | Why There Are No Essential Genes on Plasmids. Mobile genetic elements such as plasmids are important for the evolution of prokaryotes. It has been suggested that there are differences between functions coded for by mobile genes and those in the "core" genome and that these differences can be seen between plasmids and chromosomes. In particular, it has been suggested that essential genes, such as those involved in the formation of structural proteins or in basic metabolic functions, are rarely located on plasmids. We model competition between genotypically varying bacteria within a single population to investigate whether selection favors a chromosomal location for essential genes. We find that in general, chromosomal locations for essential genes are indeed favored. This is because the inheritance of chromosomes is more stable than that for plasmids. We define the "degradation" rate as the rate at which chance genetic processes, for example, mutation, deletion, or translocation, render essential genes nonfunctioning. The only way in which plasmids can be a location for functioning essential genes is if chromosomal genes degrade faster than plasmid genes. If the two degradation rates are equal, or if plasmid genes degrade faster than chromosomal genes, functioning essential genes will be found only on chromosomes. | 2015 | 25540453 |
| 4133 | 7 | 0.9999 | Importance of integrons in the diffusion of resistance. Horizontal transfer of resistance genes is a successful mechanism for the transmission and dissemination of multiple drug resistance among bacterial pathogens. The impact of horizontally transmitted genetic determinants in the evolution of resistance is particularly evident when resistance genes are physically associated in clusters and transferred en bloc to the recipient cell. Recent advances in the molecular characterisation of antibiotic resistance mechanisms have highlighted the existence of genetic structures. called integrons, involved in the acquisition of resistance genes. These DNA elements have frequently been reported in multi-drug resistant strains isolated from animals and humans, and are located either on the bacterial chromosome or on broad-host-range plasmids. The role of integrons in the development of multiple resistance relies on their unique capacity to cluster and express drug resistance genes. Moreover, the spread of resistance genes among different replicons and their exchange between plasmid and bacterial chromosome are facilitated by the integration of integrons into transposable elements. The association of a highly efficient gene capture and expression system, together with the capacity for vertical and horizontal transmission of resistance genes represents a powerful weapon used by bacteria to combat the assault of antibiotics. | 2001 | 11432416 |
| 9267 | 8 | 0.9999 | Off-Target Integron Activity Leads to Rapid Plasmid Compensatory Evolution in Response to Antibiotic Selection Pressure. Integrons are mobile genetic elements that have played an important role in the dissemination of antibiotic resistance. Under stress, the integron can generate combinatorial variation in resistance cassette expression by cassette reshuffling, accelerating the evolution of resistance. However, the flexibility of the integron integrase site recognition motif hints at potential off-target effects of the integrase on the rest of the genome that may have important evolutionary consequences. Here, we test this hypothesis by selecting for increased-piperacillin-resistance populations of Pseudomonas aeruginosa with a mobile integron containing a difficult-to-mobilize β-lactamase cassette to minimize the potential for adaptive cassette reshuffling. We found that integron activity can decrease the overall survival rate but also improve the fitness of the surviving populations. Off-target inversions mediated by the integron accelerated plasmid adaptation by disrupting costly conjugative genes otherwise mutated in control populations lacking a functional integrase. Plasmids containing integron-mediated inversions were associated with lower plasmid costs and higher stability than plasmids carrying mutations albeit at the cost of a reduced conjugative ability. These findings highlight the potential for integrons to create structural variation that can drive bacterial evolution, and they provide an interesting example showing how antibiotic pressure can drive the loss of conjugative genes. IMPORTANCE Tackling the public health challenge created by antibiotic resistance requires understanding the mechanisms driving its evolution. Mobile integrons are widespread genetic platforms heavily involved in the spread of antibiotic resistance. Through the action of the integrase enzyme, integrons allow bacteria to capture, excise, and shuffle antibiotic resistance gene cassettes. This integrase enzyme is characterized by its ability to recognize a wide range of recombination sites, which allows it to easily capture diverse resistance cassettes but which may also lead to off-target reactions with the rest of the genome. Using experimental evolution, we tested the off-target impact of integron activity. We found that integrons increased the fitness of the surviving bacteria through extensive genomic rearrangements of the plasmids carrying the integrons, reducing their ability to spread horizontally. These results show that integrons not only accelerate resistance evolution but also can generate extensive structural variation, driving bacterial evolution beyond antibiotic resistance. | 2023 | 36840554 |
| 9311 | 9 | 0.9999 | Various plasmid strategies limit the effect of bacterial restriction-modification systems against conjugation. In bacteria, genes conferring antibiotic resistance are mostly carried on conjugative plasmids, mobile genetic elements that spread horizontally between bacterial hosts. Bacteria carry defence systems that defend them against genetic parasites, but how effective these are against plasmid conjugation is poorly understood. Here, we study to what extent restriction-modification (RM) systems-by far the most prevalent bacterial defence systems-act as a barrier against plasmids. Using 10 different RM systems and 13 natural plasmids conferring antibiotic resistance in Escherichia coli, we uncovered variation in defence efficiency ranging from none to 105-fold protection. Further analysis revealed genetic features of plasmids that explain the observed variation in defence levels. First, the number of RM recognition sites present on the plasmids generally correlates with defence levels, with higher numbers of sites being associated with stronger defence. Second, some plasmids encode methylases that protect against restriction activity. Finally, we show that a high number of plasmids in our collection encode anti-restriction genes that provide protection against several types of RM systems. Overall, our results show that it is common for plasmids to encode anti-RM strategies, and that, as a consequence, RM systems form only a weak barrier for plasmid transfer by conjugation. | 2024 | 39413206 |
| 3835 | 10 | 0.9999 | Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria. The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of bla(TEM-1) expression in Escherichia coli MG1655, we showed that plasmid copy number variability stably maintains populations composed of cells with both low and high plasmid copy numbers. This diversity in plasmid copy number enhances the probability of bacterial survival in the presence of antibiotics, while also rapidly reducing the burden of carrying multiple plasmids in drug-free environments. Our results further support the tenet that multicopy plasmids not only act as vehicles for the horizontal transfer of genetic information between cells but also as drivers of bacterial adaptation, enabling rapid modulation of gene copy numbers. Understanding the role of multicopy plasmids in antibiotic resistance is critical, and our study provides insights into how bacteria can transiently survive lethal concentrations of antibiotics. | 2024 | 38521779 |
| 3827 | 11 | 0.9999 | The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli. Antimicrobial resistance (AMR) in bacteria implies a tradeoff between the benefit of resistance under antimicrobial selection pressure and the incurred fitness cost in the absence of antimicrobials. The fitness cost of a resistance determinant is expected to depend on its genetic support, such as a chromosomal mutation or a plasmid acquisition, and on its impact on cell metabolism, such as an alteration in an essential metabolic pathway or the production of a new enzyme. To provide a global picture of the factors that influence AMR fitness cost, we conducted a systematic review and meta-analysis focused on a single species, Escherichia coli. By combining results from 46 high-quality studies in a multilevel meta-analysis framework, we find that the fitness cost of AMR is smaller when provided by horizontally transferable genes such as those encoding beta-lactamases, compared to mutations in core genes such as those involved in fluoroquinolone and rifampicin resistance. We observe that the accumulation of acquired AMR genes imposes a much smaller burden on the host cell than the accumulation of AMR mutations, and we provide quantitative estimates of the additional cost of a new gene or mutation. These findings highlight that gene acquisition is more efficient than the accumulation of mutations to evolve multidrug resistance, which can contribute to the observed dominance of horizontally transferred genes in the current AMR epidemic. | 2023 | 37455716 |
| 4170 | 12 | 0.9999 | The Spread of Antibiotic Resistance Is Driven by Plasmids Among the Fastest Evolving and of Broadest Host Range. Microorganisms endure novel challenges for which other microorganisms in other biomes may have already evolved solutions. This is the case of nosocomial bacteria under antibiotic therapy because antibiotics are of ancient natural origin and resistances to them have previously emerged in environmental bacteria. In such cases, the rate of adaptation crucially depends on the acquisition of genes by horizontal transfer of plasmids from distantly related bacteria in different biomes. We hypothesized that such processes should be driven by plasmids among the most mobile and evolvable. We confirmed these predictions by showing that plasmid species encoding antibiotic resistance are very mobile, have broad host ranges, while showing higher rates of homologous recombination and faster turnover of gene repertoires than the other plasmids. These characteristics remain outstanding when we remove resistance plasmids from our dataset, suggesting that antibiotic resistance genes are preferentially acquired and carried by plasmid species that are intrinsically very mobile and plastic. Evolvability and mobility facilitate the transfer of antibiotic resistance, and presumably of other phenotypes, across distant taxonomic groups and biomes. Hence, plasmid species, and possibly those of other mobile genetic elements, have differentiated and predictable roles in the spread of novel traits. | 2025 | 40098486 |
| 9896 | 13 | 0.9999 | Interbacterial Transfer of Carbapenem Resistance and Large Antibiotic Resistance Islands by Natural Transformation in Pathogenic Acinetobacter. Acinetobacter baumannii infection poses a major health threat, with recurrent treatment failure due to antibiotic resistance, notably to carbapenems. While genomic analyses of clinical strains indicate that homologous recombination plays a major role in the acquisition of antibiotic resistance genes, the underlying mechanisms of horizontal gene transfer often remain speculative. Our understanding of the acquisition of antibiotic resistance is hampered by the lack of experimental systems able to reproduce genomic observations. We here report the detection of recombination events occurring spontaneously in mixed bacterial populations and which can result in the acquisition of resistance to carbapenems. We show that natural transformation is the main driver of intrastrain but also interstrain recombination events between A. baumannii clinical isolates and pathogenic species of Acinetobacter. We observed that interbacterial natural transformation in mixed populations is more efficient at promoting the acquisition of large resistance islands (AbaR4 and AbaR1) than when the same bacteria are supplied with large amounts of purified genomic DNA. Importantly, analysis of the genomes of the recombinant progeny revealed large recombination tracts (from 13 to 123 kb) similar to those observed in the genomes of clinical isolates. Moreover, we highlight that transforming DNA availability is a key determinant of the rate of recombinants and results from both spontaneous release and interbacterial predatory behavior. In the light of our results, natural transformation should be considered a leading mechanism of genome recombination and horizontal gene transfer of antibiotic resistance genes in Acinetobacter baumannii. IMPORTANCE Acinetobacter baumannii is a multidrug-resistant pathogen responsible for difficult-to-treat hospital-acquired infections. Understanding the mechanisms leading to the emergence of the multidrug resistance in this pathogen today is crucial. Horizontal gene transfer is assumed to largely contribute to this multidrug resistance. However, in A. baumannii, the mechanisms leading to genome recombination and the horizontal transfer of resistance genes are poorly understood. We describe experimental evidence that natural transformation, a horizontal gene transfer mechanism recently highlighted in A. baumannii, allows the highly efficient interbacterial transfer of genetic elements carrying resistance to last-line antibiotic carbapenems. Importantly, we demonstrated that natural transformation, occurring in mixed populations of Acinetobacter, enables the transfer of large resistance island-mobilizing multiple-resistance genes. | 2022 | 35073754 |
| 9696 | 14 | 0.9999 | Evolution of resistance in microorganisms of human origin. Resistance to antimicrobials in bacteria results from either evolution of "new" DNA or from variation in existing DNA. Evidence suggests that new DNA did not originate since the use of antibiotics in medicine, but evolved long ago in soil bacteria. This evidence is based on functional and structural homologies of resistance proteins in human pathogens, and resistance proteins or physiological proteins of soil bacteria. Variation in existing DNA has been shown to comprise variations in structural or regulatory genes of the normal chromosome or mutations in already existing plasmid-mediated resistance genes modifying the resistance phenotype. The success of R-determinants in human pathogens was due to their horizontal spread by transformation, transduction and conjugation. Furthermore, transposition has enabled bacteria to efficiently distribute R-determinants between independent DNA-molecules. Since the genetic processes involved in the development of resistance are rare events, the selective pressure exerted by antibiotics has significantly contributed to the overall evolutionary picture. With few exceptions, experimental data about the role of antibiotic usage outside human medicine with respect to the resistance problem in human pathogens are missing. Epidemiological data about the occurrence of resistance in human pathogens seem to indicate that the major contributing factor to the problem we face today was the extensive use of antibiotics in medicine itself. | 1993 | 8212510 |
| 4164 | 15 | 0.9999 | Broad-host-range IncP-1 plasmids and their resistance potential. The plasmids of the incompatibility (Inc) group IncP-1, also called IncP, as extrachromosomal genetic elements can transfer and replicate virtually in all Gram-negative bacteria. They are composed of backbone genes that encode a variety of essential functions and accessory genes that have implications for human health and environmental bioremediation. Broad-host-range IncP plasmids are known to spread genes between distinct phylogenetic groups of bacteria. These genes often code for resistances to a broad spectrum of antibiotics, heavy metals, and quaternary ammonium compounds used as disinfectants. The backbone of these plasmids carries modules that enable them to effectively replicate, move to a new host via conjugative transfer and to be stably maintained in bacterial cells. The adaptive, resistance, and virulence genes are mainly located on mobile genetic elements integrated between the functional plasmid backbone modules. Environmental studies have demonstrated the wide distribution of IncP-like replicons in manure, soils and wastewater treatment plants. They also are present in strains of pathogenic or opportunistic bacteria, which can be a cause for concern, because they may encode multiresistance. Their broad distribution suggests that IncP plasmids play a crucial role in bacterial adaptation by utilizing horizontal gene transfer. This review summarizes the variety of genetic information and physiological functions carried by IncP plasmids, which can contribute to the spread of antibiotic and heavy metal resistance while also mediating the process of bioremediation of pollutants. Due to the location of the resistance genes on plasmids with a broad-host-range and the presence of transposons carrying these genes it seems that the spread of these genes would be possible and quite hazardous in infection control. Future studies are required to determine the level of risk of the spread of resistance genes located on these plasmids. | 2013 | 23471189 |
| 4171 | 16 | 0.9999 | Plasmids as Key Players in Acinetobacter Adaptation. This review briefly summarizes the data on the mechanisms of development of the adaptability of Acinetobacters to various living conditions in the environment and in the clinic. A comparative analysis of the genomes of free-living and clinical strains of A. lwoffii, as well as the genomes of A. lwoffii and A. baumannii, has been carried out. It has been shown that plasmids, both large and small, play a key role in the formation of the adaptability of Acinetobacter to their living conditions. In particular, it has been demonstrated that the plasmids of various strains of Acinetobacter differ from each other in their structure and gene composition depending on the lifestyle of their host bacteria. Plasmids of modern strains are enriched with antibiotic-resistant genes, while the content of genes involved in resistance to heavy metals and arsenic is comparable to plasmids from modern and ancient strains. It is concluded that Acinetobacter plasmids may ensure the survival of host bacteria under conditions of various types of environmental and clinical stresses. A brief overview of the main mechanisms of horizontal gene transfer on plasmids inherent in Acinetobacter strains is also given. | 2022 | 36142804 |
| 3796 | 17 | 0.9999 | The presence of plasmids in bacterial hosts alters phage isolation and infectivity. Antibiotic resistance genes are often carried by plasmids, which spread intra- and inter genera bacterial populations, and also play a critical role in bacteria conferring phage resistance. However, it remains unknown about the influence of plasmids present in bacterial hosts on phage isolation and subsequent infectivity. In this study, using both Escherichia coli and Pseudomonas putida bacteria containing different plasmids, eight phages were isolated and characterized in terms of phage morphology and host range analysis, in conjunction with DNA and protein sequencing. We found that plasmids can influence both the phage isolation process and phage infectivity. In particular, the isolated phages exhibited different phage plaquing infectivity towards the same bacterial species containing different plasmids. Furthermore, the presence of plasmids was found to alter the expression of bacteria membrane protein, which correlates with bacterial cell surface receptors recognized by phages, thus affecting phage isolation and infectivity. Given the diverse and ubiquitous nature of plasmids, our findings highlight the need to consider plasmids as factors that can influence both phage isolation and infectivity. | 2022 | 37938681 |
| 3828 | 18 | 0.9999 | 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 |
| 3833 | 19 | 0.9999 | Fight evolution with evolution: plasmid-dependent phages with a wide host range prevent the spread of antibiotic resistance. The emergence of pathogenic bacteria resistant to multiple antibiotics is a serious worldwide public health concern. Whenever antibiotics are applied, the genes encoding for antibiotic resistance are selected for within bacterial populations. This has led to the prevalence of conjugative plasmids that carry resistance genes and can transfer themselves between diverse bacterial groups. In this study, we investigated whether it is feasible to attempt to prevent the spread of antibiotic resistances with a lytic bacteriophage, which can replicate in a wide range of gram-negative bacteria harbouring conjugative drug resistance-conferring plasmids. The counter-selection against the plasmid was shown to be effective, reducing the frequency of multidrug-resistant bacteria that formed via horizontal transfer by several orders of magnitude. This was true also in the presence of an antibiotic against which the plasmid provided resistance. Majority of the multiresistant bacteria subjected to phage selection also lost their conjugation capability. Overall this study suggests that, while we are obligated to maintain the selection for the spread of the drug resistances, the 'fight evolution with evolution' approach could help us even out the outcome to our favour. | 2013 | 24062801 |