Horizontal gene transfer as a biosafety issue: a natural phenomenon of public concern. - Related Documents




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971001.0000Horizontal gene transfer as a biosafety issue: a natural phenomenon of public concern. The transfer of genetic information between distantly or even unrelated organisms during evolution had been inferred from nucleotide sequence comparisons. These studies provided circumstantial evidence that in rare cases genes had been laterally transmitted amongst organisms of the domains bacteria, archaea and eukarya. Laboratory-based studies confirmed that the gene pools of the various domains of organisms are linked. Amongst the bacterial gene exchange mechanisms transduction, transformation and conjugation, the latter was identified as the mechanism with potentially the broadest host range of transfer. Previously, the issue of horizontal gene transfer has become important in the context of biosafety. Gene transfer studies carried out under more natural conditions such as in model ecosystems or in the environment established that all gene transfer mechanisms worked under these conditions. Moreover, environmental hot-spots were identified where favourable conditions such as nutrient enrichment increased the probability of genetic exchange among bacteria. In particular, the phytosphere was shown to provide conducive conditions for conjugative gene exchange. Concern has been expressed that transfer of recombinant DNA (e.g. antibiotic resistance genes) from genetically modified organisms (GMOs) such as transgenic plants to phytosphere bacteria may occur and thus contribute to the undesirable spread of antibiotic resistance determinants. Studies which were performed to address this issue clearly showed that such a transfer occurs, if at all, at extremely low frequency.19989823660
928610.9999Bacterial sex in dental plaque. Genes are transferred between bacteria in dental plaque by transduction, conjugation, and transformation. Membrane vesicles can also provide a mechanism for horizontal gene transfer. DNA transfer is considered bacterial sex, but the transfer is not parallel to processes that we associate with sex in higher organisms. Several examples of bacterial gene transfer in the oral cavity are given in this review. How frequently this occurs in dental plaque is not clear, but evidence suggests that it affects a number of the major genera present. It has been estimated that new sequences in genomes established through horizontal gene transfer can constitute up to 30% of bacterial genomes. Gene transfer can be both inter- and intrageneric, and it can also affect transient organisms. The transferred DNA can be integrated or recombined in the recipient's chromosome or remain as an extrachromosomal inheritable element. This can make dental plaque a reservoir for antimicrobial resistance genes. The ability to transfer DNA is important for bacteria, making them better adapted to the harsh environment of the human mouth, and promoting their survival, virulence, and pathogenicity.201323741559
417020.9999The 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.202540098486
930930.9998Plasmid 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.200818193080
417540.9998Resistance gene transfer in anaerobes: new insights, new problems. Investigations of antibiotic-resistance gene transfer elements in Bacteroides species have generated some new insights into how bacteria transfer resistance genes and what environmental conditions foster gene transfer. Integrated gene transfer elements, called conjugative transposons, appear to be responsible for much of the transfer of resistance genes among Bacteroides species. Conjugative transposons not only transfer themselves but also mobilize coresident plasmids and excise and mobilize unlinked integrated elements. Less is known about resistance gene transfer elements of the gram-positive anaerobes, but there are some indications that similar elements may be found in them as well. An unusual feature of the Bacteroides conjugative transposons is that transfer of many of them is stimulated considerably by low concentrations of antibiotics. Thus, antibiotics not only select for resistant strains but also can stimulate transfer of the resistance gene in the first place. This finding raises questions about whether use of low-dose tetracycline therapy may have a greater effect on the resident microflora than had been previously thought. Finally, investigations of resistance genes in Bacteroides species and other genera of bacteria have begun to provide evidence that the resident microflora of the human body does indeed act as a reservoir for resistance genes, which may be acquired from and passed on the transient colonizers of the site.19968953105
416850.9998Various 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.201223482877
969660.9998Evolution 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.19938212510
969870.9998Potential impact of environmental bacteriophages in spreading antibiotic resistance genes. The idea that bacteriophage transduction plays a role in the horizontal transfer of antibiotic resistance genes is gaining momentum. Such transduction might be vital in horizontal transfer from environmental to human body-associated biomes and here we review many lines of evidence supporting this notion. It is well accepted that bacteriophages are the most abundant entities in most environments, where they have been shown to be quite persistent. This fact, together with the ability of many phages to infect bacteria belonging to different taxa, makes them suitable vehicles for gene transfer. Metagenomic studies confirm that substantial percentages of the bacteriophage particles present in most environments contain bacterial genes, including mobile genetic elements and antibiotic resistance genes. When specific genes of resistance to antibiotics are detected by real-time PCR in the bacteriophage populations of different environments, only tenfold lower numbers of these genes are observed, compared with those found in the corresponding bacterial populations. In addition, the antibiotic resistance genes from these bacteriophages are functional and generate resistance to the bacteria when these genes are transfected. Finally, reports about the transduction of antibiotic resistance genes are on the increase.201323701331
928580.9998Bacterial genetic exchange in nature. Most bacteria are haploid organisms containing only one copy of each gene per cell for most of the growth cycle. This means that the chance for correcting random mutations in bacterial genes would depend entirely on the complementarity inherent in DNA structures, unless homologous DNA sequences can be imported from outside the cell. Bacteria, like all living organisms have evolved at least one autonomous mechanism, conjugation, for exchanging portions of genetic materials between two related cells. The ecological benefits of conjugation include the expansion of metabolic versatility and resistance to hazardous environmental conditions. Natural bacterial genetic exchange also occurs through virus infections (transduction) and through the uptake of extracellular DNA (transformation). The origin and ecological benefits of transduction and transformation are difficult to assess because they are driven by factors external to the affected cell. Bacterial genetic exchange has implications for the evolution of phenotypes that are either beneficial to humans, such as biodegradation of toxic xenobiotic chemicals, or that are detrimental, such as the evolution of pathogenesis and the spread of antibiotic resistance. Understanding natural bacterial genetic exchange mechanisms is also relevant to the assessment of dispersal risks associated with genetically engineered bacteria and recombinant genes in the environment.19958533067
417190.9998Plasmids 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.202236142804
9284100.9998The population and evolutionary dynamics of homologous gene recombination in bacterial populations. In bacteria, recombination is a rare event, not a part of the reproductive process. Nevertheless, recombination -- broadly defined to include the acquisition of genes from external sources, i.e., horizontal gene transfer (HGT) -- plays a central role as a source of variation for adaptive evolution in many species of bacteria. Much of niche expansion, resistance to antibiotics and other environmental stresses, virulence, and other characteristics that make bacteria interesting and problematic, is achieved through the expression of genes and genetic elements obtained from other populations of bacteria of the same and different species, as well as from eukaryotes and archaea. While recombination of homologous genes among members of the same species has played a central role in the development of the genetics and molecular biology of bacteria, the contribution of homologous gene recombination (HGR) to bacterial evolution is not at all clear. Also, not so clear are the selective pressures responsible for the evolution and maintenance of transformation, the only bacteria-encoded form of HGR. Using a semi-stochastic simulation of mutation, recombination, and selection within bacterial populations and competition between populations, we explore (1) the contribution of HGR to the rate of adaptive evolution in these populations and (2) the conditions under which HGR will provide a bacterial population a selective advantage over non-recombining or more slowly recombining populations. The results of our simulation indicate that, under broad conditions: (1) HGR occurring at rates in the range anticipated for bacteria like Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, and Bacillus subtilis will accelerate the rate at which a population adapts to environmental conditions; (2) once established in a population, selection for this capacity to increase rates of adaptive evolution can maintain bacteria-encoded mechanisms of recombination and prevent invasion of non-recombining populations, even when recombination engenders a modest fitness cost; and (3) because of the density- and frequency-dependent nature of HGR in bacteria, this capacity to increase rates of adaptive evolution is not sufficient as a selective force to provide a recombining population a selective advantage when it is rare. Under realistic conditions, homologous gene recombination will increase the rate of adaptive evolution in bacterial populations and, once established, selection for higher rates of evolution will promote the maintenance of bacteria-encoded mechanisms for HGR. On the other hand, increasing rates of adaptive evolution by HGR is unlikely to be the sole or even a dominant selective pressure responsible for the original evolution of transformation.200919680442
9706110.9998Antibiotic resistance markers in genetically modified plants: a risk to human health? Cotransformation with an antibiotic-resistance marker is often necessary in the process of creating a genetically modified (GM) plant. Concern has been expressed that the release of these markers in GM plants may result in an increase in the rate of antibiotic resistance in human pathogens. For such an event to occur, DNA must not be totally degraded in field conditions, and the antibiotic-resistance marker must encounter potential recipient bacteria and be taken up by them, before being integrated into the bacterial genome, and the genes then expressed. In addition, the new recombinant must overcome the physiological disadvantage of acquisition of a piece of foreign DNA, probably in conditions where the new gene does not provide a selective advantage. We review each of these stages, summarising the investigations that have followed each of these steps. We contrast the potential increase in the antibiotic resistance reservoir created by antibiotic-resistance markers in GM plants with the current situation created by medical antibiotic prescribing. We conclude that, although fragments of DNA large enough to contain an antibiotic-resistance gene may survive in the environment, the barriers to transfer, incorporation, and transmission are so substantial that any contribution to antibiotic resistance made by GM plants must be overwhelmed by the contribution made by antibiotic prescription in clinical practice.200516183518
9711120.9998Horizontal DNA transfer between bacteria in the environment. In the environment horizontal DNA transfer between various bacterial species and genera takes place by transformation, transduction, but mainly by conjugation. Conjugation is responsible for the spread of genes coding for antibiotic resistance and xenobiotic degradation. Transfer events are reported in animal, rhizosphere and phylloplane ecosystems and in non polluted and polluted water and soil. Genetic exchange between Bacteria and Archaea is also observed. Evaluation of the extent of interspecies gene transfer is crucial in view of the deliberate release of a variety of unmodified and genetically modified microorganisms into the natural environments.200314743976
9296130.9998Genome plasticity: insertion sequence elements, transposons and integrons, and DNA rearrangement. Living organisms are defined by the genes they possess. Control of expression of this gene set, both temporally and in response to the environment, determines whether an organism can survive changing conditions and can compete for the resources it needs to reproduce. Bacteria are no exception; changes to the genome will, in general, threaten the ability of the microbe to survive, but acquisition of new genes may enhance its chances of survival by allowing growth in a previously hostile environment. For example, acquisition of an antibiotic resistance gene by a bacterial pathogen can permit it to thrive in the presence of an antibiotic that would otherwise kill it; this may compromise clinical treatments. Many forces, chemical and genetic, can alter the genetic content of DNA by locally changing its nucleotide sequence. Notable for genetic change in bacteria are transposable elements and site-specific recombination systems such as integrons. Many of the former can mobilize genes from one replicon to another, including chromosome-plasmid translocation, thus establishing conditions for interspecies gene transfer. Balancing this, transposition activity can result in loss or rearrangement of DNA sequences. This chapter discusses bacterial DNA transfer systems, transposable elements and integrons, and the contributions each makes towards the evolution of bacterial genomes, particularly in relation to bacterial pathogenesis. It highlights the variety of phylogenetically distinct transposable elements, the variety of transposition mechanisms, and some of the implications of rearranging DNA, and addresses the effects of genetic change on the fitness of the microbe.200415148416
9699140.9998Bottlenecks in the transferability of antibiotic resistance from natural ecosystems to human bacterial pathogens. It is generally accepted that resistance genes acquired by human pathogens through horizontal gene transfer originated in environmental, non-pathogenic bacteria. As a consequence, there is increasing concern on the roles that natural, non-clinical ecosystems, may play in the evolution of resistance. Recent studies have shown that the variability of determinants that can provide antibiotic resistance on their expression in a heterologous host is much larger than what is actually found in human pathogens, which implies the existence of bottlenecks modulating the transfer, spread, and stability of antibiotic resistance genes. In this review, the role that different factors such as founder effects, ecological connectivity, fitness costs, or second-order selection may have on the establishment of a specific resistance determinant in a population of bacterial pathogens is analyzed.201122319513
9493150.9998Regulatory integration of horizontally-transferred genes in bacteria. Horizontal transfer of genetic material is a fact of microbial life and bacteria can obtain new DNA sequences through the processes of conjugation, transduction and transformation. This offers the bacterium the possibility of evolving rapidly by importing new genes that code for new traits that may assist in environmental adaptation. Research in this area has focused in particular on the role of horizontal transfer in the dissemination through bacterial populations of genes for resistance to antimicrobial agents, including antibiotics. It is becoming clear that many other phenotypic characteristics have been acquired through horizontal routes and that these include traits contributing to pathogenesis and symbiosis. An important corollary to the acquisition of new genes is the problem of how best to integrate them in the existing gene regulatory circuits of the recipient so that fitness is not compromised initially and can be enhanced in the future through optimal expression of the new genes.200919273337
3837160.9998Evolutionary 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.201626668183
9695170.9998Antibiotic resistance with particular reference to soil microorganisms. Evidence of increasing resistance to antibiotics in soil and other natural isolates highlights the importance of horizontal transfer of resistance genes in facilitating gene flux in bacteria. Horizontal gene transfer in bacteria is favored by the presence of mobile genetic elements and by the organization of bacterial genomes into operons allowing for the cooperative transfer of genes with related functions. The selective pressure for the spread of resistance genes correlates strongly with the clinical and agricultural overuse of antibiotics. The future of antimicrobial chemotherapy may lie in developing new antimicrobials using information from comparative functional microbial genomics to find genetic targets for antimicrobials and also to understand gene expression enabling selective targeting of genes with expression that correlates with the infectious process.200111446510
9295180.9998Biological activities specified by antibiotic resistance plasmids. Bacteria can display resistance to a wide spectrum of noxious agents and environmental conditions, and these properties are often mediated by genes located on extrachromosomal DNA elements called plasmids. Replication, vertical and horizontal transmission and evolution of these elements are discussed, and examples of the genes responsible for the resistance phenotypes are given. Selective forces that drive the evolution of new combinations of bacterial properties of particular importance in clinical situations are analysed.19863542928
9838190.9998Interactions between plasmids and other mobile genetic elements affect their transmission and persistence. Plasmids are genetic elements that play a role in bacterial evolution by providing new genes that promote adaptation to diverse conditions. Plasmids are also known to reduce bacterial competitiveness in the absence of selection for plasmid-encoded traits. It is easier to understand plasmid persistence when considering the evidence that plasmid maintenance can improve during co-evolution with the bacterial host, i.e. the chromosome. However, bacteria isolated from nature often harbor diverse mobile elements: phages, transposons, genomic islands and even other plasmids. Recent interest has emerged on the role such elements play on the persistence and evolution of plasmids. Here, we mainly review interactions between different plasmids, but also discuss their interactions with other genetic elements. We focus on interactions that impact fundamental plasmid traits, such as the fitness effect imposed on their hosts and the transfer efficiency into new host cells. We illustrate these phenomena with examples concerning clinically relevant organisms and the spread of plasmids carrying antibiotic resistance genes and virulence factors.201930771401