Mobilizable genomic islands, different strategies for the dissemination of multidrug resistance and other adaptive traits. - Related Documents




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983701.0000Mobilizable genomic islands, different strategies for the dissemination of multidrug resistance and other adaptive traits. Mobile genetic elements are near ubiquitous DNA segments that revealed a surprising variety of strategies for their propagation among prokaryotes and between eukaryotes. In bacteria, conjugative elements were shown to be key drivers of evolution and adaptation by efficiently disseminating genes involved in pathogenicity, symbiosis, metabolic pathways, and antibiotic resistance. Conjugative plasmids of the incompatibility groups A and C (A/C) are important vehicles for the dissemination of antibiotic resistance and the consequent global emergence and spread of multi-resistant pathogenic bacteria. Beyond their own mobility, A/C plasmids were also shown to drive the mobility of unrelated non-autonomous mobilizable genomic islands, which may also confer further advantageous traits. In this commentary, we summarize the current knowledge on different classes of A/C-dependent mobilizable genomic islands and we discuss other DNA hitchhikers and their implication in bacterial evolution. Furthermore, we glimpse at the complex genetic network linking autonomous and non-autonomous mobile genetic elements, and at the associated flow of genetic information between bacteria.201728439449
416510.9999A modular master on the move: the Tn916 family of mobile genetic elements. The Tn916 family is a group of mobile genetic elements that are widespread among many commensal and pathogenic bacteria. These elements are found primarily, but not exclusively, in the Firmicutes. They are integrated into the bacterial genome and are capable of conjugative transfer to a new host and, often, intracellular transposition to a different genomic site - hence their name: 'conjugative transposons', or 'integrative conjugative elements'. An increasing variety of Tn916 relatives are being reported from different bacteria, harbouring genes coding for resistance to various antibiotics and the potential to encode other functions, such as lantibiotic immunity. This family of mobile genetic elements has an extraordinary ability to acquire accessory genes, making them important vectors in the dissemination of various traits among environmental, commensal and clinical bacteria. These elements are also responsible for genome rearrangements, providing considerable raw material on which natural selection can act. Therefore, the study of this family of mobile genetic elements is essential for a better understanding and control of the current rise of antibiotic resistance among pathogenic bacteria.200919464182
983820.9999Interactions 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
983630.9999Staphylococcus aureus mobile genetic elements. Among the bacteria groups, most of them are known to be beneficial to human being whereas only a minority is being recognized as harmful. The pathogenicity of bacteria is due, in part, to their rapid adaptation in the presence of selective pressures exerted by the human host. In addition, through their genomes, bacteria are subject to mutations, various rearrangements or horizontal gene transfer among and/or within bacterial species. Bacteria's essential metabolic functions are generally encoding by the core genes. Apart of the core genes, there are several number of mobile genetic elements (MGE) acquired by horizontal gene transfer that might be beneficial under certain environmental conditions. These MGE namely bacteriophages, transposons, plasmids, and pathogenicity islands represent about 15% Staphylococcus aureus genomes. The acquisition of most of the MGE is made by horizontal genomic islands (GEI), recognized as discrete DNA segments between closely related strains, transfer. The GEI contributes to the wide spread of microorganisms with an important effect on their genome plasticity and evolution. The GEI are also involve in the antibiotics resistance and virulence genes dissemination. In this review, we summarize the mobile genetic elements of S. aureus.201424728610
416440.9999Broad-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.201323471189
416350.9999The integron/gene cassette system: an active player in bacterial adaptation. The integron includes a site-specific recombination system capable of integrating and expressing genes contained in structures called mobile gene cassettes. Integrons were originally identified on mobile elements from pathogenic bacteria and were found to be a major reservoir of antibiotic-resistance genes. Integrons are now known to be ancient structures that are phylogenetically diverse and, to date, have been found in approximately 9% of sequenced bacterial genomes. Overall, gene diversity in cassettes is extraordinarily high, suggesting that the integron/gene cassette system has a broad role in adaptation rather than being confined to simply conferring resistance to antibiotics. In this chapter, we provide a review of the integron/gene cassette system highlighting characteristics associated with this system, diversity of elements contained within it, and their importance in driving bacterial evolution and consequently adaptation. Ideas on the evolution of gene cassettes and gene cassette arrays are discussed.200919271181
417060.9999The 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
400970.9999Unraveling the role of mobile genetic elements in antibiotic resistance transmission and defense strategies in bacteria. Irrational antibiotic use contributes to the development of antibiotic resistance in bacteria, which is a major cause of healthcare-associated infections globally. Molecular research has shown that multiple resistance frequently develops from the uptake of pre-existing resistance genes, which are subsequently intensified under selective pressures. Resistant genes spread and are acquired through mobile genetic elements which are essential for facilitating horizontal gene transfer. MGEs have been identified as carriers of genetic material and are a significant player in evolutionary processes. These include insertion sequences, transposons, integrative and conjugative elements, plasmids, and genomic islands, all of which can transfer between and within DNA molecules. With an emphasis on pathogenic bacteria, this review highlights the salient features of the MGEs that contribute to the development and spread of antibiotic resistance. MGEs carry non-essential genes, including AMR and virulence genes, which can enhance the adaptability and fitness of their bacterial hosts. These elements employ evolutionary strategies to facilitate their replication and dissemination, thus enabling survival without positive selection for the harboring of beneficial genes.202540810119
930880.9999Integrons: 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.200111587934
984890.9999Cargo Genes of Tn7-Like Transposons Comprise an Enormous Diversity of Defense Systems, Mobile Genetic Elements, and Antibiotic Resistance Genes. Transposition is a major mechanism of horizontal gene mobility in prokaryotes. However, exploration of the genes mobilized by transposons (cargo) is hampered by the difficulty in delineating integrated transposons from their surrounding genetic context. Here, we present a computational approach that allowed us to identify the boundaries of 6,549 Tn7-like transposons. We found that 96% of these transposons carry at least one cargo gene. Delineation of distinct communities in a gene-sharing network demonstrates how transposons function as a conduit of genes between phylogenetically distant hosts. Comparative analysis of the cargo genes reveals significant enrichment of mobile genetic elements (MGEs) nested within Tn7-like transposons, such as insertion sequences and toxin-antitoxin modules, and of genes involved in recombination, anti-MGE defense, and antibiotic resistance. More unexpectedly, cargo also includes genes encoding central carbon metabolism enzymes. Twenty-two Tn7-like transposons carry both an anti-MGE defense system and antibiotic resistance genes, illustrating how bacteria can overcome these combined pressures upon acquisition of a single transposon. This work substantially expands the distribution of Tn7-like transposons, defines their evolutionary relationships, and provides a large-scale functional classification of prokaryotic genes mobilized by transposition. IMPORTANCE Transposons are major vehicles of horizontal gene transfer that, in addition to genes directly involved in transposition, carry cargo genes. However, characterization of these genes is hampered by the difficulty of identification of transposon boundaries. We developed a computational approach for detecting transposon ends and applied it to perform a comprehensive census of the cargo genes of Tn7-like transposons, a large class of bacterial mobile genetic elements (MGE), many of which employ a unique, CRISPR-mediated mechanism of site-specific transposition. The cargo genes encompass a striking diversity of MGE, defense, and antibiotic resistance systems. Unexpectedly, we also identified cargo genes encoding metabolic enzymes. Thus, Tn7-like transposons mobilize a vast repertoire of genes that can have multiple effects on the host bacteria.202134872347
9309100.9998Plasmid 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
3837110.9998Evolutionary 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
4133120.9998Importance 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.200111432416
9849130.9998Analysis of antibiotic resistance regions in Gram-negative bacteria. Antibiotic resistance in Gram-negative bacteria is often due to the acquisition of resistance genes from a shared pool. In multiresistant isolates these genes, together with associated mobile elements, may be found in complex conglomerations on plasmids or on the chromosome. Analysis of available sequences reveals that these multiresistance regions (MRR) are modular, mosaic structures composed of different combinations of components from a limited set arranged in a limited number of ways. Components common to different MRR provide targets for homologous recombination, allowing these regions to evolve by combinatorial evolution, but our understanding of this process is far from complete. Advances in technology are leading to increasing amounts of sequence data, but currently available automated annotation methods usually focus on identifying ORFs and predicting protein function by homology. In MRR, where the genes are often well characterized, the challenge is to identify precisely which genes are present and to define the boundaries of complete and fragmented mobile elements. This review aims to summarize the types of mobile elements involved in multiresistance in Gram-negative bacteria and their associations with particular resistance genes, to describe common components of MRR and to illustrate methods for detailed analysis of these regions.201121564142
4162140.9998Gene sharing among plasmids and chromosomes reveals barriers for antibiotic resistance gene transfer. The emergence of antibiotic resistant bacteria is a major threat to modern medicine. Rapid adaptation to antibiotics is often mediated by the acquisition of plasmids carrying antibiotic resistance (ABR) genes. Nonetheless, the determinants of plasmid-mediated ABR gene transfer remain debated. Here, we show that the propensity of ABR gene transfer via plasmids is higher for accessory chromosomal ABR genes in comparison with core chromosomal ABR genes, regardless of the resistance mechanism. Analysing the pattern of ABR gene occurrence in the genomes of 2635 Enterobacteriaceae isolates, we find that 33% of the 416 ABR genes are shared between chromosomes and plasmids. Phylogenetic reconstruction of ABR genes occurring on both plasmids and chromosomes supports their evolution by lateral gene transfer. Furthermore, accessory ABR genes (encoded in less than 10% of the chromosomes) occur more abundantly in plasmids in comparison with core ABR genes (encoded in greater than or equal to 90% of the chromosomes). The pattern of ABR gene occurrence in plasmids and chromosomes is similar to that in the total Escherichia genome. Our results thus indicate that the previously recognized barriers for gene acquisition by lateral gene transfer apply also to ABR genes. We propose that the functional complexity of the underlying ABR mechanism is an important determinant of ABR gene transferability. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.202234839702
9850150.9998Annotation and Comparative Genomics of Prokaryotic Transposable Elements. The data generated in nearly 30 years of bacterial genome sequencing has revealed the abundance of transposable elements (TE) and their importance in genome and transcript remodeling through the mediation of DNA insertions and deletions, structural rearrangements, and regulation of gene expression. Furthermore, what we have learned from studying transposition mechanisms and their regulation in bacterial TE is fundamental to our current understanding of TE in other organisms because much of what has been observed in bacteria is conserved in all domains of life. However, unlike eukaryotic TE, prokaryotic TE sequester and transmit important classes of genes that impact host fitness, such as resistance to antibiotics and heavy metals and virulence factors affecting animals and plants, among other acquired traits. This provides dynamism and plasticity to bacteria, which would otherwise be propagated clonally. The insertion sequences (IS), the simplest form of prokaryotic TE, are autonomous and compact mobile genetic elements. These can be organized into compound transposons, in which two similar IS can flank any DNA segment and render it transposable. Other more complex structures, called unit transposons, can be grouped into four major families (Tn3, Tn7, Tn402, Tn554) with specific genetic characteristics. This chapter will revisit the prominent structural features of these elements, focusing on a genomic annotation framework and comparative analysis. Relevant aspects of TE will also be presented, stressing their key position in genome impact and evolution, especially in the emergence of antimicrobial resistance and other adaptive traits.202438819561
3785160.9998A network approach to decipher the dynamics of Lysobacteraceae plasmid gene sharing. Plasmids provide an efficient vehicle for gene sharing among bacterial populations, playing a key role in bacterial evolution. Network approaches are particularly suitable to represent multipartite relationships and are useful tools to characterize plasmid-mediated gene sharing events. The bacterial family Lysobacteraceae includes plant commensal, plant pathogenic and opportunistic human pathogens for which plasmid-mediated adaptation has been reported. We searched for homologues of plasmid gene sequences from this family in the entire diversity of available bacterial genome sequences and built a network of plasmid gene sharing from the results. While plasmid genes are openly shared between the bacteria of the family Lysobacteraceae, taxonomy strongly defined the boundaries of these exchanges, which only barely reached other families. Most inferred plasmid gene sharing events involved a few genes only, and evidence of full plasmid transfers were restricted to taxonomically closely related taxa. We detected multiple plasmid-chromosome gene transfers, including the known sharing of a heavy metal resistance transposon. In the network, bacterial lifestyles shaped substructures of isolates colonizing specific ecological niches and harbouring specific types of resistance genes. Genes associated with pathogenicity or antibiotic and metal resistance were among those that most importantly structured the network, highlighting the imprints of human-mediated selective pressure on pathogenic populations. A massive sequencing effort on environmental Lysobacteraceae is therefore required to refine our understanding of how this reservoir fuels the emergence and the spread of genes among this family and its potential impact on plant, animal and human health.202335593155
9295170.9998Biological 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
4371180.9998Independent origins and evolution of the secondary replicons of the class Gammaproteobacteria. Multipartite genomes, consisting of more than one replicon, have been found in approximately 10 % of bacteria, many of which belong to the phylum Proteobacteria. Many aspects of their origin and evolution, and the possible advantages related to this type of genome structure, remain to be elucidated. Here, we performed a systematic analysis of the presence and distribution of multipartite genomes in the class Gammaproteobacteria, which includes several genera with diverse lifestyles. Within this class, multipartite genomes are mainly found in the order Alteromonadales (mostly in the genus Pseudoalteromonas) and in the family Vibrionaceae. Our data suggest that the emergence of secondary replicons in Gammaproteobacteria is rare and that they derive from plasmids. Despite their multiple origins, we highlighted the presence of evolutionary trends such as the inverse proportionality of the genome to chromosome size ratio, which appears to be a general feature of bacteria with multipartite genomes irrespective of taxonomic group. We also highlighted some functional trends. The core gene set of the secondary replicons is extremely small, probably limited to essential genes or genes that favour their maintenance in the genome, while the other genes are less conserved. This hypothesis agrees with the idea that the primary advantage of secondary replicons could be to facilitate gene acquisition through horizontal gene transfer, resulting in replicons enriched in genes associated with adaptation to different ecological niches. Indeed, secondary replicons are enriched both in genes that could promote adaptation to harsh environments, such as those involved in antibiotic, biocide and metal resistance, and in functional categories related to the exploitation of environmental resources (e.g. carbohydrates), which can complement chromosomal functions.202337185344
9651190.9998Host- plasmid network structure in wastewater is linked to antimicrobial resistance genes. As mobile genetic elements, plasmids are central for our understanding of antimicrobial resistance spread in microbial communities. Plasmids can have varying fitness effects on their host bacteria, which will markedly impact their role as antimicrobial resistance vectors. Using a plasmid population model, we first show that beneficial plasmids interact with a higher number of hosts than costly plasmids when embedded in a community with multiple hosts and plasmids. We then analyse the network of a natural host-plasmid wastewater community from a Hi-C metagenomics dataset. As predicted by the model, we find that antimicrobial resistance encoding plasmids, which are likely to have positive fitness effects on their hosts in wastewater, interact with more bacterial taxa than non-antimicrobial resistance plasmids and are disproportionally important for connecting the entire network compared to non- antimicrobial resistance plasmids. This highlights the role of antimicrobials in restructuring host-plasmid networks by increasing the benefits of antimicrobial resistance carrying plasmids, which can have consequences for the spread of antimicrobial resistance genes through microbial networks. Furthermore, that antimicrobial resistance encoding plasmids are associated with a broader range of hosts implies that they will be more robust to turnover of bacterial strains.202438228585