# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9852 | 0 | 1.0000 | Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance. Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes. | 2018 | 29551265 |
| 9306 | 1 | 0.9998 | Establishment Genes Present on pLS20 Family of Conjugative Plasmids Are Regulated in Two Different Ways. During conjugation, a conjugative DNA element is transferred from a donor to a recipient cell via a connecting channel. Conjugation has clinical relevance because it is the major route for spreading antibiotic resistance and virulence genes. The conjugation process can be divided into different steps. The initial steps carried out in the donor cell culminate in the transfer of a single DNA strand (ssDNA) of the conjugative element into the recipient cell. However, stable settlement of the conjugative element in the new host requires at least two additional events: conversion of the transferred ssDNA into double-stranded DNA and inhibition of the hosts' defence mechanisms to prevent degradation of the transferred DNA. The genes involved in this late step are historically referred to as establishment genes. The defence mechanisms of the host must be inactivated rapidly and-importantly-transiently, because prolonged inactivation would make the cell vulnerable to the attack of other foreign DNA, such as those of phages. Therefore, expression of the establishment genes in the recipient cell has to be rapid but transient. Here, we studied regulation of the establishment genes present on the four clades of the pLS20 family of conjugative plasmids harboured by different Bacillus species. Evidence is presented that two fundamentally different mechanisms regulate the establishment genes present on these plasmids. Identification of the regulatory sequences were critical in revealing the establishment regulons. Remarkably, whereas the conjugation genes involved in the early steps of the conjugation process are conserved and are located in a single large operon, the establishment genes are highly variable and organised in multiple operons. We propose that the mosaical distribution of establishment genes in multiple operons is directly related to the variability of defence genes encoded by the host bacterial chromosomes. | 2021 | 34946067 |
| 9822 | 2 | 0.9998 | Molecular mechanisms for transposition of drug-resistance genes and other movable genetic elements. Transposition is proposed to be responsible for the rapid evolution of multiply drug-resistant bacterial strains. Transposons, which carry the genes encoding drug resistance, are linear pieces of DNA that range in size from 2.5 to 23 kilobase pairs and always contain at their ends nucleotide sequences repeated in inverse order. In some transposons the terminal inverted repeat sequences are capable of independent movement and are called insertion sequences. Transposons carry a gene that encodes transposase(s), the enzyme(s) responsible for recombination of the transposon into another DNA molecule. Studies on transposable genetic elements in bacteria have not only given insight into the spread of antibiotic resistance but also into the process of DNA movement. | 1987 | 3035697 |
| 9307 | 3 | 0.9998 | Integrons. Integrons are genetic elements able to acquire and rearrange open reading frames (ORFs) embedded in gene cassette units and convert them to functional genes by ensuring their correct expression. They were originally identified as a mechanism used by Gram-negative bacteria to collect antibiotic resistance genes and express multiple resistance phenotypes in synergy with transposons. More recently, their role has been broadened with the discovery of chromosomal integron (CI) structures in the genomes of hundreds of bacterial species. This review focuses on the resources carried in these elements, on their unique recombination mechanisms, and on the different mechanisms controlling the cassette dynamics. We discuss the role of the toxin/antitoxin (TA) cassettes for the stabilization of the large cassette arrays carried in the larger CIs, known as superintegrons. Finally, we explore the central role played by single-stranded DNA in the integron cassette dynamics in light of the recent discovery that the integron integrase expression is controlled by the SOS response. | 2010 | 20707672 |
| 9303 | 4 | 0.9998 | A Conserved Class II Type Thioester Domain-Containing Adhesin Is Required for Efficient Conjugation in Bacillus subtilis. Conjugation, the process by which a DNA element is transferred from a donor to a recipient cell, is the main horizontal gene transfer route responsible for the spread of antibiotic resistance and virulence genes. Contact between a donor and a recipient cell is a prerequisite for conjugation, because conjugative DNA is transferred into the recipient via a channel connecting the two cells. Conjugative elements encode proteins dedicated to facilitating the recognition and attachment to recipient cells, also known as mating pair formation. A subgroup of the conjugative elements is able to mediate efficient conjugation during planktonic growth, and mechanisms facilitating mating pair formation will be particularly important in these cases. Conjugative elements of Gram-negative bacteria encode conjugative pili, also known as sex pili, some of which are retractile. Far less is known about mechanisms that promote mating pair formation in Gram-positive bacteria. The conjugative plasmid pLS20 of the Gram-positive bacterium Bacillus subtilis allows efficient conjugation in liquid medium. Here, we report the identification of an adhesin gene in the pLS20 conjugation operon. The N-terminal region of the adhesin contains a class II type thioester domain (TED) that is essential for efficient conjugation, particularly in liquid medium. We show that TED-containing adhesins are widely conserved in Gram-positive bacteria, including pathogens where they often play crucial roles in pathogenesis. Our study is the first to demonstrate the involvement of a class II type TED-containing adhesin in conjugation.IMPORTANCE Bacterial resistance to antibiotics has become a serious health care problem. The spread of antibiotic resistance genes between bacteria of the same or different species is often mediated by a process named conjugation, where a donor cell transfers DNA to a recipient cell through a connecting channel. The first step in conjugation is recognition and attachment of the donor to a recipient cell. Little is known about this first step, particularly in Gram-positive bacteria. Here, we show that the conjugative plasmid pLS20 of Bacillus subtilis encodes an adhesin protein that is essential for effective conjugation. This adhesin protein has a structural organization similar to adhesins produced by other Gram-positive bacteria, including major pathogens, where the adhesins serve in attachment to host tissues during colonization and infection. Our findings may thus also open novel avenues to design drugs that inhibit the spread of antibiotic resistance by blocking the first recipient-attachment step in conjugation. | 2021 | 33727345 |
| 9296 | 5 | 0.9997 | Genome 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. | 2004 | 15148416 |
| 9829 | 6 | 0.9997 | Promiscuous transfer of drug resistance in gram-negative bacteria. Bacterial conjugation is a major mechanism for the spread of antibiotic-resistance genes in pathogenic organisms. In gram-negative bacteria, broad-host-range drug-resistance plasmids mediate genetic exchange between many unrelated species. The mechanism of conjugation encoded by the broad-host-range IncP plasmid RK2 has been studied in detail. The location and sequence of the transfer origin of RK2 has been determined. Several barriers limit plasmid transfer between unrelated bacteria: interactions at the cell surface may prevent effective mating contact, restriction systems may degrade foreign DNA, or the plasmid may not replicate in the new host. RK2 has evolved specific mechanisms by which it overcomes these barriers; this plasmid can mediate the transfer of resistance to most gram-negative bacteria. | 1984 | 6143782 |
| 9830 | 7 | 0.9997 | Mechanisms of Conjugative Transfer and Type IV Secretion-Mediated Effector Transport in Gram-Positive Bacteria. Conjugative DNA transfer is the most important means to transfer antibiotic resistance genes and virulence determinants encoded by plasmids, integrative conjugative elements (ICE), and pathogenicity islands among bacteria. In gram-positive bacteria, there exist two types of conjugative systems, (i) type IV secretion system (T4SS)-dependent ones, like those encoded by the Enterococcus, Streptococcus, Staphylococcus, Bacillus, and Clostridia mobile genetic elements and (ii) T4SS-independent ones, as those found on Streptomyces plasmids. Interestingly, very recently, on the Streptococcus suis genome, the first gram-positive T4SS not only involved in conjugative DNA transfer but also in effector translocation to the host was detected. Although no T4SS core complex structure from gram-positive bacteria is available, several structures from T4SS protein key factors from Enterococcus and Clostridia plasmids have been solved. In this chapter, we summarize the current knowledge on the molecular mechanisms and structure-function relationships of the diverse conjugation machineries and emerging research needs focused on combatting infections and spread of multiple resistant gram-positive pathogens. | 2017 | 29536357 |
| 9312 | 8 | 0.9997 | 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 |
| 9283 | 9 | 0.9997 | Vibrio cholerae: Measuring Natural Transformation Frequency. Many bacteria can become naturally competent to take up extracellular DNA across their outer and inner membranes by a dedicated competence apparatus. Whereas some studies show that the DNA delivered to the cytoplasm may be used for genome repair or for nutrition, it can also be recombined onto the chromosome by homologous recombination: a process called natural transformation. Along with conjugation and transduction, natural transformation represents a mechanism for horizontal transfer of genetic material, e.g., antibiotic resistance genes, which can confer new beneficial characteristics onto the recipient bacteria. Described here are protocols for quantifying the frequency of transformation for the human pathogen Vibrio cholerae, one of several Vibrio species recently shown to be capable of natural transformation. | 2014 | 25367272 |
| 9311 | 10 | 0.9997 | 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 |
| 4168 | 11 | 0.9997 | 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 |
| 9305 | 12 | 0.9997 | Control of genes for conjugative transfer of plasmids and other mobile elements. Conjugative transfer is a primary means of spread of mobile genetic elements (plasmids and transposons) between bacteria.It leads to the dissemination and evolution of the genes (such as those conferring resistance to antibiotics) which are carried by the plasmid. Expression of the plasmid genes needed for conjugative transfer is tightly regulated so as to minimise the burden on the host. For plasmids such as those belonging to the IncP group this results in downregulation of the transfer genes once all bacteria have a functional conjugative apparatus. For F-like plasmids (apart from F itself which is a derepressed mutant) tight control results in very few bacteria having a conjugative apparatus. Chance encounters between the rare transfer-proficient bacteria and a potential recipient initiate a cascade of transfer which can continue until all potential recipients have acquired the plasmid. Other systems express their transfer genes in response to specific stimuli. For the pheromone-responsive plasmids of Enterococcus it is small peptide signals from potential recipients which trigger the conjugative transfer genes. For the Ti plasmids of Agrobacterium it is the presence of wounded plants which are susceptible to infection which stimulates T-DNA transfer to plants. Transfer and integration of T-DNA induces production of opines which the plasmid-positive bacteria can utilise. They multiply and when they reach an appropriate density their plasmid transfer system is switched on to allow transfer of the Ti plasmid to other bacteria. Finally some conjugative transfer systems are induced by the antibiotics to which the elements confer resistance. Understanding these control circuits may help to modify management of microbial communities where plasmid transfer is either desirable or undesirable. z 1998 Published by Elsevier Science B.V. | 1998 | 25508777 |
| 9850 | 13 | 0.9997 | Annotation 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. | 2024 | 38819561 |
| 9851 | 14 | 0.9997 | The potential of integrons and connected programmed rearrangements for mediating horizontal gene transfer. Site-specific recombination of integrons, mediates transfer of single genes in small genomes and plasmids. Recent data suggest that new genes are recruited to the cassettes--the units moved by integrons. Integrons are resident in a class of transposons with pronounced target selectivity for resolution loci in broad host range plasmids. A resulting network of programmed transfer routes, with potential offshoots reaching into eukaryotic cells, may channel genes to unexpectedly remote organisms. It has previously been observed that the conjugation apparatus of the broad host range plasmid R751 (IncP) which contains transposon Tn5090 harbouring an integron, promotes horizontal genetic transfer between bacteria and yeast. Furthermore, it is well known and fundamental for widely used gene replacement technologies, that site-specific recombination systems (e.g. Cre-lox of bacteriophage P1) related to the integrons are functional in higher eukaryotes. It seems very clear that integrons and associated programmed transfer mechanisms have high significance for the dissemination of antibiotic resistance genes in bacteria whereas further studies are needed to assess their importance for spreading of arbitrary genes in a wider range of host systems. | 1998 | 9850680 |
| 9350 | 15 | 0.9997 | Genome DNA Sequence Variation, Evolution, and Function in Bacteria and Archaea. Comparative genomics has revealed that variations in bacterial and archaeal genome DNA sequences cannot be explained by only neutral mutations. Virus resistance and plasmid distribution systems have resulted in changes in bacterial and archaeal genome sequences during evolution. The restriction-modification system, a virus resistance system, leads to avoidance of palindromic DNA sequences in genomes. Clustered, regularly interspaced, short palindromic repeats (CRISPRs) found in genomes represent yet another virus resistance system. Comparative genomics has shown that bacteria and archaea have failed to gain any DNA with GC content higher than the GC content of their chromosomes. Thus, horizontally transferred DNA regions have lower GC content than the host chromosomal DNA does. Some nucleoid-associated proteins bind DNA regions with low GC content and inhibit the expression of genes contained in those regions. This form of gene repression is another type of virus resistance system. On the other hand, bacteria and archaea have used plasmids to gain additional genes. Virus resistance systems influence plasmid distribution. Interestingly, the restriction-modification system and nucleoid-associated protein genes have been distributed via plasmids. Thus, GC content and genomic signatures do not reflect bacterial and archaeal evolutionary relationships. | 2013 | 22772895 |
| 9314 | 16 | 0.9997 | Phage Transduction of Staphylococcus aureus. Bacteriophage transduction is the major mechanism of horizontal gene transfer (HGT) among many bacteria. In Staphylococcus aureus, the phage-mediated acquisition of mobile genetic elements (MGEs) that encode virulence and antibiotic resistance genes largely contribute to its evolutionary adaptation and genetic plasticity. In molecular biology, generalized transduction is routinely used as a technique to manipulate and construct bacterial strains. Here, we describe optimized protocols for generalized transduction, applicable for the transfer of plasmid or chromosomal deoxyribonucleic acid (DNA) from donor to recipient S. aureus strains. | 2024 | 37966605 |
| 9304 | 17 | 0.9997 | Variation of the flagellin gene locus of Campylobacter jejuni by recombination and horizontal gene transfer. The capacity of Campylobacter jejuni to generate genetic diversity was determined for its flagellar region. Recombination within a genome, as well as recombination after the uptake of exogenous DNA, could be demonstrated. The subunit of the flagellar filament of C. jejuni is encoded by two tandem genes, flaA and flaB, which are highly similar and therefore subject to recombination. A spontaneous recombination within this locus was demonstrated in a bacterial clone containing an antibiotic-resistance gene inserted in flaA. A recombinant was isolated in which the antibiotic-resistance gene had been repositioned into flaB, indicating that genetic information can be exchanged between the two flagellin genes of C. jejuni. The occurrence of recombinational events after the uptake of exogenous DNA by naturally competent bacteria was demonstrated with two mutants containing different antibiotic-resistance markers in their flagellin genes. Double-resistant transformants were formed when purified chromosomal donor DNA was added to a recipient strain, when the two bacterial cultures were mixed under conditions that induce natural competence, or when the two strains were cocultured. Both mechanisms of recombination may be used by the pathogenic organism to escape the immunological responses of the host or otherwise adapt to the environment. | 1995 | 7894725 |
| 9845 | 18 | 0.9997 | Mobile antibiotic resistance encoding elements promote their own diversity. Integrating conjugative elements (ICEs) are a class of bacterial mobile genetic elements that disseminate via conjugation and then integrate into the host cell genome. The SXT/R391 family of ICEs consists of more than 30 different elements that all share the same integration site in the host chromosome but often encode distinct properties. These elements contribute to the spread of antibiotic resistance genes in several gram-negative bacteria including Vibrio cholerae, the agent of cholera. Here, using comparative analyses of the genomes of several SXT/R391 ICEs, we found evidence that the genomes of these elements have been shaped by inter-ICE recombination. We developed a high throughput semi-quantitative method to explore the genetic determinants involved in hybrid ICE formation. Recombinant ICE formation proved to be relatively frequent, and to depend on host (recA) and ICE (s065 and s066) loci, which can independently and potentially cooperatively mediate hybrid ICE formation. s065 and s066, which are found in all SXT/R391 ICEs, are orthologues of the bacteriophage lambda Red recombination genes bet and exo, and the s065/s066 recombination system is the first Red-like recombination pathway to be described in a conjugative element. Neither ICE excision nor conjugative transfer proved to be essential for generation of hybrid ICEs. Instead conjugation facilitates the segregation of hybrids and could provide a means to select for functional recombinant ICEs containing novel combinations of genes conferring resistance to antibiotics. Thus, ICEs promote their own diversity and can yield novel mobile elements capable of disseminating new combinations of antibiotic resistance genes. | 2009 | 20019796 |
| 3837 | 19 | 0.9997 | 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 |