The Tn21 subgroup of bacterial transposable elements. - Related Documents




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982001.0000The Tn21 subgroup of bacterial transposable elements. The Tn3 family of transposable elements is probably the most successful group of mobile DNA elements in bacteria: there are many different but related members and they are widely distributed in gram-negative and gram-positive bacteria. The Tn21 subgroup of the Tn3 family contains closely related elements that provide most of the currently known variation in Tn3-like elements in gram-negative bacteria and that are largely responsible for the problem of multiple resistance to antibiotics in these organisms. This paper reviews the structure, the mechanism of transposition, the mode of acquisition of accessory genes, and the evolution of these elements.19901963947
981910.9999Site-specific recombination and shuffling of resistance genes in transposon Tn21. Many multidrug-resistant transposons found in natural isolates of Gram-negative bacteria are close relatives of Tn21. Thus, the Tn21 subgroup of the Tn3 family of transposable elements is the most successful homogeneous group in acquiring resistance to newly introduced antibiotics. This paper summarizes the mode of acquisition of resistance genes by these elements.19911660178
982220.9999Molecular 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.19873035697
982130.9998Mercury resistance (mer) operons in enterobacteria. Mercury resistance is found in many genera of bacteria. Common amongst enterobacteria are transposons related to Tn21, which is both mercuric ion- and streptomycin-/spectinomycin- and sulphonamide-resistant. Other Tn21-related transposons often have different antibiotic resistances compared with Tn21, but share many non-antibiotic-resistance genes with it. In this article we discuss possible mechanisms for the evolution of Tn21 and related genetic elements.200212196175
446840.9998Mobile gene cassettes and integrons: moving antibiotic resistance genes in gram-negative bacteria. In Gram-negative pathogens, multiple antibiotic resistance is common and many of the known resistance genes are contained in mobile gene cassettes. Cassettes can be integrated into or deleted from their receptor elements, the integrons, or infrequently may be integrated at other locations via site-specific recombination catalysed by an integron-encoded recombinase. As a consequence, arrays of several different antibiotic resistance genes can be created. Over 40 gene cassettes and three distinct classes of integrons have been identified to date. Cassette-associated genes conferring resistance to beta-lactams, aminoglycosides, trimethoprim, chloramphenicol, streptothricin and quaternary ammonium compounds used as antiseptics and disinfectants have been found. In addition, most members of the commonest family of integrons (class 1) include a sulfonamide resistance determinant in the backbone structure. Integrons are themselves translocatable, though most are defective transposon derivatives. Integron movement allows transfer of the cassette-associated resistance genes from one replicon to another or into another active transposon which facilitates spread of integrons that are transposition defective. Horizontal transfer of the resistance genes can be achieved when an integron containing one or more such genes is incorporated into a broad-host-range plasmid. Likewise, single cassettes integrated at secondary sites in a broad-host-range plasmid can also move across species boundaries.19979189642
446950.9998Integrons: an antibiotic resistance gene capture and expression system. Bacteria can transfer genetic information to provide themselves with protection against most antibiotics. The acquisition of resistance gene arrays involves genetic mobile elements like plasmids and transposons. Another class of genetic structures, termed integrons, have been described and contain one or more gene cassettes located at a specific site. Integrons are defined by an intl gene encoding an integrase, a recombination site attl and a strong promoter. At least six classes of integrons have been determined according to their intl gene. Classes 1, 2 and 3 are the most studied and are largely implicated in the dissemination of antibiotic resistance. A gene cassette includes an open reading frame and, at the 3'-end, a recombination site attC. Integration or excision of cassettes occur by a site-specific recombination mechanism catalyzed by the integrase. However, insertion can occur, albeit rarely, at non-specific sites leading to a stable situation for the cassette. Cassettes are transcribed from the common promoter located in the 5'-conserved segment and expression of distal genes is reduced by the presence of upstream cassettes. Most gene cassettes encode antibiotic resistant determinants but antiseptic resistant genes have also been described. Integrons seem to have a major role in the spread of multidrug resistance in gram-negative bacteria but integrons in gram-positive bacteria were described recently. Moreover, the finding of super-integrons with gene-cassettes coding for other determinants (biochemical functions, virulence factors) in Vibrio isolates dating from 1888 suggests the likely implication of this multicomponent cassette-integron system in bacterial genome evolution before the antibiotic era and to a greater extent than initially believed.200010987194
982560.9998Intercontinental spread of promiscuous mercury-resistance transposons in environmental bacteria. We demonstrate that horizontal spread of mer operons similar to worldwide spread of antibiotic-resistance genes in medically important bacteria occurred in bacteria found in ores, soils and waters. The spread was mediated by different transposons and plasmids. Some of the spreading transposons were damaged in different ways but this did not prevent their further spread. Certain transposons are mosaics composed of segments belonging to distinct sequence types. These mosaics arose as a result of homologous and site-specific recombination. Our data suggest that the mercury-resistance operons of Gram-negative environmental bacteria can be considered as a worldwide population composed of a relatively small number of distinct recombining clones shared, at least partially, by environmental and clinical bacteria.19979159519
982370.9998Transposition of an antibiotic resistance element in mycobacteria. Bacterial resistance to antibiotics is often plasmid-mediated and the associated resistance genes encoded by transposable elements. Mycobacteria, including the human pathogens Mycobacterium tuberculosis and M. leprae, are resistant to many antibiotics, and their cell-surface structure is believed to be largely responsible for the wide range of resistance phenotypes. Antibiotic-resistance plasmids have so far not been implicated in resistance of mycobacteria to antibiotics. Nevertheless, antibiotic-modifying activities such as aminoglycoside acetyltransferases and phosphotransferases have been detected in fast-growing species. beta-lactamases have also been found in most fast- and slow-growing mycobacteria. To date no mycobacterial antibiotic-resistance genes have been isolated and characterized. We now report the isolation, cloning and sequencing of a genetic region responsible for resistance to sulphonamides in M. fortuitum. This region also contains an open reading frame homologous to one present in Tn1696 (member of the Tn21 family) which encodes a site-specific integrase. The mycobacterial resistance element is flanked by repeated sequences of 880 base pairs similar to the insertion elements of the IS6 family found in Gram+ and Gram- bacteria. The insertion element is shown to transpose to different sites in the chromosome of a related fast-growing species, M. smegmatis. The characterization of this element should permit transposon mutagenesis in the analysis of mycobacterial virulence and related problems.19902163027
986780.9998Mosaic plasmids are abundant and unevenly distributed across prokaryotic taxa. Mosaic plasmids, plasmids composed of genetic elements from distinct sources, are associated with the spread of antibiotic resistance genes. Transposons are considered the primary mechanism for mosaic plasmid formation, though other mechanisms have been observed in specific instances. The frequency with which mosaic plasmids have been described suggests they may play an important role in plasmid population dynamics. Our survey of the confirmed plasmid sequences available from complete and draft genomes in the RefSeq database shows that 46% of them fit a strict definition of mosaic. Mosaic plasmids are also not evenly distributed over the taxa represented in the database. Plasmids from some genera, including Piscirickettsia and Yersinia, are almost all mosaic, while plasmids from other genera, including Borrelia, are rarely mosaic. While some mosaic plasmids share identical regions with hundreds of others, the median mosaic plasmid only shares with 8 other plasmids. When considering only plasmids from finished genomes (51.6% of the total), mosaic plasmids have significantly higher proportions of transposase and antibiotic resistance genes. Conversely, only 56.6% of mosaic fragments (DNA fragments shared between mosaic plasmids) contain a recognizable transposase gene, and only 1.2% of mosaic fragments are flanked by inverted repeats. Mosaic fragments associated with the IS26 transposase gene are 3.8-fold more abundant than any other sequence shared between mosaic plasmids in the database, though this is at least partly due to overrepresentation of Enterobacteriaceae plasmids. Mosaic plasmids are a complicated trait of some plasmid populations, only partly explained by transposition. Though antibiotic resistance genes led to the identification of many mosaic plasmids, mosaic plasmids are a broad phenomenon encompassing many more traits than just antibiotic resistance. Further research will be required to determine the influence of ecology, host repair mechanisms, conjugation, and plasmid host range on the formation and influence of mosaic plasmids. AUTHOR SUMMARY: Plasmids are extrachromosomal genetic entities that are found in many prokaryotes. They serve as flexible storage for genes, and individual cells can make substantial changes to their characteristics by acquiring, losing, or modifying a plasmid. In some pathogenic bacteria, such as Escherichia coli, antibiotic resistance genes are known to spread primarily on plasmids. By analyzing a database of 8592 plasmid sequences we determined that many of these plasmids have exchanged genes with each other, becoming mosaics of genes from different sources. We next separated these plasmids into groups based on the organism they were isolated from and found that different groups had different fractions of mosaic plasmids. This result was unexpected and suggests that the mechanisms and selective pressures causing mosaic plasmids do not occur evenly over all species. It also suggests that plasmids may provide different levels of potential variation to different species. This work uncovers a previously unrecognized pattern in plasmids across prokaryotes, that could lead to new insights into the evolutionary role that plasmids play.201930797764
983090.9998Mechanisms 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.201729536357
9307100.9998Integrons. 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.201020707672
4163110.9998The 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
4164120.9998Broad-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
9824130.9998Transposons: the agents of antibiotic resistance in bacteria. Transposons are a group of mobile genetic elements that are defined as a DNA sequence. Transposons can jump into different places of the genome; for this reason, they are called jumping genes. However, some transposons are always kept at the insertion site in the genome. Most transposons are inactivated and as a result, cannot move. Transposons are divided into two main groups: retrotransposons (class І) and DNA transposons (class ІІ). Retrotransposons are often found in eukaryotes. DNA transposons can be found in both eukaryotes and prokaryotes. The bacterial transposons belong to the DNA transposons and the Tn family, which are usually the carrier of additional genes for antibiotic resistance. Transposons can transfer from a plasmid to other plasmids or from a DNA chromosome to plasmid and vice versa that cause the transmission of antibiotic resistance genes in bacteria. The treatment of bacterial infectious diseases is difficult because of existing antibiotic resistance that part of this antibiotic resistance is caused by transposons. Bacterial infectious diseases are responsible for the increasing rise in world mortality rate. In this review, transposons and their roles have been studied in bacterial antibiotic resistance, in detail.201830113080
4467140.9998PCR mapping of integrons reveals several novel combinations of resistance genes. The integron is a new type of mobile element which has evolved by a site-specific recombinational mechanism. Integrons consist of two conserved segments of DNA separated by a variable region containing one or more genes integrated as cassettes. Oligonucleotide probes specific for the conserved segments have revealed that integrons are widespread in recently isolated clinical bacteria. Also, by using oligonucleotide probes for several antibiotic resistance genes, we have found novel combinations of resistance genes in these strains. By using PCR, we have determined the content and order of the resistance genes inserted between the conserved segments in the integrons of these clinical isolates. PCR mapping of integrons can be a useful epidemiological tool to study the evolution of multiresistance plasmids and transposons and dissemination of antibiotic resistance genes.19957695304
4165150.9998A 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
9847160.9998Comparative ICE genomics: insights into the evolution of the SXT/R391 family of ICEs. Integrating and conjugative elements (ICEs) are one of the three principal types of self-transmissible mobile genetic elements in bacteria. ICEs, like plasmids, transfer via conjugation; but unlike plasmids and similar to many phages, these elements integrate into and replicate along with the host chromosome. Members of the SXT/R391 family of ICEs have been isolated from several species of gram-negative bacteria, including Vibrio cholerae, the cause of cholera, where they have been important vectors for disseminating genes conferring resistance to antibiotics. Here we developed a plasmid-based system to capture and isolate SXT/R391 ICEs for sequencing. Comparative analyses of the genomes of 13 SXT/R391 ICEs derived from diverse hosts and locations revealed that they contain 52 perfectly syntenic and nearly identical core genes that serve as a scaffold capable of mobilizing an array of variable DNA. Furthermore, selection pressure to maintain ICE mobility appears to have restricted insertions of variable DNA into intergenic sites that do not interrupt core functions. The variable genes confer diverse element-specific phenotypes, such as resistance to antibiotics. Functional analysis of a set of deletion mutants revealed that less than half of the conserved core genes are required for ICE mobility; the functions of most of the dispensable core genes are unknown. Several lines of evidence suggest that there has been extensive recombination between SXT/R391 ICEs, resulting in re-assortment of their respective variable gene content. Furthermore, our analyses suggest that there may be a network of phylogenetic relationships among sequences found in all types of mobile genetic elements.200920041216
9827170.9998Evolution of bacterial resistance to antibiotics during the last three decades. Bacterial resistance to antibiotics is often plasmid-mediated and the associated genes encoded by transposable elements. These elements play a central role in evolution by providing mechanisms for the generation of diversity and, in conjunction with DNA transfer systems, for the dissemination of resistances to other bacteria. At the University Hospital of Zaragoza, extensive efforts have been made to define both the dissemination and evolution of antibiotic resistance by studying the transferable R plasmids and transposable elements. Here we describe the research on bacterial resistance to antibiotics in which many authors listed in the references have participated. The aspects of bacterial resistance dealt with are: (i) transferable resistance mediated by R plasmids in Gram-negative bacteria, (ii) R plasmid-mediated resistance to apramycin and hygromycin in clinical strains, (iii) the transposon Tn1696 and the integron In4, (iv) expression of Escherichia coli resistance genes in Haemophilus influenzae, (v) aminoglycoside-modifying-enzymes in the genus Mycobacterium with no relation to resistance, and (vi) macrolide-resistance and new mechanisms developed by Gram-positive bacteria.199810943375
4134180.9998Plasmid-Mediated Antimicrobial Resistance in Staphylococci and Other Firmicutes. In staphylococci and other Firmicutes, resistance to numerous classes of antimicrobial agents, which are commonly used in human and veterinary medicine, is mediated by genes that are associated with mobile genetic elements. The gene products of some of these antimicrobial resistance genes confer resistance to only specific members of a certain class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents. The resistance mechanisms specified by the resistance genes fall into any of three major categories: active efflux, enzymatic inactivation, and modification/replacement/protection of the target sites of the antimicrobial agents. Among the mobile genetic elements that carry such resistance genes, plasmids play an important role as carriers of primarily plasmid-borne resistance genes, but also as vectors for nonconjugative and conjugative transposons that harbor resistance genes. Plasmids can be exchanged by horizontal gene transfer between members of the same species but also between bacteria belonging to different species and genera. Plasmids are highly flexible elements, and various mechanisms exist by which plasmids can recombine, form cointegrates, or become integrated in part or in toto into the chromosomal DNA or into other plasmids. As such, plasmids play a key role in the dissemination of antimicrobial resistance genes within the gene pool to which staphylococci and other Firmicutes have access. This chapter is intended to provide an overview of the current knowledge of plasmid-mediated antimicrobial resistance in staphylococci and other Firmicutes.201426104453
9828190.9998Antibiotic resistance: genetic mechanisms and mobility. Based on the current knowledge, resistance genes seems mainly to originate in the organisms which produce antibiotics (Davies 1994). We lack considerably in the understanding of how these genes were transferred to pathogenic bacteria, and due to the enormous diversity of e.g. the soil flora, it is doubtful that we will ever obtain more that a faint picture of this. In Gram negative bacteria, more and more resistance genes are demonstrated to be located in integrons (e.g. beta-lactamase and streptomycin resistance genes in Salmonella Typhimurium DT104 (Sandvang et al. in press)). Integrons seem primarily to act as insertion sites for resistance genes. The origin of integrons as well as the resistance gene cassettes that are the other essential element of this system, is largely unknown (Hall & Collis 1995). Integrons can be located in the chromosome, in transposons, which have the ability to copy them themselves to other DNA molecules, or on plasmids. The emergence of resistant bacteria normally happens because of selection for a resistant clone of bacteria. Several mechanisms, however, exists by which the resistance genes can be transferred from one bacteria to another. Conjugation, mediated by plasmids or conjugative transposons, is currently the most well established of these mechanisms. Still, however, the selection pressure created by the use of antibiotics determines whether bacteria that have newly acquired a resistance gene expand to dominate in the population or remains a blink in history.199910783713