Mobilization of transposons : rationale and techniques for detection. - Related Documents




#
Rank
Similarity
Title + Abs.
Year
PMID
012345
413201.0000Mobilization of transposons : rationale and techniques for detection. The ability to share genetic information with other bacteria represents one of the most important adaptive mechanisms available to bacteria pathogenic for humans. The exchange of many different types of genetic information appears to occur frequently and exchange of determinants responsible for antimicrobial resistance is the best studied, since the movements of resistance determinants are easy to follow and the clinical importance of resistance dissemination is so great. The most common vehicles by which bacteria exchange resistance determinants are plasmids and transposons.200121374427
413410.9999Plasmid-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
413320.9999Importance 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
990730.9999Mobile Genetic Elements Associated with Antimicrobial Resistance. Strains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool. This is achieved through the concerted activities of mobile genetic elements able to move within or between DNA molecules, which include insertion sequences, transposons, and gene cassettes/integrons, and those that are able to transfer between bacterial cells, such as plasmids and integrative conjugative elements. Together these elements play a central role in facilitating horizontal genetic exchange and therefore promote the acquisition and spread of resistance genes. This review aims to outline the characteristics of the major types of mobile genetic elements involved in acquisition and spread of antibiotic resistance in both Gram-negative and Gram-positive bacteria, focusing on the so-called ESKAPEE group of organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli), which have become the most problematic hospital pathogens.201830068738
988140.9999Plasmids and the spread of resistance. Plasmids represent one of the most difficult challenge for counteracting the dissemination of antimicrobial resistance. They contribute to the spread of relevant resistance determinants, promoting horizontal gene transfer among unrelated bacteria. Undistinguishable plasmids were identified in unrelated bacterial strains isolated at huge geographically distant area, with no apparent epidemiological links. These plasmids belong to families that are largely prevalent in naturally occurring bacteria, usually carry multiple physically linked genetic determinants, conferring resistance to different classes of antibiotics simultaneously. Plasmids also harbour virulence factors and addiction systems, promoting their stability and maintenance in the bacterial host, in different environmental conditions. The characteristics of the most successful plasmids that were at the origin of the spread of carbapenemase, expanded-spectrum β-lactamase, and plasmid-mediated quinolone resistance genes are discussed in this review.201323499304
414250.9999Antimicrobial Resistance in Pasteurellaceae of Veterinary Origin. Members of the highly heterogeneous family Pasteurellaceae cause a wide variety of diseases in humans and animals. Antimicrobial agents are the most powerful tools to control such infections. However, the acquisition of resistance genes, as well as the development of resistance-mediating mutations, significantly reduces the efficacy of the antimicrobial agents. This article gives a brief description of the role of selected members of the family Pasteurellaceae in animal infections and of the most recent data on the susceptibility status of such members. Moreover, a review of the current knowledge of the genetic basis of resistance to antimicrobial agents is included, with particular reference to resistance to tetracyclines, β-lactam antibiotics, aminoglycosides/aminocyclitols, folate pathway inhibitors, macrolides, lincosamides, phenicols, and quinolones. This article focusses on the genera of veterinary importance for which sufficient data on antimicrobial susceptibility and the detection of resistance genes are currently available (Pasteurella, Mannheimia, Actinobacillus, Haemophilus, and Histophilus). Additionally, the role of plasmids, transposons, and integrative and conjugative elements in the spread of the resistance genes within and beyond the aforementioned genera is highlighted to provide insight into horizontal dissemination, coselection, and persistence of antimicrobial resistance genes. The article discusses the acquisition of diverse resistance genes by the selected Pasteurellaceae members from other Gram-negative or maybe even Gram-positive bacteria. Although the susceptibility status of these members still looks rather favorable, monitoring of their antimicrobial susceptibility is required for early detection of changes in the susceptibility status and the newly acquired/developed resistance mechanisms.201829916344
988260.9999Integrons in Enterobacteriaceae: diversity, distribution and epidemiology. Integrons are versatile gene acquisition systems that allow efficient capturing of exogenous genes and ensure their expression. Various classes of integrons possessing a wide variety of gene cassettes are ubiquitously distributed in enteric bacteria worldwide. The epidemiology of integrons associated multidrug resistance in Enterobacteriaceae is rapidly evolving. In the past two decades, the incidence of integrons in enteric bacteria has increased drastically with evolution of multiple gene cassettes, novel gene arrangements and complex chromosomal integrons such as Salmonella genomic islands. This review focuses on the distribution, versatility, spread and global trends of integrons among important members of the Enterobacteriaceae, including Escherichia coli, Klebsiella, Shigella and Salmonella, which are known to cause infections globally. Such a comprehensive understanding of integron-associated antibiotic resistance, their role in the spread of such resistance traits and their clinical relevance especially with regard to each genus individually is paramount to contain the global spread of antibiotic resistance.201829038087
447270.9998Conjugative plasmids in bacteria of the 'pre-antibiotic' era. Antibiotic resistance is common in bacteria that cause disease in man and animals and is usually determined by plasmids. The prevalence of such plasmids, and the range of drugs to which they confer resistance, have increased greatly in the past 25 yr. It has become clear from work in many laboratories that plasmids have acquired resistance genes, of ultimately unknown origin, as insertions into their circular DNA. The intensive use of antibiotics since their introduction in the 1940s can explain the spread of plasmids that have acquired such genes but little is known of the incidence of plasmids in pathogenic bacteria before the widespread use of antibiotics in medicine. E.D.G. Murray collected strains of Enterobacteriaceae from 1917 to 1954; we now report that 24% of these encode information for the transfer of DNA from one bacterium to another. From at least 19% of the strains, conjugative plasmids carrying no antibiotic resistance were transferred to Escherichia coli K-12.19836835408
417280.9998Variation on a theme; an overview of the Tn916/Tn1545 family of mobile genetic elements in the oral and nasopharyngeal streptococci. The oral and nasopharyngeal streptococci are a major part of the normal microbiota in humans. Most human associated streptococci are considered commensals, however, a small number of them are pathogenic, causing a wide range of diseases including oral infections such as dental caries and periodontitis and diseases at other body sites including sinusitis and endocarditis, and in the case of Streptococcus pneumoniae, meningitis. Both phenotypic and sequence based studies have shown that the human associated streptococci from the mouth and nasopharynx harbor a large number of antibiotic resistance genes and these are often located on mobile genetic elements (MGEs) known as conjugative transposons or integrative and conjugative elements of the Tn916/Tn1545 family. These MGEs are responsible for the spread of the resistance genes between streptococci and also between streptococci and other bacteria. In this review we describe the resistances conferred by, and the genetic variations between the many different Tn916-like elements found in recent studies of oral and nasopharyngeal streptococci and show that Tn916-like elements are important mediators of antibiotic resistance genes within this genus. We will also discuss the role of the oral environment and how this is conducive to the transfer of these elements and discuss the contribution of both transformation and conjugation on the transfer and evolution of these elements in different streptococci.201425368607
431290.9998Genes and mutations conferring antimicrobial resistance in Salmonella: an update. Resistance to various classes of antimicrobial agents has been encountered in many bacteria of medical and veterinary relevance. Particular attention has been paid to zoonotic bacteria such as Salmonella. Over the years, various studies have reported the presence of genes and mutations conferring resistance to antimicrobial agents in Salmonella isolates. This review is intended to provide an update on what is currently known about the genetic basis of antimicrobial resistance in Salmonella.200616716631
4149100.9998Antibiotic resistance genes from the environment: a perspective through newly identified antibiotic resistance mechanisms in the clinical setting. Soil bacteria may contain antibiotic resistance genes responsible for different mechanisms that permit them to overcome the natural antibiotics present in the environment. This gene pool has been recently named the 'resistome', and its components can be mobilized into the microbial community affecting humans because of the participation of genetic platforms that efficiently facilitate the mobilization and maintenance of these resistance genes. Evidence for this transference has been suggested or demonstrated with newly identified widespread genes in multidrug-resistant bacteria. These resistance genes include those responsible for ribosomal methylases affecting aminoglycosides (armA, rtmB), methyltransferases affecting linezolid (cfr) or plasmid-mediated efflux pumps conferring low-level fluoroquinolone resistance (qepA), all of which are associated with antibiotic-producing bacteria. In addition, resistance genes whose ancestors have been identified in environmental isolates that are not recognized as antibiotic producers have also been recently detected. These include the qnr and the bla(CTX) genes compromising the activity of fluoroquinolones and extended-spectrum cephalosporins, respectively. The application of metagenomic tools and phylogenetic analysis will facilitate future identification of other new resistance genes and their corresponding ancestors in environmental bacteria, and will enable further exploration of the concept of the resistome as being a unique reservoir of antibiotic resistance genes and genetic elements participating in resistance gene transfer.200919220348
4145110.9998Antimicrobial Resistance among Staphylococci of Animal Origin. Antimicrobial resistance among staphylococci of animal origin is based on a wide variety of resistance genes. These genes mediate resistance to many classes of antimicrobial agents approved for use in animals, such as penicillins, cephalosporins, tetracyclines, macrolides, lincosamides, phenicols, aminoglycosides, aminocyclitols, pleuromutilins, and diaminopyrimidines. In addition, numerous mutations have been identified that confer resistance to specific antimicrobial agents, such as ansamycins and fluoroquinolones. The gene products of some of these resistance genes confer resistance to only specific members of a class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents, including agents approved solely for human use. The resistance genes code for all three major resistance mechanisms: enzymatic inactivation, active efflux, and protection/modification/replacement of the cellular target sites of the antimicrobial agents. Mobile genetic elements, in particular plasmids and transposons, play a major role as carriers of antimicrobial resistance genes in animal staphylococci. They facilitate not only the exchange of resistance genes among members of the same and/or different staphylococcal species, but also between staphylococci and other Gram-positive bacteria. The observation that plasmids of staphylococci often harbor more than one resistance gene points toward coselection and persistence of resistance genes even without direct selective pressure by a specific antimicrobial agent. This chapter provides an overview of the resistance genes and resistance-mediating mutations known to occur in staphylococci of animal origin.201829992898
4313120.9998Molecular epidemiology of clinically significant antibiotic resistance genes. Antimicrobials were first introduced into medical practice a little over 60 years ago and since that time resistant strains of bacteria have arisen in response to the selective pressure of their use. This review uses the paradigm of the evolution and spread of beta-lactamases and in particular beta-lactamases active against antimicrobials used to treat Gram-negative infections. The emergence and evolution particularly of CTX-M extended-spectrum beta-lactamases (ESBLs) is described together with the molecular mechanisms responsible for both primary mutation and horizontal gene transfer. Reference is also made to other significant antibiotic resistance genes, resistance mechanisms in Gram-negative bacteria, such as carbepenamases, and plasmid-mediated fluoroquinolone resistance. The pathogen Staphylococcus aureus is reviewed in detail as an example of a highly successful Gram-positive bacterial pathogen that has acquired and developed resistance to a wide range of antimicrobials. The role of selective pressures in the environment as well as the medical use of antimicrobials together with the interplay of various genetic mechanisms for horizontal gene transfer are considered in the concluding part of this review.200818311156
9910130.9998Plasmid-Mediated Antibiotic Resistance and Virulence in Gram-Negatives: the Klebsiella pneumoniae Paradigm. Plasmids harbor genes coding for specific functions including virulence factors and antibiotic resistance that permit bacteria to survive the hostile environment found in the host and resist treatment. Together with other genetic elements such as integrons and transposons, and using a variety of mechanisms, plasmids participate in the dissemination of these traits, resulting in the virtual elimination of barriers among different kinds of bacteria. In this article we review the current information about the physiology of plasmids and their role in virulence and antibiotic resistance from the Gram-negative opportunistic pathogen Klebsiella pneumoniae. This bacterium has acquired multidrug resistance and is the causative agent of serious community- and hospital-acquired infections. It is also included in the recently defined ESKAPE group of bacteria that cause most U.S. hospital infections.201426104358
4131140.9998R plasmid transfer. This paper is a brief survey of the systems of genetic exchange in bacteria relevant to the spread of antibiotic resistance genes. Emphasis is given to those systems most likely to be important in nature, particularly conjugation. Several recently described examples of conjugation in Gram-positive bacteria are discussed and contrasted with the better studied examples in Gram-negative bacteria.19863542931
4045150.9998Bacterial resistance to antimicrobial agents and its impact on veterinary and human medicine. BACKGROUND: Antimicrobial resistance has become a major challenge in veterinary medicine, particularly in the context of bacterial pathogens that play a role in both humans and animals. OBJECTIVES: This review serves as an update on acquired resistance mechanisms in bacterial pathogens of human and animal origin, including examples of transfer of resistant pathogens between hosts and of resistance genes between bacteria. RESULTS: Acquired resistance is based on resistance-mediating mutations or on mobile resistance genes. Although mutations are transferred vertically, mobile resistance genes are also transferred horizontally (by transformation, transduction or conjugation/mobilization), contributing to the dissemination of resistance. Mobile genes specifying any of the three major resistance mechanisms - enzymatic inactivation, reduced intracellular accumulation or modification of the cellular target sites - have been found in a variety of bacteria that may be isolated from animals. Such resistance genes are associated with plasmids, transposons, gene cassettes, integrative and conjugative elements or other mobile elements. Bacteria, including zoonotic pathogens, can be exchanged between animals and humans mainly via direct contact, but also via dust, aerosols or foods. Proof of the direction of transfer of resistant bacteria can be difficult and depends on the location of resistance genes or mutations in the chromosomal DNA or on a mobile element. CONCLUSION: The wide variety in resistance and resistance transfer mechanisms will continue to ensure the success of bacterial pathogens in the future. Our strategies to counteract resistance and preserve the efficacy of antimicrobial agents need to be equally diverse and resourceful.201727581211
4151160.9998Evolutionary relationships among genes for antibiotic resistance. The genes that determine resistance to antibiotics are commonly found encoded by extrachromosomal elements in bacteria. These were described first in Enterobacteriaceae and subsequently in a variety of other genera; their spread is associated with the increased use of antibiotics in human and animal medicine. Antibiotic-resistance genes that determine the production of enzymes which modify (detoxify) the antibiotics have been detected in antibiotic-producing organisms. It has been suggested that the producing strains provided the source of antibiotic-resistance genes that were then 'picked-up' by recombination. Recent studies of the nucleotide sequence of certain antibiotic-resistance genes indicate regions of strong homology in the encoded proteins. The implications of these similarities are discussed.19846559117
3834170.9998What antimicrobial resistance has taught us about horizontal gene transfer. Horizontal gene transfer (HGT) has been responsible for the dissemination of numerous antimicrobial-resistance determinants throughout diverse bacterial species. The rapid and broad dissemination of resistance determinants by HGT, and subsequent selection for resistance imposed by the use of antimicrobials, threatens to undermine the usefulness of antimicrobials. However, vigilant surveillance of the emerging antimicrobial resistance in clinical settings and subsequent studies of resistant isolates create a powerful system for studying HGT and detecting rare events. Two of the most closely monitored phenotypes are resistance to beta-lactams and resistance to fluoroquinolones. Studies of resistance to these antimicrobials have revealed that (1) transformation occurs between different species of bacteria including some recipient species that were not previously known to be competent for natural transformation; (2) transduction may be playing an important role in generating novel methicillin-resistant Staphylococcus aureus (MRSA) strains, although the details of transferring the SCCmec element are not yet fully understood; (3) Resistance genes are probably moving to plasmids from chromosomes more rapidly than in the past; and (4) Resistance genes are aggregating upon plasmids. The linkage of numerous resistance genes on individual plasmids may underlie the persistence of resistance to specific antimicrobials even when use of those antimicrobials is discontinued. Further studies of HGT and methods for controlling HGT may be necessary to maintain the usefulness of antimicrobials.200919271198
9894180.9998Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids. The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content) of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE) from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance. IMPORTANCE: The spread of antibiotic resistance among Gram-negative bacteria is a serious public health threat, as it can critically limit the types of drugs that can be used to treat infected patients. In particular, carbapenem-resistant members of the Enterobacteriaceae family are responsible for a significant and growing burden of morbidity and mortality. Here, we report on the mechanisms underlying the evolution of several plasmids carried by previously sequenced clinical Enterobacteriaceae isolates from the National Institutes of Health Clinical Center (NIH CC). Our ability to track genetic rearrangements that occurred within resistance plasmids was dependent on accurate annotation of the mobile genetic elements within the plasmids, which was greatly aided by access to long-read DNA sequencing data and knowledge of their mechanisms. Mobile genetic elements such as transposons and integrons have been strongly associated with the rapid spread of genes responsible for antibiotic resistance. Understanding the consequences of their actions allowed us to establish unambiguous evolutionary relationships between plasmids in the analysis set.201627923922
4423190.9998Inactivation of antibiotics and the dissemination of resistance genes. The emergence of multidrug-resistant bacteria is a phenomenon of concern to the clinician and the pharmaceutical industry, as it is the major cause of failure in the treatment of infectious diseases. The most common mechanism of resistance in pathogenic bacteria to antibiotics of the aminoglycoside, beta-lactam (penicillins and cephalosporins), and chloramphenicol types involves the enzymic inactivation of the antibiotic by hydrolysis or by formation of inactive derivatives. Such resistance determinants most probably were acquired by pathogenic bacteria from a pool of resistance genes in other microbial genera, including antibiotic-producing organisms. The resistance gene sequences were subsequently integrated by site-specific recombination into several classes of naturally occurring gene expression cassettes (typically "integrons") and disseminated within the microbial population by a variety of gene transfer mechanisms. Although bacterial conjugation once was believed to be restricted in host range, it now appears that this mechanism of transfer permits genetic exchange between many different bacterial genera in nature.19948153624