The Natural History of Integrons
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Integrons were first identified because of their central role in assembling and disseminating antibiotic resistance genes in commensal and pathogenic bacteria. However, these clinically relevant integrons represent only a small proportion of integron diversity. Integrons are now known to be ancient genetic elements that are hotspots for genomic diversity, helping to generate adaptive phenotypes. This perspective examines the diversity, functions, and activities of integrons within both natural and clinical environments. We show how the fundamental properties of integrons exquisitely pre-adapted them to respond to the selection pressures imposed by the human use of antimicrobial compounds. We then follow the extraordinary increase in abundance of one class of integrons (class 1) that has resulted from its acquisition by multiple mobile genetic elements, and subsequent colonisation of diverse bacterial species, and a wide range of animal hosts. Consequently, this class of integrons has become a significant pollutant in its own right, to the extent that it can now be detected in most ecosystems. As human activities continue to drive environmental instability, integrons will likely continue to play key roles in bacterial adaptation in both natural and clinical settings. Understanding the ecological and evolutionary dynamics of integrons can help us predict and shape these outcomes that have direct relevance to human and ecosystem health.Bacteria mobile genetic elements consist of phage, plasmid, transposon, inserted sequences, integron, and genetic island, etc.Among them, conjugative plasmid, transposon, integron and genetic island etc are related to antibiotic resistance, and can be transferred between homogeneous and even heterogeneous bacteria, which promotes the progress of clinic drug resistance and multi-drug resistance.This paper reviews the progress in the studies of bacteria mobile genetic elements related to antibiotic resistance, including the category, characteristic, and transfer mechanism.
Horizontal Gene Transfer
Microbial genetics
DNA Transposable Elements
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Class 1 integrons and their impact on the mobility of antibiotic resistance in clinical environments
thesis submitted in fulfillment of the requirements of the degree of Master of Philosophy%%%%December 2013%%%%%%%%Bibliography:pages 98-115.%%%%Antibiotic resistance in pathogenic bacteria is becoming an increasingly important issue in the management of infectious diseases. Mortalities resulting from the inability to treat infections caused by resistant organisms have been recorded in significant numbers around the world. Mobile genetic elements such as integrons, transposons and gene cassettes, along with the lateral gene transfer which occurs between them, are largely responsible for the spread of resistance genes amongst pathogenic Gram negative bacteria. Integrons are gene expression systems capable of capturing and disseminating mobile gene elements such as gene cassettes. These gene cassettes, when associated with clinical integrons, predominantly code for antibiotic resistance genes. The fact that integrons allow both the integration and excision of multiple gene cassettes leads to the efficient spread of multi-drug resistance amongst pathogenic bacteria. This project investigates antibiotic resistance in Escherichia coli by examining class 1 integrons within several contexts. A collection of 718 E. coli isolates were obtained from clinical sources, primarily originating from urinary tract infections. These isolates were typed for antibiotic resistance capabilities and tested for class 1 and 2 integron presence. Integron cassette arrays were characterized, sequenced and mapped. In the collection, 23% of isolates carried class 1 integrons, while 3% carried a class 2 integron. Eight distinct cassette arrays were detected, consisting of gene cassettes solely from the aadA and dfrA families. Since identical integrons and cassette arrays appeared in a range of E. coli phylotypes and clonal lines, there appears to be significant and ongoing lateral gene transfer between E. coli lineages.%%%%%%%%1 online resource (152 pages) illustrations (some coloured), graphs, charts
Gene cassette
Horizontal Gene Transfer
Pathogenicity island
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Over the past 75 years, human pathogens have acquired antibiotic resistance genes (ARGs), often from environmental bacteria. Integrons play a major role in the acquisition of antibiotic resistance genes. We therefore hypothesized that focused exploration of integron gene cassettes from microbial communities could be an efficient way to find novel mobile resistance genes. DNA from polluted Indian river sediments were amplified using three sets of primers targeting class 1 integrons and sequenced by long- and short-read technologies to maintain both accuracy and context.Up to 89% of identified open reading frames encode known resistance genes, or variations thereof (> 1000). We identified putative novel ARGs to aminoglycosides, beta-lactams, trimethoprim, rifampicin, and chloramphenicol, including several novel OXA variants, providing reduced susceptibility to carbapenems. One dihydropteroate synthase gene, with less than 34% amino acid identity to the three known mobile sulfonamide resistance genes (sul1-3), provided complete resistance when expressed in Escherichia coli. The mobilized gene, here named sul4, is the first mobile sulfonamide resistance gene discovered since 2003. Analyses of adjacent DNA suggest that sul4 has been decontextualized from a set of chromosomal genes involved in folate synthesis in its original host, likely within the phylum Chloroflexi. The presence of an insertion sequence common region element could provide mobility to the entire integron. Screening of 6489 metagenomic datasets revealed that sul4 is already widespread in seven countries across Asia and Europe.Our findings show that exploring integrons from environmental communities with a history of antibiotic exposure can provide an efficient way to find novel, mobile resistance genes. The mobilization of a fourth sulfonamide resistance gene is likely to provide expanded opportunities for sulfonamide resistance to spread, with potential impacts on both human and animal health.
Gene cassette
Dihydropteroate synthase
Horizontal Gene Transfer
Genomic island
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A comparative genetic analysis of 42 clinical Klebsiella pneumoniae isolates, resistant to two or more antibiotics belonging to the broad-spectrum β-lactam group, sourced from Sydney, Australia, and three South American countries is presented. The study focuses on the genetic contexts of class 1 integrons, mobilizable genetic elements best known for their role in the rapid evolution of antibiotic resistance among Gram-negative pathogens. It was found that the class 1 integrons in this cohort were located in a number of different genetic contexts with clear regional differences. In Sydney, IS26-associated Tn21-like transposons on IncL/M plasmids contribute greatly to the dispersal of integron-associated multiple-drug-resistant (MDR) loci. In contrast, in the South American countries, Tn1696-like transposons on an IncA/C plasmid(s) appeared to be disseminating a characteristic MDR region. A range of mobile genetic elements is clearly being recruited by clinically important mobile class 1 integrons, and these elements appear to be becoming more common with time. This in turn is driving the evolution of complex and laterally mobile MDR units and may further complicate antibiotic therapy.
Klebsiella
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OBJECTIVE To investigate the distribution of drug efflux genes and mobile genetic elements in Pseudomonas aeruginosa(PAE)isolated from clinic.METHODS A total of 40 strains of P.aeruginosa were collected,20 from Guiyang area in Guizhou province assigned as group A and another 20 from Sunan area in Jiangsu province as group B.The antimicrobial susceptibility test(AST) was performed for 19 antibiotics with K-B method,and the drug efflux pump genes(smr,smr-2,qacE△1) and mobile genetic elements including genetic markers of the plasmid(traF,trbC),insert sequence(IS1133,ISEcp1),transposon(merA,tnpU,tnp513) and integron(qacE△,the first kind of integron genetic markers) were amplified by PCR,then the positive genes were sequenced and the sequencing results were analyzed by Blast.RESULTS PAEs in both two groups were multidrug-resistant to β-lactamases,aminoglycoside and fluoroquinolones;qacE△1 and merA were detected in group A with the positive rates of 10.0% and 5.0%,respectively;qacE△1,merA,tnpU and tnp513 genes were detected in group B with the positive rates of 100.0%,85.0%,5.0% and 55.0%,respectively.CONCLUSION The multidrug-resistant phenotype of PAE is associated with drug efflux genes and mobile genetic elements.
Efflux
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OBJECTIVE To investigate the distribution of genetic markers of mobile genetic elements: transposons,insertion sequences and integron in multidrug-resistant Acinetobacter baumannii.METHODS From Jan to Dec 2008,20 strains of multidrug-resistant A.baumannii isolated from sputum were collected from a hospital of a county-level city.Then,5 kinds of genetic markers of mobile genetic elements(tnpU,tnp513,IS26,ISaba1,intⅠ1) were analyzed by PCR.RESULTS All 5 kinds of genetic markers of mobile genetic elements were detected,and 15 strains(75.0%),15 strains(75.0%),18 strains(90.0%),17 strains(85.0%),15 strains(75.0%)were detected to carry tnpU,tnp513,IS26,ISaba1,intⅠ1,respectively.CONCLUSION The high rate of drug resitance of MDR-ABA to beta-lactams,aminoglycosides,quinolones is associated to 5 kinds of genetic markers of mobile genetic elements detected in 20 strains of multidrug-resistant A.baumannii.
Acinetobacter baumannii
Insertion sequence
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Gene cassette
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Integron,a mobile DNA element that can capture and carry genes based upon which integrase gene they contain,particularly those responsible for antibiotic resistance.It is the simplest mobile DNA element ever know and contains two parts which are gene cassettes and a recombined site called 59-base element.It has been divided two class,Resistant Integron and Super Integron,based on integrase genes it contained and the difference of gene cassette’s function it captured.Gene cassettes are the mobile element which can be integrated into or cutted out from integron by the integrases.Gene cassettes always have two functional parts including a gene which inhabited the most sequences and a recombined site downstream the gene.Most of gene cassettes are antibiotics-resistant gene,and others are the function-unknown ORF.Integron and gene cassettes are possibly important in the capture of antibiotics-resistant and evolution of bacteria genome.
Integrases
Gene cassette
Horizontal Gene Transfer
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Integrases
Gene cassette
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Horizontal Gene Transfer
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