The battle between humans and microbes has been waged since time immemorial. T h e em ergen ce an d sp read o f an tib io tic resistan ce am on g bacterial p ath ogen s is th e m ost strikin g exam p le o f evo lu tio n th at h as b een o b served in b acteria. Prevalence and characterization of integrons from bacteria. Gene cassette transcription in a large integronassociated. Reconstructing the history of class 1 integrons might help us control further spread of. Acquisition of genomic islands plays a central part in bacterial evolution as a mechanism of diversification and adaptation. Identification and analysis of integrons and cassette arrays in bacterial genomes. Past, present, and future microbiology and molecular. In this study, by using clone library analysis and highthroughput sequencing, we.
Chromosomally located integrons ci have been identified in a large number of environmental gramnegative bacteria. Although these genetic elements are potent agents of change, their contributions to the mode and tempo of bacterial evolution have just begun to be examined 4. Transferability of integrons, especially class 1 integrons, has been found to be common among bacteria through the horizontal gene transfer mechanism 14. Impact of wastewater treatment on the prevalence of integrons. Here, we provide a systematic analysis of the distribution and diversity of integron inti genes and integroncontaining.
They are ancient elements that are a hot spot for genomic complexity, generating phenotypic diversity and shaping adaptive responses. Integron diversity in heavymetalcontaminated mine tailings and inferences about integron evolution. Two environmental strains, delftia acidovorans c17 and delftia tsuruhatensis a90, were found to carry class 3 integrons, which have seldom been reported and then only from pathogens in which they are associated with antibiotic resistance genes. Antimicrobial agents have been used for the treatment of many bacterial. Molecular characterization of class 3 integrons from delftia. An analysis of the evolutionary relationships of integron. Oct 01, 2001 as such, integrondriven gene capture is likely to be an important factor in the more general process of horizontal gene transfer in the evolution of bacterial genomes.
The integron platform allows the acquisition, expression, and dissemination of antibiotic resistance genes within gene cassettes. Class 1 integrons are lowcost structures in escherichia coli nature. Apr 15, 2011 while integrons mobilize ar gene cassettes, they themselves are not mobile. Frontiers global evolution of pathogenic bacteria with. The program also produces a figure in pdf format representing each complete.
Thus, understanding the dynamics of integron activity has the potential to inform us of new threats linked to rapid bacterial evolution and improve our screening and mitigation approaches. The presence of integrons was assessed in gut bacteria isolated from wildcaught prawns. Genomic islands are dynamic, ancient integrative elements in. Multiple and complex expression regulation mechanisms involving mobile genetic elements in integrons have been developed in the evolution of shigella strains. Wastewater treatment plants wwtps contain abundant resistance genes. Hgt, including the transmission of ar genes are of prime importance in bacterial evolution, 8,17,18, since bacterial genomes have a remarkable ability to take up and express new genes 19. Cassettes usually contain only one gene, potentially any gene, and an attc recombination site, and thousands of cassettes have been sequenced. Bacteria from fildes peninsula carry class 1 integrons and antibiotic. Bacteria from fildes peninsula carry class 1 integrons and antibiotic resistance genes in conjugative plasmids. Resistance patterns and integron cassette arrays of. In turn, this implies that a single event resulted in the movement of one variant of the class 1 integron into the human microbiota. These are important in the exchange of antibiotic resistance determinants, but can also transfer a diverse suite of genes unrelated to pathogenicity. Describe the features of the f factor that allow it to 1. Integron cassettes are incorporated to the atti site of the integron platform by sitespecific.
The gain and loss of chromosomal integron systems in the. Identification and analysis of integrons and cassette arrays. Genetic diversity analyses of class 1 integrons and their. Identify the types of plasmids that are important creators of genetic variation 2. The evolution of class 1 integrons and the rise of. The association of multiple resistance integrons mris with mobile dna elements facilitates their transit across phylogenetic boundaries and augments the potential impact of integrons on bacterial evolution. To obtain current epidemiological data for integrons from enterobacteriae in hospital, the study characterizes the genetic structure in in1059 by comparison with in846 integrons harbouring vim gene and other class 1 integrons including in37, in62, in843 and in1021 with the aim of identifying. Distribution of class 1 and 2 integrons among serovars. Integron systems are now recognized as important agents of bacterial evolution and are prevalent in most environments. Bennett bristol centre for antimicrobial research and evaluation bcare, university of bristol, department of pathology and microbiology, school of medical sciences, university walk, bristol bs8 1td, uk. Apr 25, 2002 bacterial resistance evolution was then assayed by monitoring integrase. Here, the basic biology of integrons and superintegrons, their. This encodes an integrase, a recombined site, and a promoter. The role of integrons and gene cassettes in the dissemination of multidrug resistance in gramnegative.
Here, we provide a systematic analysis of the distribution and diversity of integron inti genes and integron containing. Despite a trend of declining consumption, resistance to cotrimoxazole has increased during a 12year period in stockholm. One of the human pathogens known to harbor chromosomal integrons, the treponema spirochetes are the only clade among spirochete species found to carry integrons. The human intestinal microbiota plays a major beneficial role in immune development and resistance to pathogens. Integrons are genetic elements associated with resistance to antimicrobial agents. These dna elements contain hundreds of accessory genes and constitute a significant fraction of the genomes of many bacterial species.
They are able to capture gene cassettes from the environment and incorporate them using sitespecific recombination. Integrons are versatile gene acquisition systems commonly found in bacterial genomes. Mechanisms of genetic variation bellarmine university. Proteobacteria 38,70, and we found calin in firmicutes and in0 in actinobacteria. A pseudomonad was recovered that contained a tn 402 like class 1 integron with a complete transposition module and two gene cassettes. Metagenomic libraries identify the entire genetic complement of newly discovered life forms, without the need to culture the organisms. Their contribution to bacterial evolution is being revealed by bacterial genome sequencing 53, which shows that plasmids and phages are important instruments in the divergence of closely related.
Integrons are genetic units found in many bacterial species that are defined by their ability to capture small mobile elements called gene cassettes. Two bacterial groups were selected to represent aquatic naturally occurring bacteria aeromonas and bacteria mainly introduced due to human activity enterobacteriaceae. May 31, 2008 integrons are mechanisms that facilitate horizontal gene transfer, allowing bacteria to integrate and express foreign dna. Class 1 and class 2 integrons in multidrugresistant gramnegative bacteria isolated from the salmon river, british columbia hai xu, a klaas broersma, b vivian miao, c julian davies c a state key laboratory of microbial technology, shandong university, jinan 250100, shandong, peoples republic of china. Integrons are linked to mobile dna elements such as transposons and conjugative plasmids that enable horizontal spread through bacterial populations fluit and schmitz 2004. The evolution of class 1 integrons and the rise of antibiotic. Bacteria have existed from very early in the history of life on earth. The rapid appearance and rise of the class 1 integron is one of the most stunning examples of evolution in action, driven by the power of natural selection. Class 1 integrons have played a major role in spreading multidrugresistance in bacteria. Are humans increasing bacterial evolvability trends in. Use of chromosomal integron arrays as a phylogenetic typing system for vibrio cholerae pandemic strains. The molecular background to this surprising development was investigated by using pcr to screen for integrons and specific resistance genes, followed by sequence analysis of selected integrons, in 105 clinical urinary isolates of gramnegative bacteria selected partly for. For a brief period, following the discovery and development of the main groups of antibiotics, mankind appeared to gain the upper hand against the legion of bacteria responsible for much morbidity and mortality among humans and their domestic animals, but the advantage was illusory, because the bacteria were quietly.
A pseudomonad was recovered that contained a tn402like class 1 integron with a complete transposition module and two gene cassettes. Integron identification in bacterial genomes and cassette. Transferable integrons of gramnegative bacteria isolated. The elements that contribute to the genome plasticity are mobile genetic elements mge transposons, integrons, and conjugative transposons. It appears that multiresistant integrons have evolved from sis through entrapment of inti genes and their cognate atti sites into highly mobile structures like transposons. These cells and genes are disseminated simultaneously with the original selective agents via human waste streams. Integrons have a capability to excise gene cassettes which are not useful for the host bacterial cell, but these cassettes remain stable in many bacterial isolates. Preclinical class 1 integron with a complete tn402like. Insights and inferences about integron evolution from. The integron is a powerful system which, by capturing, stockpiling, and rearranging new functions carried by gene encoding cassettes, confers upon bacteria a rapid adaptation capability in changing environments. Integrons are genetic elements first described at the end of the 1980s.
These genes are embedded in a specific genetic structure called gene cassette that generally carries one promoterless open reading frame together with a recombination site. The emergence and spread of antibiotic resistance among bacterial pathogens is the most striking example of evolution that has. It is likely that a single environmental class 1 integron gave rise to the ancestor of clinical class 1 integrons, since these all share a highly conserved inti1 sequence 7. The elements that contribute to the genome plasticity are mobile genetic elements mge transposons, integrons. Bacteria fossils discovered in rocks date from at least the devonian period 419. Thus, the detection and characterization of these integrons in waterborne pathogens, especially in epidemic and pandemic strains, is of the utmost importance. The emergence and spread of antibiotic resistance among bacterial pathogens is the most striking exam ple of evolution that has been observed in bacteria. Sedentary chromosomal integrons scis can stockpile and rearrange a myriad of different functions encoded in gene cassettes.
One cassette was identical to a previously described cassette from a chromosomal class 3 integron in delftia tsuruhatensis. They were first identified by virtue of their important. Integrons are genetic elements that allow the mobilization and expression of smaller elements called gene cassettes, and are considered to be key elements in the evolution of antibiotic resistance among enteric bacteria. The term has since been used for integrons of various cassette array lengths or for integrons on bacterial chromosomes versus, for example, plasmids. Although in nature integrons appear to be abundant, the presence of class 1 integrons in escherichia coli has been reported to be much less frequent among isolates of non. They are categorized into more than six classes, based on the int i gene sequence. Integrons in the intestinal microbiota as reservoirs for. Sitespecific insertion of genes into integrons role of the 59base element and determination of the recombination crossover point. Hgt, including the transmission of ar genes are of prime importance in bacterial evolution, 8,17,18, since bacterial genomes have a remarkable ability to take up and express new genes. Here we aimed at describing methods for the detection of integrons in sequenced bacterial genomes as well as for the experimental characterization of the activity of their different components. Attempts to control bacterial pathogens have led to an increase in antibioticresistant cells and the genetic elements that confer resistance phenotypes. Coevolution of microorganisms with environmental antibiotic materials has intensified the evolution of resistance mechanisms, which are usually classified into three types including intrinsic, acquired and. Insights and inferences about integron evolution from genomic. Sitespecific deletion and rearrangement of integron insert genes catalyzed by the integron dna integrase.
Integrons and gene cassettes in clinical isolates of co. Integrons are mechanisms that facilitate horizontal gene transfer, allowing bacteria to integrate and express foreign dna. The evolution of multiple novel and complex gene cassettes in integrons further suggests the selection and horizontal transfer of args in multidrug resistant bacteria. Class 1 integrons appeared in a number of different locations, and on different plasmids and transposons, coincident with the widespread use of antibiotics 5, 29. Aug 14, 2011 integrons are gene capture and expression systems that are characterized by the presence of an integrase gene. Although most integrons were initially described in human clinical isolates, they have now been identified in many non. Class 1 integrons have played a major role in the global dissemination of antibiotic resistance. Characterization of the novel in1059 harbouring vim gene.
Integrons and antibiotic resistance genes in waterborne. However, the clinical class 1 integrons responsible for this dissemination are just one sequence type in a larger family of class 1 integrons that are broadly distributed in environmental bacteria, and which exhibit considerable sequence diversity 5, 11. As the integron system has the ability to create novel combinations of resistance genes, it could represent a dynamic force in the evolution of multidrug resistant bacteria. Here we describe a class 1 integron that represents an intermediate stage in the evolutionary history of clinical. Integrons are ancient structures that have been present in bacteria for millions of years, indicating that bacteria had the means of acquiring and disseminating antibiotic resistance long before humans developed antibiotics. Bacteria from fildes peninsula carry class 1 integrons and. They were first identified by virtue of their important role in the spread of antibioticresistance genes. Evolutionary genomics of conjugative elements and integrons. Integrons are assembly platforms dna elements that acquire open reading frames embedded in exogenous gene cassettes and convert them to functional genes by ensuring their correct expression. Following induction of inti1 gene expression, r388 was transferred to e. The occurrence of integrons carrying antimicrobial resistance gene cassettes in aquatic environments has been reported, most particularly in contaminated water that contains agents that exert selective pressure on the bacteria therein.
The use of antibiotics, however, can cause the spread of antibiotic resistance genes within the resident intestinal microbiota. Integron analysis is also useful to study bacterial evolution and gene transfer because these elements can pass from bacterium to bacterium during conjugation. They were originally identified as a mechanism used by gramnegative bacteria to collect antibiotic resistance genes and express multiple resistance phenotypes in synergy with transposons. Molecular characterization of class 3 integrons from. Insights and inferences about integron evolution from genomic data. Accordingly, integrons have occasionally been identified in firmicutes and. Integrons are a peculiar group of genetic elements consisting of an integrase gene and a nearby recombination site at which mobile gene cassettes can be directionally inserted or excised by a sitespecific recombination mechanism catalyzed by the integron integrase. Genomic islands are nonselfmobilizing integrative and excisive elements that encode diverse functional characteristics but all contain a recombination module comprised of an integrase, associated attachment sites and, in some cases, a recombination directionality. Research article open access the gain and loss of chromosomal. 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. Jan, 2020 integrons are almost certain to play a key role in spreading these clinically relevant traits. On the basis of integrase amino acid sequence similarity, integrons are divided into five classes.
The program also produces a figure in pdf format rep resenting each. Pathogens free fulltext integrons in the intestinal microbiota as. The article has been formatted by wikipedias pdf export tool. In recent times, they have had a major role in the acquisition, expression, and dissemination of antibiotic resistance genes. Pathogens free fulltext integrons in the intestinal. Reconstructing the history of class 1 integrons might help us control further spread of antibiotic resistance by understanding how human activities influence microbial evolution. Resistance integrons are bacterial genetic platforms that can capture and express. Bacterial resistance evolution by recruitment of super.
These include pathogens for man, other animals and plants, as well as nonpathogenic bacteria. In fact, the evolution of the compulsive resistance of bacteria to antibiotics is great. Only in the past few years has it been appreciated that gene exchange is a universal property of bacteria that has occurred throughout eons of microbial evolution. The prevalence of classes 1 and 2 integrons among aeromonas sp. Class 1 and class 2 integrons in multidrugresistant gram. Some unknown mechanism probably hinders the establishment of integrons in these lineages after transfer. This suggests that carriage of integron borne resistance gene cassettes does not impose a significant burden on the bacteria. Integrons are genetic mechanisms that allow bacteria to adapt and evolve rapidly through the stockpiling and expression of new genes. Integrons are almost certain to play a key role in spreading these clinically relevant traits. Integron evolutionary history suggests that these sedentary. The gene cassette metagenome is a basic resource for bacterial genome evolution. Identification and analysis of integrons and cassette arrays in. Identification and analysis of integrons and cassette.
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