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Costly Class-1 integrons and the domestication of the the functional integrase.

ABSTRACT: Class-1 integrons play an important role in the emergence and spread of antimicrobial resistance determinants. In a recent study we showed that host fitness was dramatically reduced following acquisition of these elements. These fitness costs were due to the presence of an active integrase and we suggested that the mechanistic explanation was due to reduced genetic stability through IntI1 mediated recombination events between attI/attC and non-canonical sites in the chromosome. Here we demonstrate that the attI degenerated target sequence is highly prevalent in our model organism Acinetobacter baylyi adding support to the hypothesis that IntI1 is costly due to genomic instability.

SUBMITTER: Harms K

PROVIDER: S-EPMC3681742 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Costly Class-1 integrons and the domestication of the the functional integrase.

Harms Klaus K Starikova Irina I Johnsen Pål J PJ

Mobile genetic elements 20130301 2

Class-1 integrons play an important role in the emergence and spread of antimicrobial resistance determinants. In a recent study we showed that host fitness was dramatically reduced following acquisition of these elements. These fitness costs were due to the presence of an active integrase and we suggested that the mechanistic explanation was due to reduced genetic stability through IntI1 mediated recombination events between <i>attI</i>/<i>attC</i> and non-canonical sites in the chromosome. Her ...[more]

PMID: 23914313

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Project description:BACKGROUND: Class 1 integrons are one of the most successful elements in the acquisition, expression and spread of antimicrobial resistance genes (ARG) among clinical isolates. Little is known about the gene flow of the components of the genetic platforms of class 1 integrons within and between bacterial communities. Thus it is important to better understand the interactions among "environmental" intI1, its genetic platforms and its distribution with human activities. METHODOLOGY/PRINCIPAL FINDINGS: An evaluation of two types of genetic determinants, ARG (sul1 and qacE1/qacE?1 genes) and lateral genetic elements (LGE) (intI1, ISCR1 and tniC genes) in a model of a culture-based method without antibiotic selection was conducted in a gradient of anthropogenic disturbances in a Patagonian island recognized as being one of the last regions containing wild areas. The intI1, ISCR1 genes and intI1 pseudogenes that were found widespread throughout natural communities were not associated with urbanization (p>0.05). Each ARG that is embedded in the most common genetic platform of clinical class 1 integrons, showed different ecological and molecular behaviours in environmental samples. While the sul1 gene frequency was associated with urbanization, the qacE1/qacE?1 gene showed an adaptive role to several habitats. CONCLUSIONS/SIGNIFICANCE: The high frequency of intI1 pseudogenes suggests that, although intI1 has a deleterious impact within several genomes, it can easily be disseminated among natural bacterial communities. The widespread occurrence of ISCR1 and intI1 throughout Patagonian sites with different degree of urbanization, and within different taxa, could be one of the causes of the increasing frequency of multidrug-resistant isolates that have characterized Argentina for decades. The flow of ARG and LGE between natural and clinical communities cannot be explained with a single general process but is a direct consequence of the interaction of multiple factors operating at molecular, ecological, phylogenetic and historical levels.

Project description:Class 1 integrons are widespread genetic elements that allow bacteria to capture and express gene cassettes that are usually promoterless. These integrons play a major role in the dissemination of antibiotic resistance among Gram-negative bacteria. They typically consist of a gene (intI) encoding an integrase (that catalyzes the gene cassette movement by site-specific recombination), a recombination site (attI1), and a promoter (Pc) responsible for the expression of inserted gene cassettes. The Pc promoter can occasionally be combined with a second promoter designated P2, and several Pc variants with different strengths have been described, although their relative distribution is not known. The Pc promoter in class 1 integrons is located within the intI1 coding sequence. The Pc polymorphism affects the amino acid sequence of IntI1 and the effect of this feature on the integrase recombination activity has not previously been investigated. We therefore conducted an extensive in silico study of class 1 integron sequences in order to assess the distribution of Pc variants. We also measured these promoters' strength by means of transcriptional reporter gene fusion experiments and estimated the excision and integration activities of the different IntI1 variants. We found that there are currently 13 Pc variants, leading to 10 IntI1 variants, that have a highly uneven distribution. There are five main Pc-P2 combinations, corresponding to five promoter strengths, and three main integrases displaying similar integration activity but very different excision efficiency. Promoter strength correlates with integrase excision activity: the weaker the promoter, the stronger the integrase. The tight relationship between the aptitude of class 1 integrons to recombine cassettes and express gene cassettes may be a key to understanding the short-term evolution of integrons. Dissemination of integron-driven drug resistance is therefore more complex than previously thought.

Dataset Information

Costly Class-1 integrons and the domestication of the the functional integrase.

Publications

Costly Class-1 integrons and the domestication of the the functional integrase.

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