IntegronFinder 2.0: identification and analysis of integrons across Bacteria, with a focus on antibiotic resistance in Klebsiella

Néron, Bertrand; Littner, Eloi; Amandine, Perrin; Haudiquet, Matthieu; Cury, Jean; Rocha, Eduardo P. C.

doi:10.1101/2022.02.28.482270

Cited by 36 publications

(21 citation statements)

References 55 publications

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“…Analyses were performed by analyzing the FASTA files for the individual replicon types described above using the latest AMRFinderPlus database V3.2.1 (available at 1 ) and IntegronFinder (Néron et al, 2022). The AMRFinderPlus database has sequences for 983 unique AMR genes (including 6,060 total variants), 30 DBR genes (including 55 total variants) and 82 HMR genes (including 182 total variants).…”

Section: Identification Of Resistance Genes and Integrons Using Galax...mentioning

confidence: 99%

In silico analyses of diversity and dissemination of antimicrobial resistance genes and mobile genetics elements, for plasmids of enteric pathogens

Algarni

Han²,

Gudeta³

et al. 2023

Front. Microbiol.

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IntroductionThe antimicrobial resistance (AMR) mobilome plays a key role in the dissemination of resistance genes encoded by mobile genetics elements (MGEs) including plasmids, transposons (Tns), and insertion sequences (ISs). These MGEs contribute to the dissemination of multidrug resistance (MDR) in enteric bacterial pathogens which have been considered as a global public health risk.MethodsTo further understand the diversity and distribution of AMR genes and MGEs across different plasmid types, we utilized multiple sequence-based computational approaches to evaluate AMR-associated plasmid genetics. A collection of 1,309 complete plasmid sequences from Gammaproteobacterial species, including 100 plasmids from each of the following 14 incompatibility (Inc) types: A/C, BO, FIA, FIB, FIC, FIIA, HI1, HI2, I1, K, M, N, P except W, where only 9 sequences were available, was extracted from the National Center for Biotechnology Information (NCBI) GenBank database using BLAST tools. The extracted FASTA files were analyzed using the AMRFinderPlus web-based tools to detect antimicrobial, disinfectant, biocide, and heavy metal resistance genes and ISFinder to identify IS/Tn MGEs within the plasmid sequences.Results and DiscussionIn silico prediction based on plasmid replicon types showed that the resistance genes were diverse among plasmids, yet multiple genes were widely distributed across the plasmids from enteric bacterial species. These findings provide insights into the diversity of resistance genes and that MGEs mediate potential transmission of these genes across multiple plasmid replicon types. This notion was supported by the observation that many IS/Tn MGEs and resistance genes known to be associated with them were common across multiple different plasmid types. Our results provide critical insights about how the diverse population of resistance genes that are carried by the different plasmid types can allow for the dissemination of AMR across enteric bacteria. The results also highlight the value of computational-based approaches and in silico analyses for the assessment of AMR and MGEs, which are important elements of molecular epidemiology and public health outcomes.

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Section: Identification Of Resistance Genes and Integrons Using Galax...mentioning

confidence: 99%

In silico analyses of diversity and dissemination of antimicrobial resistance genes and mobile genetics elements, for plasmids of enteric pathogens

Algarni

Han²,

Gudeta³

et al. 2023

Front. Microbiol.

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“…To study the enrichment of TA systems within SCI across bacterial genomes, we used the dataset and integron predictions of IntegronFinder 2.0 [4]. Briefly, this dataset consists of 21,105 complete genomes retrieved from NCBI RefSeq on 30 March 2021.…”

Section: Genomes Dataset and Sci/bigcalin Annotationmentioning

confidence: 99%

“…To assess if a correlation could exist between the number of TAs and the size of the SCI cassette arrays, we used IntegronFinder 2.0 [4] to detect all of the sedentary integrons in complete genomes of the RefSeq NCBI database. We identified 398 genomes with at least one SCI (defined as an integron comprising strictly more than 10 cassettes, as suggested in [4]) or one large CALIN (BigCALIN, defined as a SCI lacking a functional integrase). In each of these genomes, we screened TA systems with TASmania [40], a predictor with very low false negative rate.…”

Section: Toxin-antitoxin Landscape In Sedentary Chromosomal Integrons...mentioning

confidence: 99%

“…They were originally found to be the genetic systems responsible for the gathering of resistance determinants in some mobile elements [1]. Integrons may play broader roles in bacterial adaptation, especially the numerous, large and poorly understood sedentary integrons [2][3][4][5]. Hence, we distinguish two types of integrons: Mobile Integrons (MI) and Sedentary Chromosomal Integrons (SCI).…”

Section: Introductionmentioning

confidence: 99%

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Cassette recombination dynamics within chromosomal integrons are regulated by toxin–antitoxin systems

Richard

Darracq

Littner

et al. 2022

Preprint

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The integron is a bacterial recombination system that allows acquisition, stockpiling and expression of promoterless genes embedded in cassettes. Some integrons, like the one found in the second chromosome of Vibrio cholerae, can be particularly massive and contain hundreds of non-expressed cassettes. It is unclear how such genetic structures can be stabilized in bacterial genomes. Here, we reveal that the orientation of integrons toward replication within bacterial chromosomes is essential to their stability. Indeed, we show that upon inversion of the V. cholerae chromosomal integron, its plasticity is dramatically increased. This correlates with a strong growth defect which we show is mostly due to the excision of a particular type of cassettes bearing their own promoter and encoding toxin-antitoxin systems. This so called abortive excision of toxin-antitoxin systems can prevent the inversion of chromosomal integrons and the associated extensive loss of cassettes. Our analysis of the available sedentary chromosomal integrons in genome database show a robust correlation between the size of the cassette array and the number of toxin-antitoxin cassettes. This study thus provides a striking example of the relationship between genome organization, genome stability, and an emerging property of toxin-antitoxin systems.

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“…The copyright holder for this this version posted September 13, 2022. ; https://doi.org/10.1101/2022.09.11.507474 doi: bioRxiv preprint cassettes found in SCIs are involved in mobility, metabolism, biofilm formation, bacteriophage resistance or host surface polysaccharide modification (2,4,9). Here, we focused on the ability of bacteria to access new functions and to build a repertoire of cassettes pertinent for their lifestyle.…”

Section: Introductionmentioning

confidence: 99%

A new route for integron cassette dissemination among bacterial genomes

Loot

Millot

Richard

et al. 2022

Preprint

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Integrons are genetic elements found exclusively in bacteria. They are well known for their role in disseminating antibiotic resistance genes among pathogens and more generally for enabling bacteria to rapidly adapt to changing environmental conditions. Integrons constitute a natural system to capture, stockpile, shuffle, express and disseminate genes embedded in cassettes. All these events are governed by the integron integrase through site-specific recombination between integron att sites (attC and attI sites). Here, we demonstrate that integron integrase can efficiently catalyze the insertion of cassettes in bacterial genomes, outside the att sites carried by the integron system. Surprisingly, analysis of more than 500,000 independent clones revealed that the genome recombination sites differ greatly, in terms of sequence and structure, from both classical attC and attI recombination sites. We named these new sites attG. Notably, among these a few are driving integration at very high rates. We also showed that, once inserted in genomes, cassettes can be expressed if located near a bacterial promoter. Moreover, even if occurring at low frequency, genome inserted cassettes can be excised precisely or imprecisely, inducing in this latter case, chromosomal modifications. These results unveil a new route for antibiotic resistance dissemination and expand the role of integrons in bacterial genome evolution.

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IntegronFinder 2.0: identification and analysis of integrons across Bacteria, with a focus on antibiotic resistance in Klebsiella

Cited by 36 publications

References 55 publications

In silico analyses of diversity and dissemination of antimicrobial resistance genes and mobile genetics elements, for plasmids of enteric pathogens

In silico analyses of diversity and dissemination of antimicrobial resistance genes and mobile genetics elements, for plasmids of enteric pathogens

Cassette recombination dynamics within chromosomal integrons are regulated by toxin–antitoxin systems

A new route for integron cassette dissemination among bacterial genomes

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