RASTA-Bacteria: a web-based tool for identifying toxin-antitoxin loci in prokaryotes.
Ontology highlight
ABSTRACT:
SUBMITTER: Sevin EW
PROVIDER: S-EPMC2374986 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Prokaryotic chromosomes code for toxin-antitoxin (TA) loci, often in multiple copies. In E.coli, experimental evidence indicates that TA loci are stress-response elements that help cells survive unfavorable growth conditions. The first gene in a TA operon codes for an antitoxin that combines with and neutralizes a regulatory 'toxin', encoded by the second gene. RelE and MazF toxins are regulators of translation that cleave mRNA and function, in interplay with tmRNA, in quality control of gene expression. Here, we present the results from an exhaustive search for TA loci in 126 completely sequenced prokaryotic genomes (16 archaea and 110 bacteria). We identified 671 TA loci belonging to the seven known TA gene families. Surprisingly, obligate intracellular organisms were devoid of TA loci, whereas free-living slowly growing prokaryotes had particularly many (38 in Mycobacterium tuberculosis and 43 in Nitrosomonas europaea). In many cases, TA loci were clustered and closely linked to mobile genetic elements. In the most extreme of these cases, all 13 TA loci of Vibrio cholerae were bona fide integron elements located in the V.cholerae mega-integron. These observations strongly suggest that TA loci are mobile cassettes that move frequently within and between chromosomes and also lend support to the hypothesis that TA loci function as stress-response elements beneficial to free-living prokaryotes.
| S-EPMC549392 | biostudies-literature
Project description:Humans vary considerably both in their baseline and activated immune phenotypes. We developed a user-friendly open-access web portal, ImmuneRegulation, that enables users to interactively explore immune regulatory elements that drive cell-type or cohort-specific gene expression levels. ImmuneRegulation currently provides the largest centrally integrated resource on human transcriptome regulation across whole blood and blood cell types, including (i) ?43,000 genotyped individuals with associated gene expression data from ?51,000 experiments, yielding genetic variant-gene expression associations on ?220 million eQTLs; (ii) 14 million transcription factor (TF)-binding region hits extracted from 1945 ChIP-seq studies; and (iii) the latest GWAS catalog with 67,230 published variant-trait associations. Users can interactively explore associations between queried gene(s) and their regulators (cis-eQTLs, trans-eQTLs or TFs) across multiple cohorts and studies. These regulators may explain genotype-dependent gene expression variations and be critical in selecting the ideal cohorts or cell types for follow-up studies or in developing predictive models. Overall, ImmuneRegulation significantly lowers the barriers between complex immune regulation data and researchers who want rapid, intuitive and high-quality access to the effects of regulatory elements on gene expression in multiple studies to empower investigators in translating these rich data into biological insights and clinical applications, and is freely available at https://immuneregulation.mssm.edu.
| S-EPMC6602512 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-06-11 | GSE144030 | GEO
Project description:Toxin-antitoxin (TA) modules, composed of a toxic protein and a counteracting antitoxin, play important roles in bacterial physiology. We examined the experimental insertion of 1.5 million genes from 388 microbial genomes into an Escherichia coli host using more than 8.5 million random clones. This revealed hundreds of genes (toxins) that could only be cloned when the neighboring gene (antitoxin) was present on the same clone. Clustering of these genes revealed TA families widespread in bacterial genomes, some of which deviate from the classical characteristics previously described for such modules. Introduction of these genes into E. coli validated that the toxin toxicity is mitigated by the antitoxin. Infection experiments with T7 phage showed that two of the new modules can provide resistance against phage. Moreover, our experiments revealed an "antidefense" protein in phage T7 that neutralizes phage resistance. Our results expose active fronts in the arms race between bacteria and phage.
| S-EPMC3644417 | biostudies-literature
Project description:TADB2.0 (http://bioinfo-mml.sjtu.edu.cn/TADB2/) is an updated database that provides comprehensive information about bacterial type II toxin-antitoxin (TA) loci. Compared with the previous version, the database refined and the new data schema is employed. With the aid of text mining and manual curation, it recorded 6193 type II TA loci in 870 replicons of bacteria and archaea, including 105 experimentally validated TA loci. In addition, the newly developed tool TAfinder combines the homolog searches and the operon structure detection, allowing the prediction for type II TA pairs in bacterial genome sequences. It also helps to investigate the genomic context of predicted TA loci for putative virulence factors, antimicrobial resistance determinants and mobile genetic elements via alignments to the specific public databases. Additionally, the module TAfinder-Compare allows comparing the presence of the given TA loci across the close relative genomes. With the recent updates, TADB2.0 might provide better support for understanding the important roles of type II TA systems in the prokaryotic life activities.
| S-EPMC5753263 | biostudies-literature
Project description:CRISPR/Cas systems have gained prominence as powerful tools for genome engineering. Recent investigations into the crucial role of transposable elements (TEs) have stimulated research interest in manipulating TEs to elucidate their functions. Nevertheless, designing single guide RNAs (sgRNAs) that are both specific and efficient for TE manipulation presents a formidable challenge, considering the repetitive nature and high copy numbers of TEs. Although various sgRNA design tools have been developed for gene editing, an optimized sgRNA designer explicitly for TE manipulation has yet to be established. To bridge this gap, we presented CRISPR-TE, a web-based application featuring an accessible graphical user interface, available at https://www.crisprte.cn. CRISPR-TE could identify all potential sgRNAs for TEs and offers a comprehensive solution for efficient TE targeting at both the single duplicate and subfamily levels. We also demonstrated that young TEs can be targeted with higher coverage at the subfamily level. Finally, we validated the overexpression of SVAD, a human-specific TE, using dCas9-VP64 activator incorporated with three sgRNAs designed by our tool. Collectively, our findings suggest that CRISPR-TE may serve as a versatile framework for designing sgRNAs aimed at TE targeting.
2024-03-24 | GSE228266 | GEO
Project description:Long-term, recombinant gene expression in mammalian cells depends on the nature of the transgene integration site and its inherent properties to modulate transcription (epigenetic effects). Here we describe a method by which high transgene expression is achieved and stabilized in extensively proliferating cultures. The method is based on strict co-expression of the transgene with an antitoxin in cells that express the respective toxin. Since the strength of antitoxin expression correlates with an advantage for cell growth, the cells with strong antitoxin expression are enriched over time in cultures of heterogeneous cells. This principle was applied to CHO cell lines that conditionally express the toxin kid and that are transduced to co-express the antitoxin kis together with different transgenes of interest. Cultivation of pools of transfectants that express the toxin steadily increase their transgene expression within several weeks to reach a maximum that is up to 120-fold over the initial status. In contrast, average transgene expression drops in the absence of toxin expression. Together, we show that cells conditionally expressing kid can be employed to create overexpressing cells by a simple coupling of kis to the transgene of interest, without further manipulation and in absence of selectable drugs.
| S-EPMC2836568 | biostudies-literature
Project description:The human gastrointestinal microbiota (HGM) is known for its rich diversity of bacterial species and strains. Yet many studies stop at characterizing the HGM at the family level. This is mainly due to lack of adequate methods for a high-resolution profiling of the HGM. One way to characterize the strain diversity of the HGM is to look for strain-specific functional markers. Here, we propose using type II toxin-antitoxin systems (TAS). To identify TAS systems in the HGM, we previously developed the software TAGMA. This software was designed to detect the TAS systems, MazEF and RelBE, in lactobacilli and bifidobacteria. In this study, we updated the gene catalog created previously and used it to test our software anew on 1346 strains of bacteria, which belonged to 489 species and 49 genera. We also sequenced the genomes of 20 fecal samples and analyzed the results with TAGMA. Although some differences were detected at the strain level, the results showed no particular difference in the bacterial species between our method and other classic analysis software. These results support the use of the updated catalog of genes encoding type II TAS as a useful tool for computer-assisted species and strain characterization of the HGM.
| S-EPMC7354421 | biostudies-literature
Project description:Bacterial toxin-antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein-protein interactions. Accumulating knowledge about the structure-function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems.
| S-EPMC5086665 | biostudies-literature
Project description:The prokaryotic toxin-antitoxin systems (TAS, also referred to as TA loci) are widespread, mobile two-gene modules that can be viewed as selfish genetic elements because they evolved mechanisms to become addictive for replicons and cells in which they reside, but also possess "normal" cellular functions in various forms of stress response and management of prokaryotic population. Several distinct TAS of type 1, where the toxin is a protein and the antitoxin is an antisense RNA, and numerous, unrelated TAS of type 2, in which both the toxin and the antitoxin are proteins, have been experimentally characterized, and it is suspected that many more remain to be identified.We report a comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems in prokaryotes. Using sensitive methods for distant sequence similarity search, genome context analysis and a new approach for the identification of mobile two-component systems, we identified numerous, previously unnoticed protein families that are homologous to toxins and antitoxins of known type 2 TAS. In addition, we predict 12 new families of toxins and 13 families of antitoxins, and also, predict a TAS or TAS-like activity for several gene modules that were not previously suspected to function in that capacity. In particular, we present indications that the two-gene module that encodes a minimal nucleotidyl transferase and the accompanying HEPN protein, and is extremely abundant in many archaea and bacteria, especially, thermophiles might comprise a novel TAS. We present a survey of previously known and newly predicted TAS in 750 complete genomes of archaea and bacteria, quantitatively demonstrate the exceptional mobility of the TAS, and explore the network of toxin-antitoxin pairings that combines plasticity with selectivity.The defining properties of the TAS, namely, the typically small size of the toxin and antitoxin genes, fast evolution, and extensive horizontal mobility, make the task of comprehensive identification of these systems particularly challenging. However, these same properties can be exploited to develop context-based computational approaches which, combined with exhaustive analysis of subtle sequence similarities were employed in this work to substantially expand the current collection of TAS by predicting both previously unnoticed, derived versions of known toxins and antitoxins, and putative novel TAS-like systems. In a broader context, the TAS belong to the resistome domain of the prokaryotic mobilome which includes partially selfish, addictive gene cassettes involved in various aspects of stress response and organized under the same general principles as the TAS. The "selfish altruism", or "responsible selfishness", of TAS-like systems appears to be a defining feature of the resistome and an important characteristic of the entire prokaryotic pan-genome given that in the prokaryotic world the mobilome and the "stable" chromosomes form a dynamic continuum.This paper was reviewed by Kenn Gerdes (nominated by Arcady Mushegian), Daniel Haft, Arcady Mushegian, and Andrei Osterman. For full reviews, go to the Reviewers' Reports section.
| S-EPMC2701414 | biostudies-literature