Tn <i>3</i> -derived inverted-repeat miniature elements (TIMEs) that mobilize antibiotic resistance genes
Bibliographic record
Abstract
ABSTRACT Miniature inverted-repeat transposable elements (MITEs) are nonautonomous mobile genetic elements (MGEs) that can be mobilized by transposases provided by the relevant autonomous MGEs. MITEs originating from Tn 3 -family transposons were previously termed Tn 3 -derived inverted-repeat miniature elements (TIMEs). Composite transposon-like structures bounded by two copies of TIME, called TIME-COMPs, were shown to mobilize the intervening sequences. However, their association with antibiotic resistance genes (ARGs) has not yet been systematically studied. This study thus aimed to identify new TIME-COMP-like structures containing ARGs in the genomic sequences of the clinically important bacterial family Enterobacteriaceae in public databases. TIME-COMP-like structures were first searched for in the plasmid database PLSDB, focusing on small plasmids, using a self-against-self blastn approach to identify repeated elements. Then, newly and previously identified MITEs (including TIMEs) were searched for in the NCBI core nucleotide database to identify TIME-COMP-like structures located on other replicons. Bioinformatic analysis identified multiple previously unreported TIME-COMPs containing ARGs, which are bounded by directly or inversely oriented TIMEs, namely, IS 101 , MITESen1, and a novel 244-bp TIME termed TIME244. TIME244 contains a putative resolution site related to that of Tn 21 . These TIMEs were predominantly detected in plasmids and very rarely in chromosomes. The ARGs embedded in newly identified TIME-COMPs were bla KPC-2 , floR , qnrS1 , and tet (A). Notably, the bla KPC-2 carbapenemase gene was found in TIME-COMPs bounded by TIME244 and a TIME-COMP bounded by IS 101 . These findings highlight a potential role for TIMEs in the spread of diverse ARGs. IMPACT STATEMENT Bacterial miniature inverted-repeat transposable elements (MITEs) are a group of short (50 bp–500 bp) nonautonomous transposable elements that are thought to have originated from insertion sequences or transposons. Although MITEs can theoretically mobilize antibiotic resistance genes (ARGs) in the presence of transposases, only a few studies have reported their association with ARGs, probably due to difficulties in identifying MITEs in genomic sequences. This study provides evidence, based on bioinformatic analysis of public Enterobacteriaceae genomes, that a subset of MITEs, called Tn 3 -derived inverted-repeat miniature elements (TIMEs), mobilizes ARGs by forming composite transposon-like structures. A novel 244-bp TIME, designated TIME244, was present in more than 100 Enterobacteriaceae plasmids in the current RefSeq database, suggesting its further transmission in bacterial populations through horizontal gene transfer. This study reveals that TIMEs were often overlooked when analyzing the genetic contexts of ARGs in previous studies. These findings highlight the importance of TIMEs in bacterial gene acquisition and underscore the need for new tools that can detect TIMEs in bacterial genomes for ARG surveillance. DATA SUMMARY Accession numbers of sequence data analyzed in this study are provided within the article or in supplementary data files.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".