Mobile DNAPub Date : 2025-05-09DOI: 10.1186/s13100-025-00358-9
Mirko Ronzio, Andrea Bernardini, Alberto Gallo, Roberto Mantovani, Diletta Dolfini
{"title":"Binding of NF-Y to transposable elements in mouse and human cells.","authors":"Mirko Ronzio, Andrea Bernardini, Alberto Gallo, Roberto Mantovani, Diletta Dolfini","doi":"10.1186/s13100-025-00358-9","DOIUrl":"https://doi.org/10.1186/s13100-025-00358-9","url":null,"abstract":"<p><strong>Background: </strong>Transposable Elements (TEs) represent a sizeable amount of mammalian genomes, providing regulatory sequences involved in shaping gene expression patterns. NF-Y is a Transcription factor -TF- trimer that binds to the CCAAT box, belonging to a selected group implicated in determining initiation of coding and noncoding RNAs.</p><p><strong>Results: </strong>We focus on NF-Y TE locations in 8 human and 8 mouse cells. Binding is exclusive for retroviral LTR12, MLT1 and MER in human and RLTR10 and IAPLTR in mouse cells. Cobinding and analysis of the DNA matrices signal enrichment of distinct TFs neighboring CCAAT in the three TE classes: MAFK/F/G in LTR12 and USF1/2 in MLT1 with precise alignment of sites, PKNOX1, MEIS2, PBX2/3 TALE TFs in MER57. The presence of \"epigenetic\" marks in human cells indicate prevalent co-association with open chromatin in MER, closed in LTR12 and mixed in MLT1. Based on chromatin features, these locations are mostly marked as enhancers, as confirmed by analysis of loci predicted to generate eRNAs.</p><p><strong>Conclusions: </strong>These results are discussed in the context of functional data, suggesting a complex -positive and potentially-negative role of NF-Y on distinct classes of repetitive sequences.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"22"},"PeriodicalIF":4.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-05-07DOI: 10.1186/s13100-025-00359-8
Eleni Kyriakou, Gkikas Magiorkinis
{"title":"Compilation of all known HERV-K HML-2 proviral integrations.","authors":"Eleni Kyriakou, Gkikas Magiorkinis","doi":"10.1186/s13100-025-00359-8","DOIUrl":"https://doi.org/10.1186/s13100-025-00359-8","url":null,"abstract":"<p><p>Human endogenous retroviruses (HERVs) occupy 8% of the human genome. Although most HERV integrations are severely degenerated by mutations, the most recently integrated proviruses, such as members of the HERV-K HML-2 subfamily, partially retain regulatory and protein-coding capacity. The precise number of HML-2 proviral copies in the modern human population is constantly changing in literature, as new integrations are being uncovered. The first comprehensive list of HML-2 proviral loci was compiled in 2011, including a total of 91 proviruses. Since then, multiple articles published additions and modifications to that list, mainly in the form of new polymorphic proviral sites, updated chromosomal band characterizations or the correspondence of coordinates in the new version of the published human reference genome. In the present study, we systematically searched the literature for lists of HML-2 proviruses and their coordinates and cross-examined every proviral locus information, also against the human genome. We gathered all available data about all HML-2 proviral integrations identified to date and updated, corrected and refined the coordinates in both human genome assemblies currently used in research, to incorporate the whole provirus in each case. Thereby we present an exhaustive (to date) catalogue of all known HML-2 proviruses and their respective coordinates, as a powerful tool for studies aiming to decipher HERV role in health and disease, especially for high-throughput data analyses, which could lead to the discovery of links between specific HERV integrations and biological mechanisms or medical disorders.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"21"},"PeriodicalIF":4.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-04-22DOI: 10.1186/s13100-025-00357-w
Päivi Nummi, Tatiana Cajuso, Tuukka Norri, Aurora Taira, Heli Kuisma, Niko Välimäki, Anna Lepistö, Laura Renkonen-Sinisalo, Selja Koskensalo, Toni T Seppälä, Ari Ristimäki, Kyösti Tahkola, Anne Mattila, Jan Böhm, Jukka-Pekka Mecklin, Emma Siili, Annukka Pasanen, Oskari Heikinheimo, Ralf Bützow, Auli Karhu, Kathleen H Burns, Kimmo Palin, Lauri A Aaltonen
{"title":"Structural features of somatic and germline retrotransposition events in humans.","authors":"Päivi Nummi, Tatiana Cajuso, Tuukka Norri, Aurora Taira, Heli Kuisma, Niko Välimäki, Anna Lepistö, Laura Renkonen-Sinisalo, Selja Koskensalo, Toni T Seppälä, Ari Ristimäki, Kyösti Tahkola, Anne Mattila, Jan Böhm, Jukka-Pekka Mecklin, Emma Siili, Annukka Pasanen, Oskari Heikinheimo, Ralf Bützow, Auli Karhu, Kathleen H Burns, Kimmo Palin, Lauri A Aaltonen","doi":"10.1186/s13100-025-00357-w","DOIUrl":"https://doi.org/10.1186/s13100-025-00357-w","url":null,"abstract":"<p><strong>Background: </strong>Transposons are DNA sequences able to move or copy themselves to other genomic locations leading to insertional mutagenesis. Although transposon-derived sequences account for half of the human genome, most elements are no longer transposition competent. Moreover, transposons are normally repressed through epigenetic silencing in healthy adult tissues but become derepressed in several human cancers, with high activity detected in colorectal cancer. Their impact on non-malignant and malignant tissue as well as the differences between somatic and germline retrotransposition remain poorly understood. With new sequencing technologies, including long read sequencing, we can access intricacies of retrotransposition, such as insertion sequence details and nested repeats, that have been previously challenging to characterize.</p><p><strong>Results: </strong>In this study, we investigate somatic and germline retrotransposition by analyzing long read sequencing from 56 colorectal cancers and 112 uterine leiomyomas. We identified 1495 somatic insertions in colorectal samples, while striking lack of insertions was detected in uterine leiomyomas. Our findings highlight differences between somatic and germline events, such as transposon type distribution, insertion length, and target site preference. Leveraging long-read sequencing, we provide an in-depth analysis of the twin-priming phenomenon, detecting it across transposable element types that remain active in humans, including Alus. Additionally, we detect an abundance of germline transposons in repetitive DNA, along with a relationship between replication timing and insertion target site.</p><p><strong>Conclusions: </strong>Our study reveals a stark contrast in somatic transposon activity between colorectal cancers and uterine leiomyomas, and highlights differences between somatic and germline transposition. This suggests potentially different conditions in malignant and non-malignant tissues, as well as in germline and somatic tissues, which could be involved in the transposition process. Long-read sequencing provided important insights into transposon behavior, allowing detailed examination of structural features such as twin priming and nested elements.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"20"},"PeriodicalIF":4.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-04-16DOI: 10.1186/s13100-025-00356-x
Zhen Li, Nicolas Pollet
{"title":"Impact of a horizontally transferred Helitron family on genome evolution in Xenopus laevis.","authors":"Zhen Li, Nicolas Pollet","doi":"10.1186/s13100-025-00356-x","DOIUrl":"https://doi.org/10.1186/s13100-025-00356-x","url":null,"abstract":"<p><strong>Background: </strong>Within eukaryotes, most horizontal transfer of genetic material involves mobile DNA sequences and such events are called horizontal transposable element transfer (HTT). Although thousands of HTT examples have been reported, the transfer mechanisms and their impacts on host genomes remain elusive.</p><p><strong>Results: </strong>In this work, we carefully annotated three Helitron families within several Xenopus frog genomes. One of the Helitron family, Heli1Xen1, is recurrently involved in capturing and shuffling Xenopus laevis genes required in early embryonic development. Remarkably, we found that Heli1Xen1 is seemingly expressed in X. laevis and has produced multiple genomic polymorphisms within the X. laevis population. To identify the origin of Heli1Xen1, we searched its consensus sequence against available genome assemblies. We found highly similar copies in the genomes of another 13 vertebrate species from divergent vertebrate lineages, including reptiles, ray-finned fishes and amphibians. Further phylogenetic analysis provides evidence showing that Heli1Xen1 invaded these lineages via HTT quite recently, around 0.58-10.74 million years ago.</p><p><strong>Conclusions: </strong>The frequently Heli1Xen1-involved HTT events among reptiles, fishes and amphibians could provide insights into possible vectors for transfer, such as shared viruses across lineages. Furthermore, we propose that the Heli1Xen1 sequence could be an ideal candidate for studying the mechanism and genomic impact of Helitron transposition.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"19"},"PeriodicalIF":4.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-04-11DOI: 10.1186/s13100-025-00352-1
Matthew J Borok, Louai Zaidan, Frederic Relaix
{"title":"Transposon expression and repression in skeletal muscle.","authors":"Matthew J Borok, Louai Zaidan, Frederic Relaix","doi":"10.1186/s13100-025-00352-1","DOIUrl":"https://doi.org/10.1186/s13100-025-00352-1","url":null,"abstract":"<p><p>Transposons and their derivatives make up a major proportion of the human genome, but they are not just relics of ancient genomes. They can still be expressed, potentially affecting the transcription of adjacent genes, and can sometimes even contribute to their coding sequence. Active transposons can integrate into new sites in the genome, potentially modifying the expression of nearby loci and leading to genetic disorders. In this review, we highlight work exploring the expression of transposons in skeletal muscles and transcriptional regulation by the KRAB-ZFP/KAP1/SETDB1 complex. We next focus on specific cases of transposon insertion causing phenotypic variation and distinct muscular dystrophies, as well as the implication of transposon expression in immune myopathies. Finally, we discuss the dysregulation of transposons in facioscapulohumeral dystrophy and aging.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"18"},"PeriodicalIF":4.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-04-09DOI: 10.1186/s13100-025-00350-3
Edith Tittarelli, Elisa Carotti, Federica Carducci, Marco Barucca, Adriana Canapa, Maria Assunta Biscotti
{"title":"Transposable element dynamics in Xenopus laevis embryogenesis: a tale of two coexisting subgenomes.","authors":"Edith Tittarelli, Elisa Carotti, Federica Carducci, Marco Barucca, Adriana Canapa, Maria Assunta Biscotti","doi":"10.1186/s13100-025-00350-3","DOIUrl":"10.1186/s13100-025-00350-3","url":null,"abstract":"<p><p>The African clawed frog Xenopus laevis has an allotetraploid genome consisting of two subgenomes referred as L relating to the Long chromosomes and S relating to the Short chromosomes. While the L subgenome presents conserved synteny with X. tropicalis chromosomes, the S subgenome has undergone rearrangements and deletions leading to differences in gene and transposable element (TE) content between the two subgenomes. The asymmetry in the evolution of the two subgenomes is also detectable in gene expression levels and TE mobility. TEs, also known as \"jumping genes\", are mobile genetic elements having a key role in genome evolution and gene regulation. However, due to their potential deleterious effects, TEs are controlled by host defense mechanisms such as the nucleosome remodeling and deacetylase (NuRD) complex and the Argonaute proteins that mainly modify the heterochromatin environment. In embryogenesis, TEs can escape the silencing mechanisms during the maternal-to-zygotic transition when a transcriptionally permissive environment is created. Moreover, further evidence highlighted that the reactivation of TEs during early developmental stages is not the result of this genome-wide reorganization of chromatin but it is class and stage-specific, suggesting a precise regulation. In line with these premises, we explored the impact of TE transcriptional contribution in six developmental stages of X. laevis. Overall, the expression pattern referred to the entire set of transcribed TEs was constant across the six developmental stages and in line with their abundance in the genome. However, focusing on subgenome-specific TEs, our analyses revealed a distinctive transcriptional pattern dominated by LTR retroelements in the L subgenome and LINE retroelements in the S subgenome attributable to young copies. Interestingly, genes encoding proteins involved in maintaining the repressive chromatin environment were active in both subgenomes highlighting that TE controlling systems were active in X. laevis embryogenesis and evolved symmetrically.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"17"},"PeriodicalIF":4.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-04-03DOI: 10.1186/s13100-025-00353-0
Atsushi Takeda, Daisuke Nonaka, Yuta Imazu, Tsukasa Fukunaga, Michiaki Hamada
{"title":"REPrise: de novo interspersed repeat detection using inexact seeding.","authors":"Atsushi Takeda, Daisuke Nonaka, Yuta Imazu, Tsukasa Fukunaga, Michiaki Hamada","doi":"10.1186/s13100-025-00353-0","DOIUrl":"10.1186/s13100-025-00353-0","url":null,"abstract":"<p><strong>Background: </strong>Interspersed repeats occupy a large part of many eukaryotic genomes, and thus their accurate annotation is essential for various genome analyses. Database-free de novo repeat detection approaches are powerful for annotating genomes that lack well-curated repeat databases. However, existing tools do not yet have sufficient repeat detection performance.</p><p><strong>Results: </strong>In this study, we developed REPrise, a de novo interspersed repeat detection software program based on a seed-and-extension method. Although the algorithm of REPrise is similar to that of RepeatScout, which is currently the de facto standard tool, we incorporated three unique techniques into REPrise: inexact seeding, affine gap scoring and loose masking. Analyses of rice and simulation genome datasets showed that REPrise outperformed RepeatScout in terms of sensitivity, especially when the repeat sequences contained many mutations. Furthermore, when applied to the complete human genome dataset T2T-CHM13, REPrise demonstrated the potential to detect novel repeat sequence families.</p><p><strong>Conclusion: </strong>REPrise can detect interspersed repeats with high sensitivity even in long genomes. Our software enhances repeat annotation in diverse genomic studies, contributing to a deeper understanding of genomic structures.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"16"},"PeriodicalIF":4.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-04-02DOI: 10.1186/s13100-025-00354-z
Carlos M Vicient
{"title":"Retand LTR-retrotransposons in plants: a long way from pol to 3'LTR.","authors":"Carlos M Vicient","doi":"10.1186/s13100-025-00354-z","DOIUrl":"10.1186/s13100-025-00354-z","url":null,"abstract":"<p><strong>Background: </strong>Plant Gypsy LTR-retrotransposons are classified into lineages according to the phylogenetic relationships of the reverse transcriptase. Retand is a lineage of non-chromovirus elements characterized by the presence of a long internal region compared to other lineages.</p><p><strong>Results: </strong>This work focuses on the identification and characterization of Potentially Recently Active Retand Elements (PRAREs) in 617 genomic sequence assemblies of Viridiplantae species. The Retand elements were considered PRAREs if their LTRs and insertion sequences were identical, and the sizes of their internal regions and LTRs did not differ by more than 2% from the consensus. A total of 2,735 PRAREs were identified, distributed in 122 clusters corresponding to 34 species, with copy numbers per cluster varying between 1 and 180. They are present in Eudicotyledons and Liliopsida but not in other groups of plants. Some PRAREs are non-autonomous elements, lacking some of the typical LTR retrotransposon coding domains. The size of the POL-3'LTR regions varies between 2,933 and 6,566 bp, and in all cases, includes potential coding regions oriented antisense to the gag and pol genes. 97% of the clusters contain antisense ORFs encoding the TRP28 protein domain of unknown function. The analysis of the consensus TRP28 domain indicates that it probably can bind DNA. About half of the PRAREs contain arrays of tandem repeats in the POL-3'LTR region.</p><p><strong>Conclusions: </strong>The large internal region of the Retand elements is due to the presence of a long POL-3'LTR region. This region frequently contains arrays of tandem repeats that contribute to the expansion of this area. The presence of antisense ORFs in the POL-3'LTR region is also a common feature in these elements, many of which encode proteins with conserved domains, especially the TRP28 domain. The possible function of these TRP28-containing proteins is unknown, but their potential DNA binding capacity and the comparison with similar genes in some retroviruses suggest that they may play a regulatory role in the Retand transposition process.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"15"},"PeriodicalIF":4.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-03-25DOI: 10.1186/s13100-025-00355-y
Tetsuo Kon, Koto Kon-Nanjo, Oleg Simakov
{"title":"Subtelomeric repeat expansion in Hydractinia symbiolongicarpus chromosomes.","authors":"Tetsuo Kon, Koto Kon-Nanjo, Oleg Simakov","doi":"10.1186/s13100-025-00355-y","DOIUrl":"10.1186/s13100-025-00355-y","url":null,"abstract":"<p><p>Despite the striking conservation of animal chromosomes, their repetitive element complements are vastly diverse. Only recently, high quality chromosome-level genome assemblies enabled identification of repeat compositions along a broad range of animal chromosomes. Here, utilizing the chromosome-level genome assembly of Hydractinia symbiolongicarpus, a colonial hydrozoan cnidarian, we describe an accumulation of a single 372 bp repeat unit in the subtelomeric regions. Based on the sequence divergence, its partial affinity with the Helitron group can be detected. This sequence is associated with a repeated minisatellite unit of about 150 bp. Together, they account for 26.1% of the genome (126 Mb of the 483 Mb). This could explain the genome size increase observed in H. symbiolongicarpus compared with other cnidarians, yet distinguishes this expansion from other large cnidarian genomes, such as Hydra vulgaris, where such localized propagation is absent. Additionally, we identify a derivative of an IS3EU-like DNA element accumulated at the putative centromeric regions. Our analysis further reveals that Helitrons generally comprise a large proportion of H. symbiolongicarpus (11.8%). We investigated Helitron presence and distributions across several cnidarian genomes. We find that in Nematostella vectensis, an anthozoan cnidarian, Helitron-like sequences were similarly accumulated at the subtelomeric regions. All these findings suggest that Helitron derivatives are prone to forming chromosomal extensions in cnidarians through local amplification in subtelomeric regions, driving variable genome expansions within the clade.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"14"},"PeriodicalIF":4.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2025-03-24DOI: 10.1186/s13100-025-00351-2
Zhiyun Guo, Xia Qin, Maokui Yue, Lingling Wu, Ning Li, Jing Su, Meijie Jiang
{"title":"IS26 carrying bla<sub>KPC-2</sub> mediates carbapenem resistance heterogeneity in extensively drug-resistant Klebsiella pneumoniae isolated from clinical sites.","authors":"Zhiyun Guo, Xia Qin, Maokui Yue, Lingling Wu, Ning Li, Jing Su, Meijie Jiang","doi":"10.1186/s13100-025-00351-2","DOIUrl":"10.1186/s13100-025-00351-2","url":null,"abstract":"<p><strong>Background: </strong>Due to the widespread and irrational use of antibiotics, the emergence and prevalence of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) have become a major challenge in controlling bacterial infections in hospitals. The bla<sub>KPC-2</sub> gene located on mobile genetic elements has further complicated the control of resistant bacteria transmission.</p><p><strong>Results: </strong>In this study, K. pneumoniae strains were isolated from blood cultures of patients. Using the Kirby-Bauer disk diffusion method, we found carbapenem resistance heterogeneity. The resistant subpopulation KPTA-R1 and the sensitive subpopulation KPTA-S1 were purified. Whole-genome sequencing revealed that the bla<sub>KPC-2</sub> gene in KPTA-R1 was located on an IncFII plasmid (pKPC-R), within a composite transposon (PCTs) formed by two direct repeats of IS26 elements. The structure was identified as IS26-RecA-ISKpn27-bla<sub>KPC-2</sub>-ISKpn6-IS26. However, in KPTA-S1, a similar plasmid, pAR-S, lacked this segment. Sequence comparison analysis indicates that the deletion of this bla<sub>KPC-2</sub> encoding sequence in this IncFII plasmid is associated with transposition activity mediated by IS26. Multi-sequence comparison of the plasmids showed that the IS26 transposon facilitated the sequence polymorphism of these plasmids.</p><p><strong>Conclusion: </strong>This study reveals the key role of IS26-mediated transposition activity, through homologous recombination, in the emergence of carbapenem resistance heterogeneity in clinical K. pneumoniae strains carrying bla<sub>KPC-2</sub>. IS26 is able to promote the evolution of resistance in the IncFII plasmid, and through copy-in cointegration or targeted conservative cointegration may result in the acquisition or loss of antibiotic resistance, which may affect clinical care and pose a public health risk.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"13"},"PeriodicalIF":4.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}