{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:56:33Z","timestamp":1792673793200,"version":"4.5.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"ICMR-funded project","award":["AMR\/DHR\/GIA\/3\/ECD-II\/2020"],"award-info":[{"award-number":["AMR\/DHR\/GIA\/3\/ECD-II\/2020"]}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001314","name":"SRF","doi-asserted-by":"publisher","award":["113-4297-11330\/2K24\/1"],"award-info":[{"award-number":["113-4297-11330\/2K24\/1"]}],"id":[{"id":"10.13039\/100001314","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Antimicrobial resistance among Enterobacterales is an urgent global crisis, with horizontal gene transfer being one of the major driving forces behind it. The integrons play a significant role in this process. Here, we present the investigation of gene cassette dynamics of integrons among the Enterobacterales under selective antibiotic pressure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We analysed Escherichia coli (n = 214), Klebsiella pneumoniae (n = 210), and Salmonella Typhi (n = 70) isolates for antibiotic susceptibility, and performed Sanger sequencing for the integron region of multidrug-resistant isolates. The evolution assay was carried out to determine the gene cassette rearrangement under stress. RT-qPCR was performed to investigate the gene expression on exposure to trimethoprim and streptomycin. All the E. coli and K. pneumoniae isolates were MDR, and showed the highest resistance to ampicillin (94%) and ceftazidime (95.2%), respectively. Integron screening revealed a higher abundance of class 1 integrons followed by class 2 integrons in both isolates. Sequencing revealed the presence of trimethoprim and streptomycin-resistant gene cassettes within integrons. The phenotypic assays revealed that integron-positive isolates carried more resistance to antibiotics than integron-negative isolates. The combination of 2 antibiotics (trimethoprim + streptomycin) showed gene upregulation in the isolates, depicting the synergistic activity of the antibiotics. The evolution assay revealed a change of the gene cassette arrangement from dfrA12-aadA2 to dfrA17-aadA5 after streptomycin treatment in K. pneumoniae.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The prevalence of integrons thus enhanced the antibiotic resistance, even under antibiotic pressure. These findings highlight the potential role of integrons in antimicrobial resistance among the studied clinical isolates and suggest that monitoring integron-associated resistance may be useful in clinical settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jambio\/lxag135","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T11:39:48Z","timestamp":1780745988000},"source":"Crossref","is-referenced-by-count":1,"title":["Integron-mediated gene cassette dynamics in\n                    <i>Enterobacterales<\/i>\n                    under selective antibiotic pressure"],"prefix":"10.1093","volume":"137","author":[{"given":"Varsha Prakash","family":"Shetty","sequence":"first","affiliation":[{"name":"Nitte (Deemed to be University), Nitte University Centre for Science Education and Research (NUCSER), Department of Infectious Diseases and Microbial Genomics , Paneer Campus, Derlakatte, Mangalore 575018 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Rai","sequence":"additional","affiliation":[{"name":"Nitte (Deemed to be University), Nitte University Centre for Science Education and Research (NUCSER), Department of Infectious Diseases and Microbial Genomics , Paneer Campus, Derlakatte, Mangalore 575018 ,","place":["India"]},{"name":"Nitte (Deemed to be university), KS Hegde Medical Academy (KSHEMA), Department of Microbiology , Deralakatte, Mangalore 575018 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusha","family":"Karunasagar","sequence":"additional","affiliation":[{"name":"Princess Alexandra Hospital Trust Department of Microbiology, , Hamstel Road, Harlow CM20 1QX ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3535-5528","authenticated-orcid":false,"given":"Vijaya Kumar","family":"Deekshit","sequence":"additional","affiliation":[{"name":"Nitte (Deemed to be University), Nitte University Centre for Science Education and Research (NUCSER), Department of Infectious Diseases and Microbial Genomics , Paneer Campus, Derlakatte, Mangalore 575018 ,","place":["India"]},{"name":"Nitte (Deemed to be university), KS Hegde Medical Academy (KSHEMA), Department of Microbiology , Deralakatte, Mangalore 575018 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"2026073010423799300_bib1","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.chom.2024.05.015","article-title":"Antibiotic resistance: a key microbial survival mechanism that threatens public health","volume":"32","author":"Abbas","year":"2024","journal-title":"Cell Host Microbe"},{"key":"2026073010423799300_bib2","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.chom.2024.05.015","article-title":"Antibiotic resistance: A key microbial survival mechanism that threatens public health","volume":"32","author":"Abbas","year":"2024","journal-title":"Cell Host & Microbe"},{"key":"2026073010423799300_bib3","doi-asserted-by":"publisher","first-page":"100081","DOI":"10.1016\/j.glmedi.2024.100081","article-title":"Antimicrobial resistance: impacts, challenges, and future prospects","volume":"2","author":"Ahmed","year":"2024","journal-title":"Journal of Medicine, Surgery, and Public Health"},{"key":"2026073010423799300_bib4","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.1021\/acsinfecdis.3c00408","article-title":"Outer Membrane Proteins and Efflux Pumps Mediated Multi-Drug Resistance in Salmonella: rising Threat to Antimicrobial Therapy","volume":"9","author":"Akshay","year":"2023","journal-title":"ACS Infect Dis"},{"key":"2026073010423799300_bib5","doi-asserted-by":"publisher","first-page":"e02540","DOI":"10.1128\/spectrum.02540-24","article-title":"Comprehensive analysis of extensive drug-resistant Salmonella Typhi in Gujarat region, India: genomic findings and prospective alternative therapy","volume":"13","author":"Akshay","year":"2025","journal-title":"Microbiology Spectrum"},{"key":"2026073010423799300_bib6","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.3390\/microorganisms12122579","article-title":"Integrons in the Age of Antibiotic Resistance: evolution, Mechanisms, and Environmental Implications: a Review","volume":"12","author":"Ali","year":"2024","journal-title":"Microorganisms"},{"key":"2026073010423799300_bib7","doi-asserted-by":"publisher","first-page":"107275","DOI":"10.1016\/j.micpath.2024.107275","article-title":"Emerging threats: Antimicrobial resistance in extended-spectrum beta-lactamase and carbapenem-resistant Escherichia coli","volume":"200","author":"Aljohni","year":"2025","journal-title":"Microbial Pathogenesis"},{"key":"2026073010423799300_bib8","volume-title":"Current protocols in molecular biology","author":"Ausubel","year":"1987"},{"key":"2026073010423799300_bib9","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1128\/jb.02455-14Revert","article-title":"Diversity of class 1 integron gene cassette rear-rangements selected under antibiotic pressure","volume":"197","author":"Barrud","year":"2015","journal-title":"Journal of Bacteriology"},{"key":"2026073010423799300_bib10","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1128\/aem.57.4.1013-1017.1991","article-title":"Detection of Escherichia coli and Shigella spp. in water by using the polymerase chain reaction and gene probes for uidA","volume":"57","author":"Bej","year":"1991","journal-title":"Appl Environ Microb"},{"key":"2026073010423799300_bib11","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1128\/spectrum.00317-23","article-title":"Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics","volume":"11","author":"Bie","year":"2023","journal-title":"Microbiol Spectr"},{"key":"2026073010423799300_bib12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s44259-024-00047-2","article-title":"Drug combinations targeting antibiotic resistance. npj Antimicrob","volume":"2","author":"Bogn\u00e1r","year":"2024","journal-title":"npj Antimicrob Resist"},{"key":"2026073010423799300_bib13","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1093\/nar\/21.9.2260","article-title":"A simple and rapid method for the preparation of gram-negative bacterial genomic DNA","volume":"21","author":"Chen","year":"1993","journal-title":"Nucleic Acids Research"},{"key":"2026073010423799300_bib14","volume-title":"Performance Standards for Antimicrobial Disk Susceptibility Testing, M100S","author":"Clinical and Laboratory Standards Institute","year":"2024","edition":"34th Ed."},{"key":"2026073010423799300_bib15","doi-asserted-by":"publisher","first-page":"211","DOI":"10.4161\/mge.22967","article-title":"Integrons: vehicles and pathways for horizontal dissemination in bacteria","volume":"2","author":"Domingues","year":"2012","journal-title":"Mobile Genetic Elements"},{"key":"2026073010423799300_bib16","doi-asserted-by":"publisher","first-page":"001333","DOI":"10.1099\/mic.0.001333","article-title":"Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors","volume":"169","author":"Gaurav","year":"2023","journal-title":"Microbiology"},{"key":"2026073010423799300_bib17","doi-asserted-by":"crossref","first-page":"269","DOI":"10.61186\/iem.10.4.269","article-title":"Prevalence of Class I Integron Gene in Carbapenem-Resistant Enterobacteriaceae Strains Isolated from Hospitalized Patients","volume":"10","author":"Gholami","year":"2024","journal-title":"IEM"},{"key":"2026073010423799300_bib18","doi-asserted-by":"publisher","first-page":"17025","DOI":"10.1073\/pnas.252607699","article-title":"Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics","volume":"99","author":"Goh","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026073010423799300_bib19","doi-asserted-by":"publisher","first-page":"3826186","DOI":"10.1155\/2020\/3826186","article-title":"Characterization of Integrons and Antimicrobial Resistance in Escherichia coli Sequence Type 131 Isolates","volume":"2020","author":"Huang","year":"2020","journal-title":"Canadian Journal of Infectious Diseases and Medical Microbiology"},{"key":"2026073010423799300_bib20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/cmr.00174-20","article-title":"The changing face of the family enterobacteriaceae (Order: enterobacterales): new members, taxonomic issues, geographic expansion, and new diseases and disease syndromes","volume":"34","author":"Janda","year":"2021","journal-title":"Clin Microbiol Rev"},{"key":"2026073010423799300_bib21","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s12866-025-03794-y","article-title":"Prevalence and characterization of class I integrons in multidrug-resistant Escherichia coli isolates from humans and food-producing animals in Zhejiang Province, China","volume":"25","author":"Jiang","year":"2025","journal-title":"BMC Microbiol"},{"key":"2026073010423799300_bib22","doi-asserted-by":"publisher","first-page":"13","DOI":"10.62550\/BH24010024","article-title":"Antibiotic Resistome, Mobile Genetic Elements, and Virulence Profile of Multidrug-Resistant Enterobacteriaceae Isolated from Healthy Philippine Native Chicken as Revealed by Analysis of Whole Genome Sequence","volume":"108","author":"Jimenez","year":"2025","journal-title":"Philipp Agric Scientist"},{"key":"2026073010423799300_bib23","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.3390\/genes14061212","article-title":"Profiling of Antimicrobial Resistance Genes and Integron from Escherichia coli Isolates Using Whole Genome Sequencing","volume":"14","author":"Joddha","year":"2023","journal-title":"Genes"},{"key":"2026073010423799300_bib24","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.ijantimicag.2017.10.004","article-title":"Integrons in Enterobacteriaceae: diversity, distribution and epidemiology","volume":"51","author":"Kaushik","year":"2018","journal-title":"Int J Antimicrob Agents"},{"key":"2026073010423799300_bib25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0251594","article-title":"\u03b2-lactam resistance associated with \u03b2-lactamase production and porin alteration in clinical isolates of E. coli and K. pneumoniae","volume":"16","author":"Khalifa","year":"2021","journal-title":"PLoS One"},{"key":"2026073010423799300_bib26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12866-024-03250-3","article-title":"Comparison of integron mediated antimicrobial resistance in clinical isolates of Escherichia coli from urinary and bacteremic sources","volume":"24","author":"Kumar","year":"2024","journal-title":"BMC Microbiol"},{"key":"2026073010423799300_bib27","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/978-1-60327-853-9_6","article-title":"The Integron\/Gene Cassette System: an Active Player in Bacterial Adaptation","volume":"532","author":"Labbate","year":"2009","journal-title":"Methods Mol Biol"},{"key":"2026073010423799300_bib28","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2026073010423799300_bib29","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/nrmicro1462","article-title":"Integrons: Agents of bacterial evolution","volume":"4","author":"Mazel","year":"2006","journal-title":"Nature Reviews Microbiology"},{"key":"2026073010423799300_bib30","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.ijmm.2013.07.006","article-title":"The contribution of common rpsL mutations in Escherichia coli to sensitivity to ribosome targeting antibiotics","volume":"303","author":"Pelchovich","year":"2013","journal-title":"Int J Med Microbiol"},{"key":"2026073010423799300_bib31","doi-asserted-by":"publisher","first-page":"760017","DOI":"10.3389\/fmicb.2021.760017","article-title":"Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli","volume":"12","author":"Qi","year":"2021","journal-title":"Front Microbiol"},{"key":"2026073010423799300_bib32","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0890-8508(92)90002-F","article-title":"Amplification of an invA gene sequence of Salmonella typhimurium by polymerase chain reaction as a specific method of detection of Salmonella","volume":"6","author":"Rahn","year":"1992","journal-title":"Mol Cell Probes"},{"key":"2026073010423799300_bib33","doi-asserted-by":"publisher","first-page":"560","DOI":"10.3855\/jidc.18973","article-title":"Genetic characterization of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae collected from healthy turkeys","volume":"19","author":"Romdhani","year":"2025","journal-title":"J Infect Dev Ctries"},{"key":"2026073010423799300_bib34","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1093\/jambio\/lxad137","article-title":"Integrons as the potential targets for combating multidrug resistance in Enterobacteriaceae using CRISPR- Cas9 technique","volume":"134","author":"Shetty","year":"2023","journal-title":"J Appl Microbiol"},{"key":"2026073010423799300_bib35","doi-asserted-by":"publisher","first-page":"6203","DOI":"10.2147\/IDR.S385411","article-title":"Effect of Colistin, Fosfomycin and Meropenem\/Vaborbactam on Carbapenem-Resistant Enterobacterales in Egypt: a Cross-Sectional Study","volume":"15","author":"Shrief","year":"2022","journal-title":"IDR"},{"key":"2026073010423799300_bib36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10482-025-02103-x","article-title":"Integrons: the hidden architects of bacterial adaptation, evolution, and the challenges of antimicrobial resistance","volume":"118","author":"Singh","year":"2025","journal-title":"Antonie Van Leeuwenhoek"},{"key":"2026073010423799300_bib37","doi-asserted-by":"publisher","first-page":"236549","DOI":"10.3389\/fmicb.2017.00561","article-title":"Distribution of integrons and phylogenetic groups among enteropathogenic Escherichia coli isolates from children &lt; 5 Years of Age in Delhi, India","volume":"8","author":"Singh","year":"2017","journal-title":"Front Microbiol"},{"key":"2026073010423799300_bib38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.62474","article-title":"Integron activity accelerates the evolution of antibiotic resistance","volume":"10","author":"Souque","year":"2021","journal-title":"eLife"},{"key":"2026073010423799300_bib39","doi-asserted-by":"publisher","first-page":"W74","DOI":"10.1093\/nar\/gkm306","article-title":"Primer3Plus, an enhanced web interface to Primer3","volume":"35","author":"Untergasser","year":"2007","journal-title":"Nucleic Acids Research"},{"key":"2026073010423799300_bib40","doi-asserted-by":"publisher","first-page":"wrad032","DOI":"10.1093\/ismejo\/wrad032","article-title":"Inter-plasmid transfer of antibiotic resistance genes accelerates antibiotic resistance in bacterial pathogens","volume":"18","author":"Wang","year":"2024","journal-title":"ISME J"},{"key":"2026073010423799300_bib41","doi-asserted-by":"publisher","first-page":"801292","DOI":"10.3389\/fmicb.2021.801292","article-title":"High Prevalence of Antimicrobial Resistance and Integron Gene Cassettes in Multi-Drug-Resistant Klebsiella pneumoniae Isolates from Captive Giant Pandas (Ailuropoda melanoleuca)","volume":"12","author":"Yan","year":"2022","journal-title":"Front Microbiol"},{"key":"2026073010423799300_bib42","doi-asserted-by":"publisher","first-page":"5429","DOI":"10.1128\/jcm.41.12.5429-5433.2003","article-title":"Changes in Gene Cassettes of Class 1 Integrons among Escherichia coli Isolates from Urine Specimens Collected in Korea during the Last Two Decades","volume":"41","author":"Yu","year":"2003","journal-title":"Journal of Clinical Microbiology"},{"key":"2026073010423799300_bib43","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/antibiotics15010037","article-title":"Antibiotic Resistance in Klebsiella pneumoniae and Related Enterobacterales: Molecular Mechanisms, Mobile Elements, and Therapeutic Challenges","volume":"15","author":"Zdarska","year":"2026","journal-title":"Antibiotics"}],"container-title":["Journal of Applied Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jambio\/advance-article-pdf\/doi\/10.1093\/jambio\/lxag135\/68488930\/lxag135.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/137\/6\/lxag135\/68488930\/lxag135.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/137\/6\/lxag135\/68488930\/lxag135.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:42:42Z","timestamp":1785422562000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jambio\/article\/doi\/10.1093\/jambio\/lxag135\/8703831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jambio\/lxag135","relation":{},"ISSN":["1365-2672"],"issn-type":[{"value":"1365-2672","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,6]]},"article-number":"lxag135"}}