{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:55:09Z","timestamp":1791381309742,"version":"4.3.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["19DZ2202600"],"award-info":[{"award-number":["19DZ2202600"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970128"],"award-info":[{"award-number":["31970128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFE0102100"],"award-info":[{"award-number":["2018YFE0102100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Modules consisting of antibiotic resistance genes (ARGs) flanked by inverted repeat Xer-specific recombination sites were thought to be mobile genetic elements that promote horizontal transmission. Less frequently, the presence of mobile modules in plasmids, which facilitate a pdif-mediated ARGs transfer, has been reported. Here, numerous ARGs and toxin-antitoxin genes have been found in pdif site pairs. However, the mechanisms underlying this apparent genetic mobility is currently not understood, and the studies relating to pdif-mediated ARGs transfer onto most bacterial genera are lacking. We developed the web server pdifFinder based on an algorithm called PdifSM that allows the prediction of diverse pdif-ARGs modules in bacterial genomes. Using test set consisting of almost 32 thousand plasmids from 717 species, PdifSM identified 481 plasmids from various bacteria containing pdif sites with ARGs. We found 28-bp-long elements from different genera with clear base preferences. The data we obtained indicate that XerCD-dif site-specific recombination mechanism may have evolutionary adapted to facilitate the pdif-mediated ARGs transfer. Through multiple sequence alignment and evolutionary analyses of duplicated pdif-ARGs modules, we discovered that pdif sites allow an interspecies transfer of ARGs but also across different genera. Mutations in pdif sites generate diverse arrays of modules which mediate multidrug-resistance, as these contain variable numbers of diverse ARGs, insertion sequences and other functional genes. The identification of pdif-ARGs modules and studies focused on the mechanism of ARGs co-transfer will help us to understand and possibly allow controlling the spread of MDR bacteria in clinical settings. The pdifFinder code, standalone software package and description with tutorials are available at https:\/\/github.com\/mjshao06\/pdifFinder.<\/jats:p>","DOI":"10.1093\/bib\/bbac521","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T05:24:59Z","timestamp":1670304299000},"source":"Crossref","is-referenced-by-count":23,"title":["P<i>dif<\/i>-mediated antibiotic resistance genes transfer in bacteria identified by pdifFinder"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6624-978X","authenticated-orcid":false,"given":"Mengjie","family":"Shao","sequence":"first","affiliation":[{"name":"Hangzhou Dianzi University School of Automation, , Hangzhou, Zhejiang, 310018, P R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanjiao","family":"Ying","sequence":"additional","affiliation":[{"name":"Hangzhou Dianzi University School of Automation, , Hangzhou, Zhejiang, 310018, P R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liang","sequence":"additional","affiliation":[{"name":"Hangzhou Digital Micro Biotech Co., Ltd. , Hangzhou, 311215 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Ma","sequence":"additional","affiliation":[{"name":"Hangzhou Dianzi University School of Automation, , Hangzhou, Zhejiang, 310018, P R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-4622","authenticated-orcid":false,"given":"Sebastian","family":"Leptihn","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine Department of Infectious Diseases, Sir Run Run Shaw Hospital, , Hangzhou, Zhejiang, 310016, P R China"},{"name":"School of Medicine, Zhejiang University Zhejiang University-University of Edinburgh Institute, , Hangzhou , China"},{"name":"The University of Edinburgh University of Edinburgh Medical School, Biomedical Sciences, College of Medicine and Veterinary Medicine, , Edinburgh , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsong","family":"Yu","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine Department of Infectious Diseases, Sir Run Run Shaw Hospital, , Hangzhou, Zhejiang, 310016, P R China"},{"name":"Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province , Hangzhou, Zhejiang, 310016, P R China"},{"name":"Zhejiang University School of Medicine Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, , Hangzhou, Zhejiang, 310016, P R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8005-5690","authenticated-orcid":false,"given":"Huan","family":"Chen","sequence":"additional","affiliation":[{"name":"Hangzhou Digital Micro Biotech Co., Ltd. , Hangzhou, 311215 , China"},{"name":"Zhejiang Chinese Medical University College of Life Science, , Hangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Hangzhou Digital Micro Biotech Co., Ltd. , Hangzhou, 311215 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-916X","authenticated-orcid":false,"given":"Xiaoting","family":"Hua","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine Department of Infectious Diseases, Sir Run Run Shaw Hospital, , Hangzhou, Zhejiang, 310016, P R China"},{"name":"Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province , Hangzhou, Zhejiang, 310016, P R China"},{"name":"Zhejiang University School of Medicine Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, , Hangzhou, Zhejiang, 310016, P R China"},{"name":"Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"2023011917141593500_ref1","doi-asserted-by":"crossref","first-page":"S397","DOI":"10.1093\/cid\/cir153","article-title":"IDSA Public Policy: Combating Antimicrobial Resistance: Policy Recommendations to SaveLives","volume":"52","author":"Spellberg","year":"2011","journal-title":"Clin Infect Dis An Off Publ Infect Dis Soc Am"},{"key":"2023011917141593500_ref2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nrd3013","article-title":"Anti-virulence strategies to combat bacteria-mediated disease","volume":"9","author":"Rasko","year":"2010","journal-title":"Nat Rev Drug Discov"},{"key":"2023011917141593500_ref3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/595011","article-title":"Bad bugs, no drugs: No ESKAPE! An update from the Infectious Diseases Society of America","volume":"48","author":"Boucher","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2023011917141593500_ref4","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1093\/jac\/dku486","article-title":"Carbapenem and amikacin resistance on a large conjugative Acinetobacter baumannii plasmid","volume":"70","author":"Nigro","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"2023011917141593500_ref5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.00780-17","article-title":"The tet39 Determinant and the msrE-mphE Genes in Acinetobacter Plasmids Are Each Part of Discrete Modules Flanked by Inversely Oriented pdif (XerC-XerD) Sites","volume":"61","author":"Blackwell","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2023011917141593500_ref6","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1111\/j.1574-6976.2011.00273.x","article-title":"Gene flow, mobile genetic 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