{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:08:44Z","timestamp":1778576924709,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22K08606"],"award-info":[{"award-number":["22K08606"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Carbapenemase-producing Enterobacterales (CPE) is a global threat. IMP-6, a prevalent carbapenemase in western Japan, is mostly disseminated via CTX-M-2 extended-spectrum \u03b2-lactamase (ESBL) co-producing Enterobacterales. However, the existence and characteristics of Enterobacterales harboring blaIMP-6 without blaCTX-M-2 remain unclear. We analyzed the phenotypic and genetic characteristics of clinical blaIMP-6-harboring Enterobacterales isolates, focusing on those lacking blaCTX-M-2. Overall, 220 blaIMP-6-harboring isolates collected from 76 Japanese hospitals between 2014 and 2021 were characterized by antimicrobial susceptibility, presence of CTX-M-type ESBLs, plasmid incompatibility, plasmid transfer experiments, and genome sequencing and analysis. Among these, 203 co-harbored blaCTX-M-2 group, with 90% of them demonstrating high conjugation frequency and broad-spectrum resistance to \u03b2-lactams. Of the remaining 17 isolates, nine lacked blaCTX-M, while eight co-harbored blaCTX-M-1 group (n = 2) or blaCTX-M-9 group (n = 6). Eleven isolates carried nontransferable plasmids with genetic structures distinct from those of blaIMP-6 and blaCTX-M-2 co-encoding plasmids, including eight non-incompatibility N plasmids. Fifteen isolates carried only blaIMP-6-encoding plasmids; two carried plasmids with blaIMP-6 and blaCTX-M (blaCTX-M-27 or blaCTX-M-65). This novel study revealed that blaIMP-6 can exist without blaCTX-M-2 on diverse, often nontransferable plasmids, suggesting distinct, lower dissemination pathways compared to those of epidemic blaCTX-M-2 co-carrying plasmids and highlighting previously overlooked plasmids that necessitate close monitoring.<\/jats:p>","DOI":"10.3390\/ijms27104269","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic and Genetic Characteristics of blaIMP-6-Harboring Enterobacterales Isolates Lacking blaCTX-M-2 in Japan"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5905-7887","authenticated-orcid":false,"given":"Koichi","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-2591","authenticated-orcid":false,"given":"Ryuichi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiyo","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rio","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mako","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuji","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, BML Inc., 1361-1 Matoba, Kawagoe 3501101, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, BML Inc., 1361-1 Matoba, Kawagoe 3501101, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisakazu","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Moreira de Gouveia, M.I., Bernalier-Donadille, A., and Jubelin, G. (2024). Enterobacteriaceae in the human gut: Dynamics and ecological roles in health and disease. Biology, 13.","DOI":"10.3390\/biology13030142"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rabaan, A.A., Eljaaly, K., Alhumaid, S., Albayat, H., Al-Adsani, W., Sabour, A.A., Alshiekheid, M.A., Al-Jishi, J.M., Khamis, F., and Alwarthan, S. (2022). An overview on phenotypic and genotypic characterisation of carbapenem-resistant Enterobacterales. Medicina, 58.","DOI":"10.3390\/medicina58111675"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13756-022-01053-7","article-title":"Prevalence and characterization of antimicrobial resistance among gram-negative bacteria isolated from febrile hospitalized patients in central Ethiopia","volume":"11","author":"Tufa","year":"2022","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"127249","DOI":"10.1016\/j.micres.2022.127249","article-title":"Global spread of carbapenem-resistant Enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy","volume":"266","author":"Ma","year":"2023","journal-title":"Microbiol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Suay-Garc\u00eda, B., and P\u00e9rez-Gracia, M.T. (2019). Present and future of carbapenem-resistant Enterobacteriaceae (CRE) infections. Antibiotics, 8.","DOI":"10.3390\/antibiotics8030122"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Eichenberger, E.M., and Thaden, J.T. (2019). Epidemiology and mechanisms of resistance of extensively drug resistant gram-negative bacteria. Antibiotics, 8.","DOI":"10.3390\/antibiotics8020037"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00759-20","DOI":"10.1128\/mSystems.00759-20","article-title":"Characterization of the plasmidome encoding carbapenemase and mechanisms for dissemination of carbapenem-resistant Enterobacteriaceae","volume":"5","author":"Abe","year":"2020","journal-title":"mSystems"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41467-025-66874-7","article-title":"The rise and global spread of IMP carbapenemases (1996-2023): A genomic epidemiology study","volume":"17","author":"Vezina","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1128\/AAC.39.4.824","article-title":"Plasmid-mediated dissemination of the metallo-beta-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens","volume":"39","author":"Ito","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1128\/AAC.00617-12","article-title":"High frequency of IMP-6 among clinical isolates of metallo-\u03b2-lactamase-producing Escherichia coli in Japan","volume":"56","author":"Yano","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hirabayashi, A., Yahara, K., Kajihara, T., Sugai, M., and Shibayama, K. (2020). Geographical distribution of Enterobacterales with a carbapenemase IMP-6 phenotype and its association with antimicrobial use: An analysis using comprehensive national surveillance data on antimicrobial resistance. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0243630"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1128\/AAC.45.5.1343-1348.2001","article-title":"Plasmid-encoded metallo-beta-lactamase (IMP-6) conferring resistance to carbapenems, especially meropenem","volume":"45","author":"Yano","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jiac.2016.12.013","article-title":"Molecular epidemiology of carbapenemase-producing Enterobacteriaceae in a primary care hospital in Japan, 2010\u20132013","volume":"23","author":"Ohno","year":"2017","journal-title":"J. Infect. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.diagmicrobio.2011.09.019","article-title":"Emergence in Japan of an imipenem-susceptible, meropenem-resistant Klebsiella pneumoniae carrying blaIMP-6","volume":"72","author":"Shigemoto","year":"2012","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"dlae135","DOI":"10.1093\/jacamr\/dlae135","article-title":"Prevalence of carbapenem-resistant Enterobacterales with blaIMP-6 predominance in hospitals from 2018 to 2021 in Nara, Japan","volume":"6","author":"Kishi","year":"2024","journal-title":"JAC-Antimicrob. Resist."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1128\/AAC.04759-14","article-title":"Complete nucleotide sequence of the IncN plasmid encoding IMP-6 and CTX-M-2 from emerging carbapenem-resistant Enterobacteriaceae in Japan","volume":"59","author":"Kayama","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ijantimicag.2011.11.018","article-title":"Dissemination of genetically related IMP-6-producing multidrug-resistant Pseudomonas aeruginosa ST235 in South Korea","volume":"39","author":"Yoo","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.diagmicrobio.2008.08.019","article-title":"Outbreak by meropenem-resistant Pseudomonas aeruginosa producing IMP-6 metallo-beta-lactamase in a Korean hospital","volume":"63","author":"Ryoo","year":"2009","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s10096-014-2063-5","article-title":"Dissemination of IMP-6-producing Pseudomonas aeruginosa ST244 in multiple cities in China","volume":"33","author":"Chen","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_20","first-page":"414","article-title":"Prevalence and genetic analysis of multidrug-resistant Pseudomonas aeruginosa ST235 isolated from a hospital in Korea, 2008\u20132012","volume":"43","author":"Cho","year":"2013","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jb\/mvac080","article-title":"Structural insights into the substrate specificity of IMP-6 and IMP-1 metallo-\u03b2-lactamases","volume":"173","author":"Yamamoto","year":"2022","journal-title":"J. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ogawa, Y., Nakano, R., Kasahara, K., Mizuno, T., Hirai, N., Nakano, A., Suzuki, Y., Kakuta, N., Masui, T., and Yano, H. (2019). Comparison of the inoculum size effects of antibiotics on IMP-6 beta-lactamase-producing Enterobacteriaceae co-harboring plasmid-mediated quinolone resistance genes. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225210"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1038\/s41598-020-60659-2","article-title":"A prolonged multispecies outbreak of IMP-6 carbapenemase-producing Enterobacterales due to horizontal transmission of the IncN plasmid","volume":"10","author":"Yamagishi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"dlab092","DOI":"10.1093\/jacamr\/dlab092","article-title":"Extended-spectrum \u03b2-lactamases: An update on their characteristics, epidemiology and detection","volume":"3","author":"Castanheira","year":"2021","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1093\/jac\/dkx146","article-title":"Global epidemiology of CTX-M \u03b2-lactamases: Temporal and geographical shifts in genotype","volume":"72","author":"Bevan","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","unstructured":"CLSI (2025). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [35th ed.]. CLSI supplement M100."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1093\/jac\/dkv017","article-title":"CTX-M-27- and CTX-M-14-producing, ciprofloxacin-resistant Escherichia coli of the H30 subclonal group within ST131 drive a Japanese regional ESBL epidemic","volume":"70","author":"Matsumura","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.3201\/eid2211.160519","article-title":"Global Escherichia coli sequence type 131 clade with blaCTX-M-27 Gene","volume":"22","author":"Matsumura","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8046","DOI":"10.1038\/s41467-023-43516-4","article-title":"National genomic surveillance integrating standardized quantitative susceptibility testing clarifies antimicrobial resistance in Enterobacterales","volume":"14","author":"Kayama","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhin.2017.07.015","article-title":"Prevalence of, and risk factors for, carriage of carbapenem-resistant Enterobacteriaceae among hospitalized patients in Japan","volume":"97","author":"Yamamoto","year":"2017","journal-title":"J. Hosp. Infect."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1093\/jac\/dkr225","article-title":"Multilocus sequence typing of IncN plasmids","volume":"66","author":"Villa","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.7164\/antibiotics.52.1135","article-title":"Presence of genes for beta-lactamases of two different classes on a single plasmid from a clinical isolate of Serratia marcescens","volume":"52","author":"Yano","year":"1999","journal-title":"J. Antibiot."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00490-20","DOI":"10.1128\/mSphere.00490-20","article-title":"Molecular and epidemiological characteristics of carbapenemase-producing Klebsiella pneumoniae clinical isolates in Japan","volume":"5","author":"Yonekawa","year":"2020","journal-title":"mSphere"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.diagmicrobio.2009.02.004","article-title":"Clinical outcomes of patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae after treatment with imipenem or meropenem","volume":"64","author":"Weisenberg","year":"2009","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"378","DOI":"10.3343\/alm.2018.38.4.378","article-title":"Rapid identification of blaIMP-1 and blaIMP-6 by multiplex amplification refractory mutation system PCR","volume":"38","author":"Nakano","year":"2018","journal-title":"Ann. Lab. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6647","DOI":"10.2147\/IDR.S559992","article-title":"Loop-Mediated Isothermal Amplification (LAMP) for Rapid and Sensitive Detection of Carbapenemase Genes in CRE: A Diagnostic Validation Study","volume":"18","author":"Gou","year":"2025","journal-title":"Infect. Drug Resist."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Segawa, T., Sekizuka, T., Suzuki, S., Shibayama, K., Matsui, M., and Kuroda, M. (2018). The plasmid-encoded transcription factor ArdK contributes to the repression of the IMP-6 metallo-\u03b2-lactamase gene blaIMP-6, leading to a carbapenem-susceptible phenotype in the blaIMP-6-positive Escherichia coli strain A56-1S. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208976"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"dlad106","DOI":"10.1093\/jacamr\/dlad106","article-title":"Analysis of the stepwise acquisition of blaCTX-M-2 and subsequent acquisition of either blaIMP-1 or blaIMP-6 in highly conserved IncN-pST5 plasmids","volume":"5","author":"Ikegaya","year":"2023","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13100-021-00239-x","article-title":"The IS6 family, a clinically important group of insertion sequences including IS26","volume":"12","author":"Varani","year":"2021","journal-title":"Mob. DNA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00202-20","DOI":"10.1128\/AAC.00202-20","article-title":"Characterization of blaCTX-M-27\/F1:A2:B20 plasmids harbored by Escherichia coli sequence type 131 sublineage C1\/H30R isolates spreading among elderly Japanese in nonacute-care settings","volume":"64","author":"Matsuo","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/jac\/dkg256","article-title":"Effect of D240G substitution in a novel ESBL CTX-M-27","volume":"52","author":"Bonnet","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"van der Zwaluw, K., de Haan, A., Pluister, G.N., Bootsma, H.J., de Neeling, A.J., and Schouls, L.M. (2015). The carbapenem inactivation method (CIM), a simple and low-cost alternative for the Carba NP test to assess phenotypic carbapenemase activity in gram-negative rods. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123690"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/jac\/dkp498","article-title":"Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae","volume":"65","author":"Dallenne","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1128\/AAC.48.4.1151-1158.2004","article-title":"CFE-1, a novel plasmid-encoded AmpC beta-lactamase with an ampR gene originating from Citrobacter freundii","volume":"48","author":"Nakano","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Alderliesten, J.B., Duxbury, S.J.N., Zwart, M.P., de Visser, J., Stegeman, A., and Fischer, E.A.J. (2020). Effect of donor-recipient relatedness on the plasmid conjugation frequency: A meta-analysis. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-01825-4"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.mimet.2005.03.018","article-title":"Identification of plasmids by PCR-based replicon typing","volume":"63","author":"Carattoli","year":"2005","journal-title":"J. Microbiol. Methods"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wick, R.R., Judd, L.M., Gorrie, C.L., and Holt, K.E. (2017). Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005595"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/bioinformatics\/btx713","article-title":"DFAST: A flexible prokaryotic genome annotation pipeline for faster genome publication","volume":"34","author":"Tanizawa","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"173","DOI":"10.12938\/bmfh.16-003","article-title":"DFAST and DAGA: Web-based integrated genome annotation tools and resources","volume":"35","author":"Tanizawa","year":"2016","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1093\/jac\/dkaa345","article-title":"ResFinder 4.0 for predictions of phenotypes from genotypes","volume":"75","author":"Bortolaia","year":"2020","journal-title":"J. Antimicrob. Chemother."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4269\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:11:55Z","timestamp":1778573515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104269"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104269","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]}}}