{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:44:38Z","timestamp":1790102678164,"version":"4.0.1"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T00:00:00Z","timestamp":1737763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"DZIF-R-Net 2.0 project, TTU 08.824","doi-asserted-by":"publisher","award":["8032808824"],"award-info":[{"award-number":["8032808824"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"DZIF-R-Net 2.0 project, TTU 08.824","doi-asserted-by":"publisher","award":["V3B"],"award-info":[{"award-number":["V3B"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SurvCARE, Hessian Ministry for Social Affairs and Integration","award":["8032808824"],"award-info":[{"award-number":["8032808824"]}]},{"name":"SurvCARE, Hessian Ministry for Social Affairs and Integration","award":["V3B"],"award-info":[{"award-number":["V3B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Proteus mirabilis is a well-known opportunistic pathogen predominantly associated with urinary tract infections. It exhibits natural resistance to multiple antibiotics, including last-resort options like colistin. The emergence and spread of multidrug-resistant P. mirabilis isolates, including those producing ESBLs, AmpC cephalosporinases, and carbapenemases, are now more frequently reported. The most common carbapenemase types found in P. mirabilis are KPC-2, IMP, VIM, NDM, and OXA-48. We sequenced the genomes of three carbapenem-resistant P. mirabilis isolates harboring both blaVIM-4 and blaVIM-75 from Germany using both short-read and long-read sequencing techniques. We found that the isolates were only distantly related genetically. Both blaVIM-4 and blaVIM-75 genes were located on a class I integron, which in two cases was located on the chromosome and in one case on a plasmid. This is the first report on the complete genomes of P. mirabilis strains harboring a rare genetic element encoding both blaVIM-4 and blaVIM-75. Our results emphasize a key role for class 1 integrons in the transmission of VIM carbapenemases in P. mirabilis.<\/jats:p>","DOI":"10.3390\/microorganisms13020266","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T06:39:51Z","timestamp":1737959991000},"page":"266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Detection of Extensively Drug-Resistant Proteus mirabilis Strains Harboring Both VIM-4 and VIM-75 Metallo-\u03b2-Lactamases from Patients in Germany"],"prefix":"10.3390","volume":"13","author":[{"given":"Moritz","family":"Fritzenwanker","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2949-3166","authenticated-orcid":false,"given":"Jane","family":"Falgenhauer","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany"},{"name":"Institute for Hygiene and Environmental Medicine, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Hain","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Imirzalioglu","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1452-4759","authenticated-orcid":false,"given":"Trinad","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8553-1569","authenticated-orcid":false,"given":"Yancheng","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/ecosalplus.esp-0009-2017","article-title":"Pathogenesis of Proteus mirabilis Infection","volume":"8","author":"Armbruster","year":"2018","journal-title":"EcoSal Plus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1099\/ijs.0.021964-0","article-title":"Phylogenetic analysis of the genera Proteus, Morganella and Providencia by comparison of rpoB gene sequences of type and clinical strains suggests the reclassification of Proteus myxofaciens in a new genus, Cosenzaea gen. nov., as Cosenzaea myxofaciens comb. nov","volume":"61","author":"Giammanco","year":"2011","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1128\/JB.01981-07","article-title":"Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility","volume":"190","author":"Pearson","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Schaffer, J.N., and Pearson, M.M. (2015). Proteus mirabilis and Urinary Tract Infections. Urinary Tract Infections: Molecular Pathogenesis and Clinical Management, Wiley.","DOI":"10.1128\/microbiolspec.UTI-0017-2013"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1179\/joc.2003.15.1.12","article-title":"Natural antibiotic susceptibility of Proteus spp., with special reference to P. mirabilis and P. penneri strains","volume":"15","author":"Stock","year":"2003","journal-title":"J. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Girlich, D., Bonnin, R.A., Dortet, L., and Naas, T. (2020). Genetics of Acquired Antibiotic Resistance Genes in Proteus spp.. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00256"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/j.1469-0691.2006.01489.x","article-title":"Emergence of Proteus mirabilis carrying the blaVIM-1 metallo-\u03b2-lactamase gene","volume":"12","author":"Vourli","year":"2006","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1089\/mdr.2016.0026","article-title":"Dissemination of a multidrug-resistant VIM-1- and CMY-99-producing Proteus mirabilis clone in Bulgaria","volume":"23","author":"Markovska","year":"2017","journal-title":"Microb. Drug Resist."},{"key":"ref_9","unstructured":"Robert Koch-Institut (2023). Bericht des Nationalen Referenzzentrums f\u00fcr Gramnegative Krankenhauserreger, Robert Koch-Institut."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yao, Y., Imirzalioglu, C., Falgenhauer, L., Falgenhauer, J., Heinm\u00fcller, P., Domann, E., and Chakraborty, T. (2024). Plasmid-Mediated Spread of Carbapenem Resistance in Enterobacterales: A Three-Year Genome-Based Survey. Antibiotics, 13.","DOI":"10.3390\/antibiotics13080682"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yao, Y., Doijad, S., Falgenhauer, J., Schmiedel, J., Imirzalioglu, C., and Chakraborty, T. (2022). Co-occurrence of dual carbapenemases KPC-2 and OXA-48 with the mobile colistin resistance gene mcr-9.1 in Enterobacter xiangfangensis. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.960892"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Schwengers, O., Hoek, A., Fritzenwanker, M., Falgenhauer, L., Hain, T., Chakraborty, T., and Goesmann, A. (2020). ASA3P: An automatic and scalable pipeline for the assembly, annotation and higher level analysis of closely related bacterial isolates. PLoS Comput. Biol., 16.","DOI":"10.1371\/journal.pcbi.1007134"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1128\/AAC.02412-14","article-title":"In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing","volume":"58","author":"Carattoli","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1093\/jac\/dks261","article-title":"Identification of acquired antimicrobial resistance genes","volume":"67","author":"Zankari","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"D32","DOI":"10.1093\/nar\/gkj014","article-title":"ISfinder: The reference centre for bacterial insertion sequences","volume":"34","author":"Siguier","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/14756366.2017.1344235","article-title":"Beta-lactamase database (BLDB)\u2013structure and function","volume":"32","author":"Naas","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"W229","DOI":"10.1093\/nar\/gky352","article-title":"OriTfinder: A web-based tool for the identification of origin of transfers in DNA sequences of bacterial mobile genetic elements","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/jac\/dkaa390","article-title":"Detection of mobile genetic elements associated with antibiotic resistance in Salmonella enterica using a newly developed web tool: MobileElementFinder","volume":"76","author":"Johansson","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/jac\/dkx513","article-title":"Automated annotation of mobile antibiotic resistance in Gram-negative bacteria: The Multiple Antibiotic Resistance Annotator (MARA) and database","volume":"73","author":"Partridge","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"W246","DOI":"10.1093\/nar\/gky425","article-title":"CRISPRCasFinder, an update of CRISRFinder, includes a portable version, enhanced performance and integrates search for Cas proteins","volume":"46","author":"Couvin","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.2174\/1389450116666151001105622","article-title":"B1-Metallo-\u03b2-Lactamases: Where Do We Stand?","volume":"17","author":"Mojica","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fuchs, F., Ahmadzada, A., Plambeck, L., Wille, T., and Hamprecht, A. (2021). Susceptibility of Clinical Enterobacterales Isolates With Common and Rare Carbapenemases to Mecillinam. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.627267"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Heiden, S.E., Sydow, K., Schaefer, S., Klempien, I., Balau, V., Bauer, P., H\u00fcbner, N.O., and Schaufler, K. (2021). Nearly identical plasmids encoding vim-1 and mercury resistance in enterobacteriaceae from north-eastern germany. Microorganisms, 9.","DOI":"10.3390\/microorganisms9071345"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.jgar.2021.03.027","article-title":"First report of a blaVIM-1 metallo-\u03b2-lactamase-possessing Klebsiella michiganensis","volume":"25","author":"Sigrist","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4024","DOI":"10.1128\/AAC.00470-12","article-title":"Characterization of a transmissible plasmid encoding VEB-1 and VIM-1 in Proteus mirabilis","volume":"56","author":"Papagiannitsis","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/1469-0691.12322","article-title":"A disc diffusion assay for detection of class A, B and OXA-48 carbapenemases in Enterobacteriaceae using phenyl boronic acid, dipicolinic acid and temocillin","volume":"20","author":"Voets","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106060","DOI":"10.1016\/j.ijantimicag.2020.106060","article-title":"Clonal outbreak caused by VIM-4-producing Proteus mirabilis in a Greek tertiary-care hospital","volume":"56","author":"Protonotariou","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6594","DOI":"10.1128\/AAC.00400-15","article-title":"Non-O1\/non-O139 Vibrio cholerae avian isolate from France cocarrying the blaVIM-1 and blaVIM-4 genes","volume":"59","author":"Aberkane","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1089\/mdr.2018.0365","article-title":"Increased resistance to carbapenems in Proteus mirabilis mediated by amplification of the blaVIM-1-carrying and IS26-associated class 1 integron","volume":"25","author":"Bontron","year":"2019","journal-title":"Microb. Drug Resist."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ijantimicag.2004.11.012","article-title":"Alterations in the GyrA and GyrB subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa","volume":"25","author":"Lee","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Varughese, L.R., Rajpoot, M., Goyal, S., Mehra, R., Chhokar, V., and Beniwal, V. (2018). Analytical profiling of mutations in quinolone resistance determining region of gyrA gene among UPEC. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190729"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.12669\/pjms.36.6.2207","article-title":"Dna gyrase and topoisomerase iv mutations and their effect on quinolones resistant Proteus mirabilis among utis patients","volume":"36","author":"Abdelkreem","year":"2020","journal-title":"Pak. J. Med. Sci."},{"key":"ref_34","first-page":"41","article-title":"Mutations of DNA gyrase and topoisomerase IV in clinical isolates of fluoroquinolone-resistant Proteus mirabilis","volume":"59","author":"Saito","year":"2006","journal-title":"Jpn. J. Antibiot."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bitar, I., Marchetti, V.M., Mercato, A., Nucleo, E., Anesi, A., Bracco, S., Rognoni, V., Hrabak, J., and Migliavacca, R. (2020). Complete genome and plasmids sequences of a clinical Proteus mirabilis isolate producing plasmid mediated ndm-1 from Italy. Microorganisms, 8.","DOI":"10.3390\/microorganisms8030339"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/2\/266\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:36:00Z","timestamp":1759919760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/2\/266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,25]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["microorganisms13020266"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13020266","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,25]]}}}