{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:41:01Z","timestamp":1784547661275,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"48","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["436573923"],"award-info":[{"award-number":["436573923"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["MI 684\/7\u20101"],"award-info":[{"award-number":["MI 684\/7\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["OH 97\/8\u20101"],"award-info":[{"award-number":["OH 97\/8\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["390838134"],"award-info":[{"award-number":["390838134"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibiotic\u2010resistant enterococci represent a significant global health challenge. Unfortunately, most \u03b2\u2010lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides are conjugated to examples from each of the four classes of \u03b2\u2010lactam antibiotics. Remarkably, the \u03b2\u2010lactam\u2013peptide conjugates gained an up to 1000\u2010fold increase in antimicrobial activity against vancomycin\u2010susceptible and vancomycin\u2010resistant enterococci. Even against \u03b2\u2010lactam\u2010resistant Gram\u2010negative strains, the conjugates are found to be effective despite their size exceeding the exclusion volume of porins. The extraordinary gain of activity can be explained by an altered mode of killing. Of note, the conjugates showed a concentration\u2010dependent activity in contrast to the parent \u03b2\u2010lactam antibiotics that exhibited a time\u2010dependent mode of action. In comparison to the parent \u03b2\u2010lactams, the conjugates showed altered affinities to the penicillin\u2010binding proteins. Furthermore, it is found that peptide conjugation also resulted in a different elimination route of the compounds when administered to rodents. In mice systemically infected with vancomycin\u2010resistant enterococci, treatment with a \u03b2\u2010lactam\u2013peptide conjugate reduced bacterial burden in the liver compared to its originator. Therefore, peptide modification of \u03b2\u2013lactam antibiotics represents a promising platform strategy to broaden their efficacy spectrum, particularly against enterococci.<\/jats:p>","DOI":"10.1002\/advs.202411406","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T13:40:32Z","timestamp":1730814032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Conjugation of Polycationic Peptides Extends the Efficacy Spectrum of \u03b2\u2010Lactam Antibiotics"],"prefix":"10.1002","volume":"11","author":[{"given":"Julia","family":"Werner","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Umst\u00e4tter","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel B.","family":"B\u00f6hmann","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy and Molecular Biotechnology Heidelberg University  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Microbial Bioactive Compounds Interfaculty Institute of Microbiology and Infection Medicine University of T\u00fcbingen  72076 T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbro","family":"Beijer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Hertlein","sequence":"additional","affiliation":[{"name":"Institute of Molecular Infection Biology University of W\u00fcrzburg  97080 W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kaschnitz","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Bram","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kleist","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel D.","family":"Klika","sequence":"additional","affiliation":[{"name":"NMR Spectroscopy Analysis Unit German Cancer Research Center (DKFZ)  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"M\u00fchlberg","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy and Molecular Biotechnology Heidelberg University  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Braune","sequence":"additional","affiliation":[{"name":"Institute of Molecular Infection Biology University of W\u00fcrzburg  97080 W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Wohlfart","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Bioorganic Chemistry Institute of Pharmacy and Molecular Biotechnology Heidelberg University  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Peter","sequence":"additional","affiliation":[{"name":"Medical Microbiology Interfaculty Institute of Microbiology and Infection Medicine University of T\u00fcbingen  72076 T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Medical Microbiology and Hygiene Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Haberkorn","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Ohlsen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Infection Biology University of W\u00fcrzburg  97080 W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Br\u00f6tz\u2010Oesterhelt","sequence":"additional","affiliation":[{"name":"Microbial Bioactive Compounds Interfaculty Institute of Microbiology and Infection Medicine University of T\u00fcbingen  72076 T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Mier","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Heidelberg University Hospital  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8616-5599","authenticated-orcid":false,"given":"Philipp","family":"Uhl","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Institute of Pharmacy and Molecular Biotechnology Heidelberg University  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.4161\/viru.21282"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2014.956092"},{"key":"e_1_2_9_2_1","unstructured":"C. J.Kristich L. B.Rice C. A.Arias in Enterococci; From Commensals to Leading Causes of Drug Resistant Infection (Eds.:M. S.Gilmore D. B.Clewell Y.Ike N.Shankar) Massachusetts Eye and Ear Infirmary Boston2014."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy064"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2022.10.017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.52.070183.004141"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112829"},{"key":"e_1_2_9_8_1","first-page":"2","volume":"79","author":"Neu H. C.","year":"1985","journal-title":"Am. J. Med."},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2009.02563.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.9.1980"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01963633"},{"key":"e_1_2_9_9_3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.006052"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02273-19"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00199-11"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp503"},{"key":"e_1_2_9_12_2","first-page":"631","volume":"33","author":"Kisgen J.","year":"2008","journal-title":"P T"},{"key":"e_1_2_9_12_3","doi-asserted-by":"publisher","DOI":"10.2165\/00128071-200809040-00004"},{"key":"e_1_2_9_12_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112312"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-020-0710-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020617"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028020929988"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pep2.24059"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.2c00406"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202002727"},{"key":"e_1_2_9_18_1","unstructured":"EUCAST EUCAST System for Antimicrobial Abbreviations2018."},{"key":"e_1_2_9_19_1","unstructured":"EUCAST Breakpoint tables for interpretation of MICs and zone diameters. In Version 14.02024."},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00115-20"},{"key":"e_1_2_9_21_1","unstructured":"CLSI Performance Standards for Antimicrobial Susceptibility Testing \u2013 M100. In 30th Edition2020."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1198-743x.2001.00295.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp405418y"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2017.06.002"},{"key":"e_1_2_9_25_1","first-page":"179","volume":"51","author":"Gagetti P.","year":"2019","journal-title":"Rev. Argent. Microbiol."},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw231"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.5.1125"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c01213"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.4.776"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.4.824"},{"key":"e_1_2_9_29_3","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.1.92"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11070889"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mex.2021.101543"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24162968"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01152-07"},{"key":"e_1_2_9_34_1","volume":"62","author":"Jones A. K.","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(02)00192-4"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202411406","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202411406","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202411406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T14:24:22Z","timestamp":1781274262000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202411406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,5]]},"references-count":45,"journal-issue":{"issue":"48","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/advs.202411406"],"URL":"https:\/\/doi.org\/10.1002\/advs.202411406","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,5]]},"assertion":[{"value":"2024-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2411406"}}