{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:24Z","timestamp":1792787604056,"version":"4.5.0"},"reference-count":76,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":55,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["P01AI083214,P20GM121344"],"award-info":[{"award-number":["P01AI083214,P20GM121344"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,16]]},"abstract":"<jats:p>\n                    As antimicrobial resistance rises, new antibacterial candidates are urgently needed. Using sequence space information from over 14,743 functional antimicrobial peptides (AMPs), we improved the antimicrobial properties of citropin 1.1, an AMP with weak antimethicillin resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA) activity, producing a short and potent antistaphylococcal peptide, CIT-8 (13 residues). At 40 \u03bcg\/mL, CIT-8 eradicated 1 \u00d7 10\n                    <jats:sup>8<\/jats:sup>\n                    drug-resistant MRSA and vancomycin resistant\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    (VRSA) persister cells within 30 minutes of exposure and reduced the number of viable biofilm cells of MRSA and VRSA by 3 log\n                    <jats:sub>10<\/jats:sub>\n                    and 4 log\n                    <jats:sub>10<\/jats:sub>\n                    in established biofilms, respectively. CIT-8 (at 32 \u03bcg\/mL) depolarized and permeated the\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>aureus<\/jats:italic>\n                    MW2 membrane. In a mouse model of MRSA skin infection, CIT-8 (2% w\/w in petroleum jelly) significantly reduced the bacterial burden by 2.3 log\n                    <jats:sub>10<\/jats:sub>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Our methodology accelerated AMP design by combining traditional peptide design strategies, such as truncation, substitution, and structure-guided alteration, with machine learning\u2013backed sequence optimization.\n                  <\/jats:p>","DOI":"10.1172\/jci185430","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T12:00:16Z","timestamp":1745323216000},"source":"Crossref","is-referenced-by-count":26,"title":["Antimicrobial peptide developed with machine learning sequence optimization targets drug resistant Staphylococcus aureus in mice"],"prefix":"10.1172","volume":"135","author":[{"given":"Biswajit","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindya","family":"Basu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, and"},{"name":"School of Biomolecular Engineering & Biotechnology, Rajiv Gandhi Technological University, Gandhinagar, Bhopal, Madhya Pradesh, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Shehadeh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA."},{"name":"Department of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LewisOscar","family":"Felix","sequence":"additional","affiliation":[{"name":"Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Sundeep","family":"Kollala","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashpal Singh","family":"Chhonker","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandar T.","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology & Biochemistry, Brown University, Providence, Rhode Island, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charilaos","family":"Dellis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narchonai","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl J.","family":"Murry","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Gu","sequence":"additional","affiliation":[{"name":"Electron Microscopy Core, Houston Methodist Academic Institute, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Sealy Center for structural Biology and Molecular Biophysics, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick M.","family":"Ausubel","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul P.","family":"Sotiriadis","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece."},{"name":"Archimedes - Athena Research Center, Marousi, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftherios","family":"Mylonakis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1179\/2047773215Y.0000000030"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2017.03.014"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00037-22"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-010220-095711"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02351-15"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.22037\/ijpr.2019.112397.13734"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/ph13100271"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041470"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1021\/ja0584875"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/bip.22281"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112874"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1021\/ja305644e"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/psc.908"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan4044"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1021\/cb500475y"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature05233"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s10462-021-10058-4"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2018.01.005"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-022-00991-2"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1039\/D1SC01713F"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01226-0"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.05.013"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2024.09.008"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.02.016"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-001-0058-5"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00750.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1904700116"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s10540-006-9030-z"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/bi500779g"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00537-12"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821410116"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/cells7070084"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare11131946"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2009.07.012"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01089.x"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.7b01222"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics8040238"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043134"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.0c01441"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42434-9"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12040725"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbad240"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2005540117"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm692"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3390\/ph14050471"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003212"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2020.02.005"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.4.999-1007.2001"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2019.170119"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202306112"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-08247-4"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11081085"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.1c00101"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25003"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10010036"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507893112"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77554-X"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1021\/bi036153r"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1098"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/1758-2229.12936"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M115.054999"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525206113"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-015-0069-7"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2014.0557"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03001-15"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/srep29707"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4102"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1278"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa991"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1080"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1109\/ACCESS.2024.3350791"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1109\/TIT.1982.1056489"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/0377-0427(87)90125-7"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.artmed.2017.07.002"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/185430\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:57:23Z","timestamp":1779213443000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/185430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":76,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,4,15]]},"published-print":{"date-parts":[[2025,6,16]]}},"alternative-id":["10.1172\/JCI185430"],"URL":"https:\/\/doi.org\/10.1172\/jci185430","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,22]]},"article-number":"e185430"}}