{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T20:19:42Z","timestamp":1771013982701,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013954","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000}}],"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Municipal Science and Technology Major Project","award":["ZD2021CY001"],"award-info":[{"award-number":["ZD2021CY001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030062"],"award-info":[{"award-number":["82030062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202529"],"award-info":[{"award-number":["82202529"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M690666"],"award-info":[{"award-number":["2021M690666"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022T150129"],"award-info":[{"award-number":["2022T150129"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Harnessing antimicrobial peptides as bactericidal agents affords an attractive approach to developing new anti-infective therapies. We found that abolishing disulfide bonding in mouse cryptdin 1 (Crp1), a weakly bactericidal \u03b1-defensin of 35 residues, turned it into a potent antimicrobial peptide against Gram-negative bacteria. Here we report that Crp1 in its natively folded \u03b2-sheet structure forms high-ordered nanonets to cloak, but not kill,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , whereas its disulfide-devoid linear counterpart (L-Crp1) readily disintegrates the bacterial membrane as monomers. L-Crp1 adopts a helix-loop-helix conformation in molecular dynamics simulations, likely conducive to productive peptide-membrane interactions detrimental to bacteria. A truncated peptide spanning the helix-loop-helix, L-Crp1\n                    <jats:sup>1-25<\/jats:sup>\n                    , maintains the same conformation as and similar membranolytic and bactericidal activities to L-Crp1. Remarkably, intraperitoneally administered L-Crp1\n                    <jats:sup>1-25<\/jats:sup>\n                    rescues\n                    <jats:italic>E. coli<\/jats:italic>\n                    -challenged mice from lethality in a sepsis model by effectively reducing bacterial burden, inflammation and tissue damage. Our studies cultivate additional mechanistic insights into the mode of action of defensins and shed new light on how to harness these host factors for potential therapeutic use.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013954","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T18:45:01Z","timestamp":1770662701000},"page":"e1013954","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breaking disulfide bonds in a weakly bactericidal \u03b1-defensin unleashes a potent antimicrobial peptide with an altered conformation"],"prefix":"10.1371","volume":"22","author":[{"given":"Gan","family":"Luo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingzhu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongbing","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1318-9968","authenticated-orcid":true,"given":"Wuyuan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"issue":"5820","key":"ppat.1013954.ref001","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/292246a0","article-title":"Sequence and specificity of two antibacterial proteins involved in insect immunity","volume":"292","author":"H Steiner","year":"1981","journal-title":"Nature"},{"issue":"6870","key":"ppat.1013954.ref002","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/415389a","article-title":"Antimicrobial peptides of multicellular organisms","volume":"415","author":"M Zasloff","year":"2002","journal-title":"Nature"},{"issue":"9","key":"ppat.1013954.ref003","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/nri1180","article-title":"Defensins: antimicrobial peptides of innate immunity","volume":"3","author":"T Ganz","year":"2003","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"ppat.1013954.ref004","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/ni1206","article-title":"Mammalian defensins in the antimicrobial immune response","volume":"6","author":"ME Selsted","year":"2005","journal-title":"Nat Immunol"},{"issue":"1","key":"ppat.1013954.ref005","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/j.1600-065X.2011.01082.x","article-title":"\u03b1-Defensins in human innate immunity","volume":"245","author":"RI Lehrer","year":"2012","journal-title":"Immunol Rev"},{"issue":"1","key":"ppat.1013954.ref006","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/iai.42.1.10-14.1983","article-title":"Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages","volume":"42","author":"RI Lehrer","year":"1983","journal-title":"Infect Immun"},{"issue":"23","key":"ppat.1013954.ref007","doi-asserted-by":"crossref","first-page":"14485","DOI":"10.1016\/S0021-9258(17)43888-9","article-title":"Primary structures of MCP-1 and MCP-2, natural peptide antibiotics of rabbit lung macrophages.","volume":"258","author":"ME Selsted","year":"1983","journal-title":"Journal of Biological Chemistry"},{"issue":"4","key":"ppat.1013954.ref008","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1172\/JCI112120","article-title":"Defensins. 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