{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:22:03Z","timestamp":1789474923869,"version":"build-2803163510"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012483","name":"University of Georgia Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012483","name":"University of Georgia Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012483","name":"University of Georgia Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI144498"],"award-info":[{"award-number":["R21AI144498"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI144498"],"award-info":[{"award-number":["R21AI144498"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI148890"],"award-info":[{"award-number":["R21AI148890"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI148890"],"award-info":[{"award-number":["R21AI148890"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI150641"],"award-info":[{"award-number":["R21AI150641"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008065","name":"Georgia Research Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Globally, there are several million individuals with life-threatening invasive fungal diseases such as candidiasis, aspergillosis, cryptococcosis, <jats:italic>Pneumocystis<\/jats:italic> pneumonia (PCP), and mucormycosis. The mortality rate for these diseases generally exceeds 40%. Annual medical costs to treat these invasive fungal diseases in the United States exceed several billion dollars. In addition to AIDS patients, the risks of invasive mycoses are increasingly found in immune-impaired individuals or in immunosuppressed patients following stem cell or organ transplant or implantation of medical devices. Current antifungal drug therapies are not meeting the challenge, because (1) at safe doses, they do not provide sufficient fungal clearance to prevent reemergence of infection; (2) most become toxic with extended use; (3) drug-resistant fungal isolates are emerging; and (4) only one new class of antifungal drugs has been approved for clinical use in the last 2 decades. DectiSomes represent a novel design of drug delivery to drastically increase drug efficacy. Antifungals packaged in liposomes are targeted specifically to where the pathogen is, through binding to the fungal cell walls or exopolysaccharide matrices using the carbohydrate recognition domains of pathogen receptors. Relative to untargeted liposomal drug, DectiSomes show order of magnitude increases in the binding to and killing of <jats:italic>Candida albicans<\/jats:italic>, <jats:italic>Cryptococcus neoformans<\/jats:italic>, and <jats:italic>Aspergillus fumigatus<\/jats:italic> in vitro and similarly improved efficacy in mouse models of pulmonary aspergillosis. DectiSomes have the potential to usher in a new antifungal drug treatment paradigm.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009699","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T17:24:45Z","timestamp":1626974685000},"page":"e1009699","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Aiming for a bull\u2019s-eye: Targeting antifungals to fungi with dectin-decorated liposomes"],"prefix":"10.1371","volume":"17","author":[{"given":"Richard B.","family":"Meagher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary A.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4658-0245","authenticated-orcid":true,"given":"Suresh","family":"Ambati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3390-8387","authenticated-orcid":true,"given":"Xiaorong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"issue":"1","key":"ppat.1009699.ref001","article-title":"Global Epidemiology of Mucormycosis","volume":"5","author":"H Prakash","year":"2019","journal-title":"J Fungi (Basel)."},{"issue":"4","key":"ppat.1009699.ref002","first-page":"1","article-title":"Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision","volume":"3","author":"F Bongomin","year":"2017","journal-title":"J Fungi (Basel)."},{"issue":"11","key":"ppat.1009699.ref003","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1093\/cid\/ciy776","article-title":"Estimation of Direct Healthcare Costs of Fungal Diseases in the United States","volume":"68","author":"K Benedict","year":"2019","journal-title":"Clin Infect Dis"},{"issue":"3","key":"ppat.1009699.ref004","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.tim.2014.01.001","article-title":"A neglected epidemic: fungal infections in HIV\/AIDS","volume":"22","author":"D Armstrong-James","year":"2014","journal-title":"Trends Microbiol"},{"key":"ppat.1009699.ref005","article-title":"Antifungal susceptibility does not correlate with fungal clearance or survival in AIDS-associated cryptococcal meningitis","author":"L O\u2019Connor","year":"2020","journal-title":"Clin Infect Dis"},{"issue":"Suppl_6)","key":"ppat.1009699.ref006","doi-asserted-by":"crossref","first-page":"S678","DOI":"10.1093\/cid\/civ819","article-title":"The Regulatory Pathway for Antifungal Drugs: A US Perspective","volume":"61","author":"J Tillotson","year":"2015","journal-title":"Clin Infect Dis"},{"key":"ppat.1009699.ref007","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pharmthera.2018.10.008","article-title":"Antifungal drugs: New insights in research & development","volume":"195","author":"A Nicola","year":"2019","journal-title":"Pharmacol Ther"},{"issue":"12","key":"ppat.1009699.ref008","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/s41429-018-0100-9","article-title":"Potential targets for the development of new antifungal drugs","volume":"71","author":"H Su","year":"2018","journal-title":"J Antibiot"},{"issue":"5","key":"ppat.1009699.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mSphere.00715-19","article-title":"Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy.","volume":"4","author":"S Ambati","year":"2019","journal-title":"mSphere"},{"key":"ppat.1009699.ref010","first-page":"1","article-title":"Dectin-1-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy","volume":"4","author":"S Ambati","year":"2019","journal-title":"mSphere"},{"issue":"1","key":"ppat.1009699.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.00030-21","article-title":"Antifungal Liposomes Directed by Dectin-2 Offer a Promising Therapeutic Option for Pulmonary Aspergillosis.","volume":"12","author":"S Ambati","year":"2021","journal-title":"mBio."},{"key":"ppat.1009699.ref012","author":"inventors; University of Georgia Research Foundation, Inc. (Athens, GA, US), assignee","year":"2019","journal-title":"Targeted Nanoparticles and Their Uses Related to Fungal Infections"},{"key":"ppat.1009699.ref013","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3389\/fimmu.2018.01261","article-title":"Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors","volume":"9","author":"S Goyal","year":"2018","journal-title":"TheFront Immunol"},{"key":"ppat.1009699.ref014","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jconrel.2018.02.015","article-title":"Immunoliposomes in clinical oncology: State of the art and future perspectives","volume":"275","author":"M Merino","year":"2018","journal-title":"J Control Release"},{"key":"ppat.1009699.ref015","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.colsurfb.2017.07.085","article-title":"Immunoliposomes: A review on functionalization strategies and targets for drug delivery","volume":"159","author":"J Eloy","year":"2017","journal-title":"Colloids Surf B Biointerfaces"},{"key":"ppat.1009699.ref016","first-page":"439","volume-title":"3.2 Galactomannan (GM) Immunoassay for Acute Aspergillosis","author":"T Lion","year":"2017"},{"issue":"Pt 10","key":"ppat.1009699.ref017","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1099\/mic.0.27318-0","article-title":"The Aspergillus fumigatus cell wall is organized in domains that are remodelled during polarity establishment","volume":"150","author":"M Momany","year":"2004","journal-title":"Microbiology"},{"issue":"6","key":"ppat.1009699.ref018","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.4049\/jimmunol.176.6.3717","article-title":"Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states","volume":"176","author":"G Gersuk","year":"2006","journal-title":"J Immunol"},{"issue":"4","key":"ppat.1009699.ref019","doi-asserted-by":"crossref","first-page":"e42","DOI":"10.1371\/journal.ppat.0010042","article-title":"The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus","volume":"1","author":"C Steele","year":"2005","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1009699.ref020","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1124\/jpet.107.133124","article-title":"Differential high-affinity interaction of dectin-1 with natural or synthetic glucans is dependent upon primary structure and is influenced by polymer chain length and side-chain branching","volume":"325","author":"E Adams","year":"2008","journal-title":"J Pharmacol Exp Ther"},{"issue":"32","key":"ppat.1009699.ref021","doi-asserted-by":"crossref","first-page":"13402","DOI":"10.1074\/jbc.M117.799080","article-title":"Mechanism of pathogen recognition by human Dectin-2","volume":"292","author":"H Feinberg","year":"2017","journal-title":"J Biol Chem"},{"issue":"5","key":"ppat.1009699.ref022","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/glycob\/cwj077","article-title":"The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose","volume":"16","author":"P McGreal","year":"2006","journal-title":"Glycobiology"},{"issue":"2","key":"ppat.1009699.ref023","first-page":"109","article-title":"Pricing of monoclonal antibody therapies: higher if used for cancer?","volume":"24","author":"I Hernandez","year":"2018","journal-title":"Am J Manag Care"},{"issue":"7","key":"ppat.1009699.ref024","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1128\/AAC.49.7.2851-2856.2005","article-title":"Cryptococcus neoformans resistance to echinocandins: (1,3)beta-glucan synthase activity is sensitive to echinocandins","volume":"49","author":"M Maligie","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"ppat.1009699.ref025","volume-title":"Essentials of Glycobiology","author":"R Cummings","year":"2017","edition":"3"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009699","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T17:25:05Z","timestamp":1626974705000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009699"}},"subtitle":[],"editor":[{"given":"Mary Ann","family":"Jabra-Rizk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":25,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009699","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]}}}