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Thus, there is an urgent need for new therapeutic approaches to candidiasis, including strategies bioinspired by insights into natural host defense against fungal pathogens. The antifungal properties of \u03b8-defensins, macrocyclic peptides expressed in tissues of Old World monkeys, were investigated against a panel of drug-sensitive and drug-resistant clinical isolates of\n            <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n            and non-\n            <jats:named-content content-type=\"genus-species\">albicans Candida<\/jats:named-content>\n            species. Rhesus \u03b8-defensin 1 (RTD-1), the prototype \u03b8-defensin, was rapidly and potently fungicidal against drug-sensitive and MDR\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            strains. Fungal killing occurred by cell permeabilization that was temporally correlated with ATP release and intracellular accumulation of reactive oxygen species (ROS). Killing by RTD-1 was compared with that by histatin 5 (Hst 5), an extensively characterized anticandidal peptide expressed in human saliva. RTD-1 killed\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            much more rapidly and at a &gt;200-fold lower concentration than that of Hst 5. Unlike Hst 5, the anticandidal activity of RTD-1 was independent of mitochondrial ATP production. Moreover, RTD-1 was completely resistant to\n            <jats:named-content content-type=\"genus-species\">Candida<\/jats:named-content>\n            proteases for 2 h under conditions that rapidly and completely degraded Hst 5. MICs and minimum fungicidal concentrations (MFCs) of 14 natural \u03b8-defensins isoforms against drug-resistant\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            isolates identified peptides that are more active than amphotericin B and\/or caspofungin against fluconazole-resistant organisms, including MDR\n            <jats:named-content content-type=\"genus-species\">Candida auris.<\/jats:named-content>\n            These results point to the potential of macrocyclic \u03b8-defensins as structural templates for the design of antifungal therapeutics.\n          <\/jats:p>","DOI":"10.1128\/aac.00111-18","type":"journal-article","created":{"date-parts":[[2018,3,29]],"date-time":"2018-03-29T13:26:12Z","timestamp":1522329972000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Fungicidal Potency and Mechanisms of \u03b8-Defensins against Multidrug-Resistant Candida Species"],"prefix":"10.1128","volume":"62","author":[{"given":"Virginia","family":"Basso","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dat Q.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"},{"name":"Oryn Therapeutics, Vacaville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0069-4917","authenticated-orcid":false,"given":"Justin B.","family":"Schaal","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patti","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ngole","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younus","family":"Aqeel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasad","family":"Tongaonkar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 J.","family":"Ouellette","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"},{"name":"Norris Comprehensive Cancer Center of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7152-4739","authenticated-orcid":false,"given":"Michael E.","family":"Selsted","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"},{"name":"Norris Comprehensive Cancer Center of the University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1315399"},{"key":"e_1_3_3_3_2","first-page":"183","article-title":"Epidemiology of opportunistic invasive mycoses","volume":"7","author":"Kullberg BJ","year":"2002","unstructured":"Kullberg BJ, Oude Lashof AM. 2002. 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