{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:12:56Z","timestamp":1792883576850,"version":"4.5.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Candida albicans<\/jats:italic>, a common commensal and opportunistic fungal pathogen in humans, can occasionally progress to disseminated candidiasis which is a serious condition with a high morbidity and fatality rate. The emergence of drug-resistant fungal strains compels us to look for an efficient treatment solution. Our earlier studies have demonstrated that the unique antimicrobial peptide AMP-17 from <jats:italic>Musca domestica<\/jats:italic> has a strong antifungal impact on <jats:italic>C. albicans in vitro<\/jats:italic>. Here, we verified the therapeutic effects of AMP-17 on systemic candidiasis <jats:italic>in vivo<\/jats:italic> and the peptide interacts with fluconazole, a common antifungal medication, to treat systemic candidiasis. In the disseminated candidiasis model of <jats:italic>Galleria mellonella<\/jats:italic> and mice challenged with <jats:italic>C. albicans<\/jats:italic>, AMP-17 increased the survival rates of infected larvae and mice to 66.7 and 75%, respectively. Furthermore, the peptide lowered the load of <jats:italic>C. albicans<\/jats:italic> in the infected larvae and the kidneys of the mice by nearly 90%. Additional histological examination and measurements of plasma cytokines showed that the injection of AMP-17 markedly reduced the inflammatory response and balanced cytokine expression. Furthermore, checkerboard micro dilution experiments demonstrated that AMP-17 and fluconazole worked in synergy to inhibit <jats:italic>C. albicans<\/jats:italic> in the biofilm mode. According to morphological studies, AMP-17 and fluconazole together decreased the production of hyphae throughout the <jats:italic>C. albicans<\/jats:italic> biofilm formation process, loosening the mature biofilms\u2019 structure and lowering the amount of carbohydrates in the extracellular matrix (ECM) of the biofilms. Taken together, these results showed that AMP-17 would be a viable treatment for systemic candidiasis and might be a different approach to combating <jats:italic>Candida<\/jats:italic> biofilm, either by itself or in conjunction with fluconazole.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1480808","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T06:10:56Z","timestamp":1730441456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Antimicrobial peptide AMP-17 induces protection against systemic candidiasis and interacts synergistically with fluconazole against Candida albicans biofilm"],"prefix":"10.3389","volume":"15","author":[{"given":"Chaoqin","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longbing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuqing","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlong","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1131416","DOI":"10.3389\/fcimb.2023.1131416","article-title":"Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi","volume":"13","author":"An","year":"2023","journal-title":"Front. 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Microbiol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"102775","DOI":"10.1016\/j.ebiom.2020.102775","article-title":"Antimicrobial and antibiofilm activity of the EeCentrocin 1 derived peptide EC1-17KV via membrane disruption","volume":"55","author":"Ma","year":"2020","journal-title":"EBioMedicine"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.2147\/idr.S250278","article-title":"Antimicrobial peptide AMP-17 affects Candida albicans by disrupting its cell wall and cell membrane integrity","volume":"13","author":"Ma","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1021\/acsinfecdis.2c00080","article-title":"Tachyplesin I analogue peptide as an effective antimicrobial agent against Candida albicans-Staphylococcus aureus poly-biofilm formation and mixed infection","volume":"8","author":"Miao","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s11908-005-0044-7","article-title":"Global trends in candidemia: review of reports from 1995-2005","volume":"7","author":"Morgan","year":"2005","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1080\/08927014.2020.1776856","article-title":"Aluminium oxide nanoparticles inhibit EPS production, adhesion and biofilm formation by multidrug resistant Acinetobacter baumannii","volume":"36","author":"Muzammil","year":"2020","journal-title":"Biofouling"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"5973","DOI":"10.3390\/ijms21175973","article-title":"Therapeutic potential of cathelicidin peptide LL-37, an antimicrobial agent, in a murine sepsis model","volume":"21","author":"Nagaoka","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-micro-091014-104330","article-title":"Candida albicans biofilms and human disease","volume":"69","author":"Nobile","year":"2015","journal-title":"Ann. Rev. Microbiol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis","volume":"4","author":"Pappas","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"110550","DOI":"10.1016\/j.biopha.2020.110550","article-title":"Immune defence to invasive fungal infections: a comprehensive review","volume":"130","author":"Pathakumari","year":"2020","journal-title":"Biomed. 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NIAID mycoses study group and the Candidemia study group","volume":"39","author":"Rex","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"11578","DOI":"10.1039\/d1cc03793e","article-title":"Advances on chemically modified antimicrobial peptides for generating peptide antibiotics","volume":"57","author":"Rezende","year":"2021","journal-title":"Chem. Commun."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.3390\/antibiotics11111474","article-title":"The antimicrobial peptide AMP-17 derived from Musca domestica inhibits biofilm formation and eradicates mature biofilm in Candida albicans","volume":"11","author":"Sun","year":"2022","journal-title":"Antibiotics"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e3001762","DOI":"10.1371\/journal.pbio.3001762","article-title":"Niclosamide-loaded nanoparticles disrupt Candida biofilms and protect mice from mucosal candidiasis","volume":"20","author":"Sutar","year":"2022","journal-title":"PLoS Biol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"3715","DOI":"10.2147\/ijn.S93105","article-title":"Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?","volume":"11","author":"Voltan","year":"2016","journal-title":"Int. J. Nanomedicine"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"992275","DOI":"10.3389\/fmicb.2022.992275","article-title":"The prophylactic effects of monoclonal antibodies targeting the cell wall Pmt4 protein epitopes of Candida albicans in a murine model of invasive candidiasis","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"3318","DOI":"10.1128\/aac.05995-11","article-title":"Membrane-active action mode of polybia-CP, a novel antimicrobial peptide isolated from the venom of Polybia Paulista","volume":"56","author":"Wang","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.3389\/fmicb.2016.02173","article-title":"Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species","volume":"7","author":"Whaley","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1086\/421946","article-title":"Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study","volume":"39","author":"Wisplinghoff","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.ijantimicag.2013.09.005","article-title":"Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities","volume":"43","author":"Wisplinghoff","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"104385","DOI":"10.1016\/j.jprot.2021.104385","article-title":"TMT-based quantitative proteomic analysis of the effects of novel antimicrobial peptide AMP-17 against Candida albicans","volume":"250","author":"Yang","year":"2022","journal-title":"J. Proteome"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"304","DOI":"10.13345\/j.cjb.220499","article-title":"Identification of the target site of antimicrobial peptide AMP-17 against Candida albicans","volume":"39","author":"Yang","year":"2023","journal-title":"Sheng Wu Gong Cheng Xue Bao"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"233","DOI":"10.2147\/idr.S344246","article-title":"In vitro antifungal activity of a novel antimicrobial peptide AMP-17 against planktonic cells and biofilms of Cryptococcus neoformans","volume":"15","author":"Yang","year":"2022","journal-title":"Infect. 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