{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:33:36Z","timestamp":1793903616411,"version":"4.8.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"publisher","award":["16-CSP-UNINA-007"],"award-info":[{"award-number":["16-CSP-UNINA-007"]}],"id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"publisher","award":["16-CSP-UNINA-007"],"award-info":[{"award-number":["16-CSP-UNINA-007"]}],"id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Candida<\/jats:italic> species cause cutaneous and systemic infections with a high mortality rate, especially in immunocompromised patients. The emergence of resistance to the most common antifungal drugs, also due to biofilm formation, requires the development of alternative antifungal agents. The antimicrobial peptide VLL-28, isolated from an archaeal transcription factor, shows comparable antifungal activity against 10 clinical isolates of <jats:italic>Candida<\/jats:italic> spp. Using a fluoresceinated derivative of this peptide, we found that VLL-28 binds to the surface of planktonic cells. This observation suggested that it could exert its antifungal activity by damaging the cell wall. In addition, analyses performed on biofilms via confocal microscopy revealed that VLL-28 is differentially active on all the strains tested, with <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> and <jats:italic>C<\/jats:italic>. <jats:italic>parapsilosis<\/jats:italic> being the most sensitive ones. Notably, VLL-28 is the first example of an archaeal antimicrobial peptide that is active towards <jats:italic>Candida<\/jats:italic> spp. Thus, this points to archaeal microorganisms as a possible reservoir of novel antifungal agents.<\/jats:p>","DOI":"10.1038\/s41598-018-35530-0","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T08:22:33Z","timestamp":1543393353000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Antifungal and anti-biofilm activity of the first cryptic antimicrobial peptide from an archaeal protein against Candida spp. clinical isolates"],"prefix":"10.1038","volume":"8","author":[{"given":"Emanuela","family":"Roscetto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Contursi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Vollaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2928-3609","authenticated-orcid":false,"given":"Salvatore","family":"Fusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Notomista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Catania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"35530_CR1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/S0966-842X(01)02094-7","volume":"9","author":"RA Calderone","year":"2001","unstructured":"Calderone, R. A. & Fonzi, W. A. Virulence factors of Candida albicans. Trends in microbiology 9, 327\u2013335 (2001).","journal-title":"Trends in microbiology"},{"key":"35530_CR2","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1086\/380796","volume":"38","author":"PG Pappas","year":"2004","unstructured":"Pappas, P. G. et al. Guidelines for treatment of candidiasis. Clinical Infectious Diseases 38, 161\u2013189 (2004).","journal-title":"Clinical Infectious Diseases"},{"key":"35530_CR3","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1093\/clinids\/20.6.1531","volume":"20","author":"RP Wenzel","year":"1995","unstructured":"Wenzel, R. P. Nosocomial candidemia: risk factors and attributable mortality. Clinical Infectious Diseases 20, 1531\u20131534 (1995).","journal-title":"Clinical Infectious Diseases"},{"key":"35530_CR4","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1086\/421946","volume":"39","author":"H Wisplinghoff","year":"2004","unstructured":"Wisplinghoff, H. et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clinical infectious diseases 39, 309\u2013317 (2004).","journal-title":"Clinical infectious diseases"},{"key":"35530_CR5","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.micpath.2018.02.028","volume":"117","author":"Maryam Dadar","year":"2018","unstructured":"Dadar, M. et al. Candida albicans-Biology, molecular characterization, pathogenicity, and advances in diagnosis and control\u2013An update. Microbial pathogenesis (2018).","journal-title":"Microbial Pathogenesis"},{"key":"35530_CR6","doi-asserted-by":"crossref","unstructured":"Vandecandelaere, I. & Coenye, T. In Biofilm-Based Healthcare-Associated Infections 137\u2013155 (Springer, 2015).","DOI":"10.1007\/978-3-319-11038-7_9"},{"key":"35530_CR7","doi-asserted-by":"crossref","unstructured":"Williams, C. & Ramage, G. In Biofilm-based healthcare-associated infections 11\u201327 (Springer, 2015).","DOI":"10.1007\/978-3-319-09782-4_2"},{"key":"35530_CR8","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1128\/CMR.17.2.255-267.2004","volume":"17","author":"EM Kojic","year":"2004","unstructured":"Kojic, E. M. & Darouiche, R. O. Candida infections of medical devices. Clinical microbiology reviews 17, 255\u2013267 (2004).","journal-title":"Clinical microbiology reviews"},{"key":"35530_CR9","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1128\/JCM.00131-07","volume":"45","author":"M Tumbarello","year":"2007","unstructured":"Tumbarello, M. et al. Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. Journal of clinical microbiology 45, 1843\u20131850 (2007).","journal-title":"Journal of clinical microbiology"},{"key":"35530_CR10","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s15010-013-0432-0","volume":"41","author":"M Montagna","year":"2013","unstructured":"Montagna, M. et al. Epidemiology of invasive fungal infections in the intensive care unit: results of a multicenter Italian survey (AURORA Project). Infection 41, 645\u2013653 (2013).","journal-title":"Infection"},{"key":"35530_CR11","doi-asserted-by":"publisher","first-page":"e99103","DOI":"10.1371\/journal.pone.0099103","volume":"9","author":"H-J Tang","year":"2014","unstructured":"Tang, H.-J., Liu, W.-L., Lin, H.-L. & Lai, C.-C. Epidemiology and prognostic factors of candidemia in cancer patients. PLoS One 9, e99103 (2014).","journal-title":"PLoS One"},{"key":"35530_CR12","doi-asserted-by":"publisher","first-page":"e101510","DOI":"10.1371\/journal.pone.0101510","volume":"9","author":"MA Pfaller","year":"2014","unstructured":"Pfaller, M. A. et al. Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004\u20132008. PLoS One 9, e101510 (2014).","journal-title":"PLoS One"},{"key":"35530_CR13","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.tim.2011.02.003","volume":"19","author":"S Silva","year":"2011","unstructured":"Silva, S. et al. Adherence and biofilm formation of non-Candida albicans Candida species. Trends in microbiology 19, 241\u2013247 (2011).","journal-title":"Trends in microbiology"},{"key":"35530_CR14","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/j.1574-6976.2011.00278.x","volume":"36","author":"S Silva","year":"2012","unstructured":"Silva, S. et al. Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. FEMS microbiology reviews 36, 288\u2013305 (2012).","journal-title":"FEMS microbiology reviews"},{"key":"35530_CR15","first-page":"7","volume":"13","author":"R Kolter","year":"2010","unstructured":"Kolter, R. Biofilms in lab and nature: a molecular geneticist\u2019s voyage to microbial ecology. Int Microbiol 13, 7 (2010).","journal-title":"Int Microbiol"},{"key":"35530_CR16","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/441300a","volume":"441","author":"R Kolter","year":"2006","unstructured":"Kolter, R. & Greenberg, E. P. Microbial sciences: the superficial life of microbes. Nature 441, 300 (2006).","journal-title":"Nature"},{"issue":"7","key":"35530_CR17","doi-asserted-by":"publisher","first-page":"a000398","DOI":"10.1101\/cshperspect.a000398","volume":"2","author":"D. Lopez","year":"2010","unstructured":"L\u00f3pez, D., Vlamakis, H. & Kolter, R. \u201cBiofilms.\u201d Cold Spring Harbor perspectives in biology a000398 (2010).","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"35530_CR18","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1007\/s10096-015-2323-z","volume":"34","author":"I Olsen","year":"2015","unstructured":"Olsen, I. Biofilm-specific antibiotic tolerance and resistance. European Journal of Clinical Microbiology & Infectious Diseases 34, 877\u2013886 (2015).","journal-title":"European Journal of Clinical Microbiology & Infectious Diseases"},{"key":"35530_CR19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/S0966-842X(02)00002-1","volume":"11","author":"LJ Douglas","year":"2003","unstructured":"Douglas, L. J. Candida biofilms and their role in infection. Trends in microbiology 11, 30\u201336 (2003).","journal-title":"Trends in microbiology"},{"key":"35530_CR20","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1128\/AAC.01056-06","volume":"51","author":"J Nett","year":"2007","unstructured":"Nett, J. et al. Putative role of \u03b2-1, 3 glucans in Candida albicans biofilm resistance. Antimicrobial agents and chemotherapy 51, 510\u2013520 (2007).","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"35530_CR21","doi-asserted-by":"publisher","first-page":"3839","DOI":"10.1128\/AAC.00684-06","volume":"50","author":"MD LaFleur","year":"2006","unstructured":"LaFleur, M. D., Kumamoto, C. A. & Lewis, K. Candida albicans biofilms produce antifungal-tolerant persister cells. Antimicrobial agents and chemotherapy 50, 3839\u20133846 (2006).","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"35530_CR22","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1086\/651200","volume":"202","author":"JE Nett","year":"2010","unstructured":"Nett, J. E., Sanchez, H., Cain, M. T. & Andes, D. R. Genetic basis of Candida biofilm resistance due to drug-sequestering matrix glucan. The Journal of infectious diseases 202, 171\u2013175 (2010).","journal-title":"The Journal of infectious diseases"},{"key":"35530_CR23","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1128\/EC.4.4.633-638.2005","volume":"4","author":"G Ramage","year":"2005","unstructured":"Ramage, G., Saville, S. P., Thomas, D. P. & Lopez-Ribot, J. L. Candida biofilms: an update. Eukaryotic cell 4, 633\u2013638 (2005).","journal-title":"Eukaryotic cell"},{"key":"35530_CR24","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-micro-091014-104330","volume":"69","author":"CJ Nobile","year":"2015","unstructured":"Nobile, C. J. & Johnson, A. D. Candida albicans biofilms and human disease. Annual review of microbiology 69, 71\u201392 (2015).","journal-title":"Annual review of microbiology"},{"key":"35530_CR25","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.ajic.2011.01.003","volume":"39","author":"NP O\u2019grady","year":"2011","unstructured":"O\u2019grady, N. P. et al. Guidelines for the prevention of intravascular catheter-related infections. American journal of infection control 39, S1\u2013S34 (2011).","journal-title":"American journal of infection control"},{"key":"35530_CR26","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","volume":"62","author":"PG Pappas","year":"2015","unstructured":"Pappas, P. G. et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clinical Infectious Diseases 62, e1\u2013e50 (2015).","journal-title":"Clinical Infectious Diseases"},{"key":"35530_CR27","unstructured":"World Health Organization. Antimicrobial resistance: global report on surveillance (World Health Organization, 2014)."},{"key":"35530_CR28","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.amjmed.2011.11.001","volume":"125","author":"MA Pfaller","year":"2012","unstructured":"Pfaller, M. A. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. The American journal of medicine 125, S3\u2013S13 (2012).","journal-title":"The American journal of medicine"},{"key":"35530_CR29","doi-asserted-by":"crossref","unstructured":"Haney, E. F., Mansour, S. C. & Hancock, R. E. In Antimicrobial Peptides 3\u201322 (Springer, 2017).","DOI":"10.1007\/978-1-4939-6737-7_1"},{"key":"35530_CR30","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.it.2014.07.004","volume":"35","author":"SC Mansour","year":"2014","unstructured":"Mansour, S. C., Pena, O. M. & Hancock, R. E. Host defense peptides: front-line immunomodulators. Trends in immunology 35, 443\u2013450 (2014).","journal-title":"Trends in immunology"},{"key":"35530_CR31","doi-asserted-by":"crossref","unstructured":"Pizzo, E., Cafaro, V., Di, A. D. & Notomista, E. Cryptic Antimicrobial Peptides: identification methods and current knowledge of their immunomodulatory properties. Current pharmaceutical design (2018).","DOI":"10.2174\/1381612824666180327165012"},{"key":"35530_CR32","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.jtbi.2017.02.012","volume":"419","author":"K Pane","year":"2017","unstructured":"Pane, K. et al. Antimicrobial potency of cationic antimicrobial peptides can be predicted from their amino acid composition: Application to the detection of \u201ccryptic\u201d antimicrobial peptides. Journal of theoretical biology 419, 254\u2013265 (2017).","journal-title":"Journal of theoretical biology"},{"key":"35530_CR33","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1128\/EC.00093-14","volume":"13","author":"M Swidergall","year":"2014","unstructured":"Swidergall, M. & Ernst, J. F. Interplay between Candida albicans and the antimicrobial peptide armory. Eukaryotic cell 13, 950\u2013957 (2014).","journal-title":"Eukaryotic cell"},{"key":"35530_CR34","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.jmii.2016.12.005","volume":"50","author":"PY Chung","year":"2017","unstructured":"Chung, P. Y. & Khanum, R. Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria. Journal of Microbiology, Immunology and Infection 50, 405\u2013410 (2017).","journal-title":"Journal of Microbiology, Immunology and Infection"},{"key":"35530_CR35","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1016\/j.bbagen.2017.04.009","volume":"1861","author":"A Bosso","year":"2017","unstructured":"Bosso, A. et al. A new cryptic host defense peptide identified in human 11-hydroxysteroid dehydrogenase-1 \u03b2-like: from in silico identification to experimental evidence. Biochimica et Biophysica Acta (BBA)-General Subjects 1861, 2342\u20132353 (2017).","journal-title":"Biochimica et Biophysica Acta (BBA)-General Subjects"},{"key":"35530_CR36","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.bcp.2017.01.009","volume":"130","author":"R Gaglione","year":"2017","unstructured":"Gaglione, R. et al. Novel human bioactive peptides identified in Apolipoprotein B: Evaluation of their therapeutic potential. Biochemical pharmacology 130, 34\u201350 (2017).","journal-title":"Biochemical pharmacology"},{"key":"35530_CR37","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1128\/AAC.01670-13","volume":"58","author":"SR Ordonez","year":"2014","unstructured":"Ordonez, S. R., Amarullah, I. H., Wubbolts, R. W., Veldhuizen, E. J. & Haagsman, H. P. Fungicidal mechanisms of cathelicidins LL-37 and CATH-2 revealed by live-cell imaging. Antimicrobial agents and chemotherapy 58, 2240\u20132248 (2014).","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"35530_CR38","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1042\/BJ20042099","volume":"388","author":"AL Den Hertog","year":"2005","unstructured":"Den Hertog, A. L., Van Marle, J., Bolscher, J. G., Veerman, E. C. & Arie, V. Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane. Biochemical Journal 388, 689\u2013695 (2005).","journal-title":"Biochemical Journal"},{"key":"35530_CR39","doi-asserted-by":"publisher","first-page":"5993","DOI":"10.1093\/nar\/gku215","volume":"42","author":"P Contursi","year":"2014","unstructured":"Contursi, P. et al. Structural and functional studies of Stf76 from the Sulfolobus islandicus plasmid\u2013virus pSSVx: a novel peculiar member of the winged helix\u2013turn\u2013helix transcription factor family. Nucleic acids research 42, 5993\u20136011 (2014).","journal-title":"Nucleic acids research"},{"key":"35530_CR40","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s00792-014-0634-0","volume":"18","author":"P Contursi","year":"2014","unstructured":"Contursi, P., Fusco, S., Cannio, R. & She, Q. Molecular biology of fuselloviruses and their satellites. Extremophiles 18, 473\u2013489 (2014).","journal-title":"Extremophiles"},{"key":"35530_CR41","doi-asserted-by":"publisher","first-page":"6339","DOI":"10.1128\/JB.00638-07","volume":"189","author":"P Contursi","year":"2007","unstructured":"Contursi, P. et al. Transcriptional analysis of the genetic element pSSVx: differential and temporal regulation of gene expression reveals correlation between transcription and replication. Journal of bacteriology 189, 6339\u20136350 (2007).","journal-title":"Journal of bacteriology"},{"key":"35530_CR42","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00792-010-0325-4","volume":"14","author":"P Contursi","year":"2010","unstructured":"Contursi, P., Cannio, R. & She, Q. Transcription termination in the plasmid\/virus hybrid pSSVx from Sulfolobus islandicus. Extremophiles 14, 453\u2013463 (2010).","journal-title":"Extremophiles"},{"key":"35530_CR43","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s00792-013-0586-9","volume":"17","author":"P Contursi","year":"2013","unstructured":"Contursi, P., Fusco, S., Limauro, D. & Fiorentino, G. Host and viral transcriptional regulators in Sulfolobus: an overview. Extremophiles 17, 881\u2013895 (2013).","journal-title":"Extremophiles"},{"key":"35530_CR44","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1007\/s00792-014-0717-y","volume":"19","author":"S Fusco","year":"2015","unstructured":"Fusco, S., Aulitto, M., Bartolucci, S. & Contursi, P. A standardized protocol for the UV induction of Sulfolobus spindle-shaped virus 1. Extremophiles 19, 539\u2013546 (2015).","journal-title":"Extremophiles"},{"key":"35530_CR45","doi-asserted-by":"publisher","first-page":"6453","DOI":"10.1128\/JVI.00363-15","volume":"89","author":"S Fusco","year":"2015","unstructured":"Fusco, S., She, Q., Fiorentino, G., Bartolucci, S. & Contursi, P. Unravelling the role of the F55 regulator in the transition from lysogeny to UV induction of Sulfolobus spindle-shaped virus 1. Journal of virology 89, 6453\u20136461 (2015).","journal-title":"Journal of virology"},{"key":"35530_CR46","doi-asserted-by":"crossref","unstructured":"Prato, S., et al. Molecular modeling and functional characterization of the monomeric primase\u2013polymerase domain from the Sulfolobus solfataricus plasmid pIT3. 275(17), 4389\u20134402 (2008).","DOI":"10.1111\/j.1742-4658.2008.06585.x"},{"key":"35530_CR47","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-015-0302-9","volume":"14","author":"E Notomista","year":"2015","unstructured":"Notomista, E. et al. The identification of a novel Sulfolobus islandicus CAMP-like peptide points to archaeal microorganisms as cell factories for the production of antimicrobial molecules. Microbial cell factories 14, 126 (2015).","journal-title":"Microbial cell factories"},{"key":"35530_CR48","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1016\/j.bbagen.2017.06.009","volume":"1861","author":"R Gaglione","year":"2017","unstructured":"Gaglione, R. et al. Insights into the anticancer properties of the first antimicrobial peptide fromArchaea. Biochimica et Biophysica Acta (BBA)-General Subjects 1861, 2155\u20132164 (2017).","journal-title":"Biochimica et Biophysica Acta (BBA)-General Subjects"},{"key":"35530_CR49","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1042\/bj3560361","volume":"356","author":"A Ruissen","year":"2001","unstructured":"Ruissen, A. et al. Effects of histatin 5 and derived peptides on Candida albicans. Biochemical Journal 356, 361 (2001).","journal-title":"Biochemical Journal"},{"key":"35530_CR50","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1111\/febs.13725","volume":"283","author":"K Pane","year":"2016","unstructured":"Pane, K. et al. A new cryptic cationic antimicrobial peptide from human apolipoprotein E with antibacterial activity and immunomodulatory effects on human cells. The FEBS journal 283, 2115\u20132131 (2016).","journal-title":"The FEBS journal"},{"key":"35530_CR51","doi-asserted-by":"publisher","first-page":"256","DOI":"10.2174\/092986711794088399","volume":"18","author":"G Batoni","year":"2011","unstructured":"Batoni, G., Maisetta, G., Lisa Brancatisano, F., Esin, S. & Campa, M. Use of antimicrobial peptides against microbial biofilms: advantages and limits. Current medicinal chemistry 18, 256\u2013279 (2011).","journal-title":"Current medicinal chemistry"},{"key":"35530_CR52","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1128\/AAC.47.3.956-964.2003","volume":"47","author":"C Onyewu","year":"2003","unstructured":"Onyewu, C., Blankenship, J. R., Del Poeta, M. & Heitman, J. Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrobial agents and chemotherapy 47, 956\u2013964 (2003).","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"35530_CR53","doi-asserted-by":"publisher","first-page":"555","DOI":"10.2174\/1389557516666160118112103","volume":"16","author":"TK Mazu","year":"2016","unstructured":"Mazu, T. K., Bricker, B. A., Flores-Rozas, H. & Ablordeppey, S. Y. The Mechanistic Targets of Antifungal Agents: An Overview. Mini reviews in medicinal chemistry 16, 555\u2013578 (2016).","journal-title":"Mini reviews in medicinal chemistry"},{"key":"35530_CR54","doi-asserted-by":"publisher","first-page":"11","DOI":"10.2165\/11585270-000000000-00000","volume":"71","author":"SC-A Chen","year":"2011","unstructured":"Chen, S. C.-A., Slavin, M. A. & Sorrell, T. C. Echinocandin antifungal drugs in fungal infections. Drugs 71, 11\u201341 (2011).","journal-title":"Drugs"},{"key":"35530_CR55","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s12602-016-9212-3","volume":"8","author":"K Singh","year":"2016","unstructured":"Singh, K. & Rani, J. Sequential and Structural Aspects of Antifungal Peptides from Animals, Bacteria and Fungi Based on Bioinformatics Tools. Probiotics and antimicrobial proteins 8, 85\u2013101 (2016).","journal-title":"Probiotics and antimicrobial proteins"},{"key":"35530_CR56","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1128\/JCM.42.3.1024-1029.2004","volume":"42","author":"S Joly","year":"2004","unstructured":"Joly, S., Maze, C., McCray, P. B. & Guthmiller, J. M. Human \u03b2-defensins 2 and 3 demonstrate strain-selective activity against oral microorganisms. Journal of clinical microbiology 42, 1024\u20131029 (2004).","journal-title":"Journal of clinical microbiology"},{"key":"35530_CR57","unstructured":"Brouwer, C. P. J. M. et al. In Cohesive Journal of Microbiology & Infectious Disease, Vol. 1 (2018)."},{"key":"35530_CR58","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1002\/psc.2973","volume":"23","author":"K Singh","year":"2017","unstructured":"Singh, K., Shekhar, S., Yadav, Y., Xess, I. & Dey, S. DS6: antiCandidal, antibiofilm peptide against Candida tropicalis and exhibit synergy with commercial drug. Journal of Peptide Science 23, 228\u2013235 (2017).","journal-title":"Journal of Peptide Science"},{"key":"35530_CR59","doi-asserted-by":"publisher","first-page":"2365","DOI":"10.1016\/j.bbamem.2015.07.008","volume":"1848","author":"K Wang","year":"2015","unstructured":"Wang, K. et al. Antimicrobial peptide protonectin disturbs the membrane integrity and induces ROS production in yeast cells. Biochimica et Biophysica Acta (BBA)-Biomembranes 1848, 2365\u20132373 (2015).","journal-title":"Biochimica et Biophysica Acta (BBA)-Biomembranes"},{"key":"35530_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/srep09657","volume":"5","author":"KY Lum","year":"2015","unstructured":"Lum, K. Y. et al. Activity of novel synthetic peptides against Candida albicans. Scientific reports 5, 9657 (2015).","journal-title":"Scientific reports"},{"key":"35530_CR61","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1002\/yea.1241","volume":"22","author":"EJ Helmerhorst","year":"2005","unstructured":"Helmerhorst, E. J., Venuleo, C., Beri, A. & Oppenheim, F. G. Candida glabrata is unusual with respect to its resistance to cationic antifungal proteins. Yeast 22, 705\u2013714 (2005).","journal-title":"Yeast"},{"key":"35530_CR62","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1128\/EC.00284-08","volume":"7","author":"PW De Groot","year":"2008","unstructured":"De Groot, P. W. et al. The cell wall of the human pathogen Candida glabrata: differential incorporation of novel adhesin-like wall proteins. Eukaryotic cell 7, 1951\u20131964 (2008).","journal-title":"Eukaryotic cell"},{"key":"35530_CR63","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1128\/JCM.01915-07","volume":"46","author":"M Pfaller","year":"2008","unstructured":"Pfaller, M. et al. Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. Journal of Clinical Microbiology 46, 515\u2013521 (2008).","journal-title":"Journal of Clinical Microbiology"},{"key":"35530_CR64","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1080\/13693780802144339","volume":"47","author":"MM Panizo","year":"2009","unstructured":"Panizo, M. M., Revi\u00e1kina, V., Dolande, M. & Selgrad, S. Candida spp. in vitro susceptibility profile to four antifungal agents. Resistance surveillance study in Venezuelan strains. Medical mycology 47, 137\u2013143 (2009).","journal-title":"Medical mycology"},{"key":"35530_CR65","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1080\/13693780500220415","volume":"43","author":"R Pelletier","year":"2005","unstructured":"Pelletier, R., Alarie, I., Lagac\u00e9, R. & Walsh, T. J. Emergence of disseminated candidiasis caused by Candida krusei during treatment with caspofungin: case report and review of literature. Medical mycology 43, 559\u2013564 (2005).","journal-title":"Medical mycology"},{"key":"35530_CR66","first-page":"42","volume":"20","author":"G Ramage","year":"2001","unstructured":"Ramage, G., Wickes, B. & Lopez-Ribot, J. Biofilms of Candida albicans and their associated resistance to antifungal agents. American clinical laboratory 20, 42 (2001).","journal-title":"American clinical laboratory"},{"key":"35530_CR67","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1080\/08927014.2014.886108","volume":"30","author":"E Fonseca","year":"2014","unstructured":"Fonseca, E. et al. Effects of fluconazole on Candida glabrata biofilms and its relationship with ABC transporter gene expression. Biofouling 30, 447\u2013457 (2014).","journal-title":"Biofouling"},{"key":"35530_CR68","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.diagmicrobio.2015.06.015","volume":"83","author":"T Fernandes","year":"2015","unstructured":"Fernandes, T., Silva, S. & Henriques, M. Candida tropicalis biofilm\u2019s matrix\u2014involvement on its resistance to amphotericin B. Diagnostic microbiology and infectious disease 83, 165\u2013169 (2015).","journal-title":"Diagnostic microbiology and infectious disease"},{"key":"35530_CR69","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s00294-013-0400-3","volume":"59","author":"L Math\u00e9","year":"2013","unstructured":"Math\u00e9, L. & Van Dijck, P. Recent insights into Candida albicans biofilm resistance mechanisms. Current genetics 59, 251\u2013264 (2013).","journal-title":"Current genetics"},{"key":"35530_CR70","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1128\/AAC.00997-06","volume":"50","author":"PD Khot","year":"2006","unstructured":"Khot, P. D., Suci, P. A., Miller, R. L., Nelson, R. D. & Tyler, B. J. A small subpopulation of blastospores in Candida albicans biofilms exhibit resistance to amphotericin B associated with differential regulation of ergosterol and \u03b2-1, 6-glucan pathway genes. Antimicrobial agents and chemotherapy 50, 3708\u20133716 (2006).","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"35530_CR71","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1128\/AAC.46.6.1773-1780.2002","volume":"46","author":"D Kuhn","year":"2002","unstructured":"Kuhn, D., George, T., Chandra, J., Mukherjee, P. & Ghannoum, M. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrobial agents and chemotherapy 46, 1773\u20131780 (2002).","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"35530_CR72","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1128\/AEM.02439-06","volume":"73","author":"N Jain","year":"2007","unstructured":"Jain, N. et al. Biofilm formation by and antifungal susceptibility of Candida isolates from urine. Applied and environmental microbiology 73, 1697\u20131703 (2007).","journal-title":"Applied and environmental microbiology"},{"key":"35530_CR73","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s12223-017-0555-2","volume":"63","author":"M Pra\u017cy\u0144ska","year":"2018","unstructured":"Pra\u017cy\u0144ska, M., Bogiel, T. & Gospodarek-Komkowska, E. In vitro activity of micafungin against biofilms of Candida albicans, Candida glabrata, and Candida parapsilosis at different stages of maturation. Folia microbiologica 63, 209\u2013216 (2018).","journal-title":"Folia microbiologica"},{"key":"35530_CR74","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1099\/jmm.0.46569-0","volume":"55","author":"MA Al-Fattani","year":"2006","unstructured":"Al-Fattani, M. A. & Douglas, L. J. Biofilm matrix of Candida albicans and Candida tropicalis: chemical composition and role in drug resistance. Journal of medical microbiology 55, 999\u20131008 (2006).","journal-title":"Journal of medical microbiology"},{"key":"35530_CR75","doi-asserted-by":"crossref","unstructured":"Orozco, A.S. et al. Mechanism of Fluconazole Resistance in Candida krusei. 42, 2645\u20132649 (1998).","DOI":"10.1128\/AAC.42.10.2645"},{"key":"35530_CR76","first-page":"01","volume":"12","author":"P Wayne","year":"2002","unstructured":"Wayne, P. National committee for clinical laboratory standards. Performance standards for antimicrobial disc susceptibility testing 12, 01\u201353 (2002).","journal-title":"Performance standards for antimicrobial disc susceptibility testing"},{"key":"35530_CR77","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1111\/j.1600-0463.2007.apm_630.x","volume":"115","author":"S Stepanovi\u0107","year":"2007","unstructured":"Stepanovi\u0107, S. et al. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. Apmis 115, 891\u2013899 (2007).","journal-title":"Apmis"},{"key":"35530_CR78","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1111\/j.1567-1364.2012.00792.x","volume":"12","author":"G Pulcrano","year":"2012","unstructured":"Pulcrano, G., Panellis, D., De Domenico, G. & Rossano, F. & Catania, M.R. Ambroxol influences voriconazole resistance of Candida parapsilosis biofilm. FEMS yeast research 12, 430\u2013438 (2012).","journal-title":"FEMS yeast research"},{"key":"35530_CR79","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3109\/13693786.2011.580016","volume":"50","author":"HT Taff","year":"2012","unstructured":"Taff, H. T., Nett, J. E. & Andes, D. R. Comparative analysis of Candida biofilm quantitation assays. Sabouraudia 50, 214\u2013218 (2012).","journal-title":"Sabouraudia"},{"key":"35530_CR80","doi-asserted-by":"publisher","first-page":"20417","DOI":"10.3390\/ijms160920417","volume":"16","author":"F Barra","year":"2015","unstructured":"Barra, F. et al. Photodynamic and antibiotic therapy in combination to fight biofilms and resistant surface bacterial infections. International journal of molecular sciences 16, 20417\u201320430 (2015).","journal-title":"International journal of molecular sciences"},{"key":"35530_CR81","doi-asserted-by":"publisher","first-page":"3245","DOI":"10.2147\/IJN.S31219","volume":"7","author":"S Khan","year":"2012","unstructured":"Khan, S., Alam, F., Azam, A. & Khan, A. U. Gold nanoparticles enhance methylene blue\u2013induced photodynamic therapy: a novel therapeutic approach to inhibit Candida albicans biofilm. International journal of nanomedicine 7, 3245 (2012).","journal-title":"International journal of nanomedicine"},{"key":"35530_CR82","doi-asserted-by":"publisher","first-page":"e17755","DOI":"10.1371\/journal.pone.0017755","volume":"6","author":"P-W Tsai","year":"2011","unstructured":"Tsai, P.-W., Yang, C.-Y., Chang, H.-T. & Lan, C.-Y. Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates. PloS one 6, e17755 (2011).","journal-title":"PloS one"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-35530-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-35530-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-35530-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T12:02:43Z","timestamp":1671624163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-35530-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,4]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["35530"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-35530-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,4]]},"assertion":[{"value":"9 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"17570"}}