{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:08:39Z","timestamp":1779329319165,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,3]],"date-time":"2018-02-03T00:00:00Z","timestamp":1517616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research","award":["RBFR136GFF"],"award-info":[{"award-number":["RBFR136GFF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The isolation and characterization from the sand fly Phlebotomus perniciosus of a Wickerhamomyces anomalus yeast strain (Wa1F1) displaying the killer phenotype was recently reported. In the present work, the killer toxin (KT) produced by Wa1F1 was purified and characterized, and its antimicrobial activity in vitro was investigated against fluconazole- susceptible and -resistant clinical isolates and laboratory strains of Candida albicans and C. glabrata displaying known mutations. Wa1F1-KT showed a differential killing ability against different mutant strains of the same species. The results may be useful for the design of therapeutic molecules based on Wa1F1-KT and the study of yeast resistance mechanisms.<\/jats:p>","DOI":"10.3390\/toxins10020068","type":"journal-article","created":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T04:29:42Z","timestamp":1517804982000},"page":"68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Candidacidal Activity of a Novel Killer Toxin from Wickerhamomyces anomalus against Fluconazole-Susceptible and -Resistant Strains"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7514-1789","authenticated-orcid":false,"given":"Laura","family":"Giovati","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Santinoli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-2545","authenticated-orcid":false,"given":"Tecla","family":"Ciociola","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Milan, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Bandi","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Milan, 20133 Milan, Italy"},{"name":"Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Ospedale \u201cLuigi Sacco\u201d, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Ricci","sequence":"additional","affiliation":[{"name":"School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Epis","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Milan, 20133 Milan, Italy"},{"name":"Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Ospedale \u201cLuigi Sacco\u201d, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9973-8352","authenticated-orcid":false,"given":"Stefania","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,3]]},"reference":[{"key":"ref_1","unstructured":"Bevan, E.A., and Makower, M. (1963). The Physiological Basis of the Killer Character in Yeast, Pergamon Press. XIth Int Congr Genet, Leiden, The Netherlands."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1128\/CMR.10.3.369","article-title":"Yeast killer systems","volume":"10","author":"Magliani","year":"1997","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"588","DOI":"10.3390\/microorganisms3040588","article-title":"Bioprotective role of yeasts","volume":"3","author":"Muccilli","year":"2015","journal-title":"Microorganisms"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/j.1567-1364.2007.00238.x","article-title":"The use of killer sensitivity patterns for biotyping yeast strains: The state of the art, potentialities and limitations","volume":"7","author":"Buzzini","year":"2007","journal-title":"FEMS Yeast Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-1-60327-151-6_11","article-title":"Biotyping of Candida albicans and other fungi by yeast killer toxins sensitivity","volume":"499","author":"Polonelli","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10482-010-9496-3","article-title":"From Pichia anomala killer toxin through killer antibodies to killer peptides for a comprehensive anti-infective strategy","volume":"99","author":"Polonelli","year":"2011","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10482-010-9491-8","article-title":"Pichia anomala: Cell physiology and biotechnology relative to other yeasts","volume":"99","author":"Walker","year":"2011","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12936-015-1059-7","article-title":"A yeast strain associated to Anopheles mosquitoes produces a toxin able to kill malaria parasites","volume":"15","author":"Valzano","year":"2016","journal-title":"Malaria J."},{"key":"ref_9","first-page":"1","article-title":"New killer toxins of halophilic Hansenula anomala","volume":"52","author":"Kagiyama","year":"1988","journal-title":"Agric. Biol. Chem."},{"key":"ref_10","first-page":"395","article-title":"Physiological characteristics of the biocontrol yeast Pichia anomala J121","volume":"2","author":"Fredlund","year":"2002","journal-title":"FEMS Yeast Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Perez, M.F., Contreras, L., Garnica, N.M., Fern\u00e1ndez-Zenoff, M.V., Far\u00edas, M.E., Sepulveda, M., Ramallo, J., and Dib, J.R. (2016). Native killer yeasts as biocontrol agents of postharvest fungal diseases in lemons. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165590"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.micres.2006.09.002","article-title":"A marine killer yeast against the pathogenic yeast strain in crab (Portunus trituberculatus) and an optimization of the toxin production","volume":"162","author":"Wang","year":"2007","journal-title":"Microbiol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1111\/j.1462-2920.2010.02395.x","article-title":"The yeast Wickerhamomyces anomalus (Pichia anomala) inhabits the midgut and reproductive system of the Asian malaria vector Anopheles stephensi","volume":"13","author":"Ricci","year":"2011","journal-title":"Environ. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cappelli, A., Ulissi, U., Valzano, M., Damiani, C., Epis, S., Gabrielli, M.G., Conti, S., Polonelli, L., Bandi, C., and Favia, G. (2014). A Wickerhamomyces anomalus killer strain in the malaria vector Anopheles stephensi. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095988"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/mve.12149","article-title":"Isolation of a Wickerhamomyces anomalus yeast strain from the sandfly Phlebotomus perniciosus, displaying the killer phenotype","volume":"30","author":"Martin","year":"2016","journal-title":"Med. Vet. Entomol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1567-1364.2005.00004.x","article-title":"Biotechnology, physiology and genetics of the yeast Pichia anomala","volume":"6","author":"Passoth","year":"2006","journal-title":"FEMS Yeast Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1439-0507.1996.tb00089.x","article-title":"Risk assessment of fungi reported from humans and animals","volume":"39","year":"1996","journal-title":"Mycoses"},{"key":"ref_18","first-page":"577","article-title":"A rapid qPCR method to investigate the circulation of the yeast Wickerhamomyces anomalus in humans","volume":"38","author":"Epis","year":"2015","journal-title":"New Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1439-0507.2006.01303.x","article-title":"In vitro activity of panomycocin, a novel exo-\u03b2-1,3-glucanase isolated from Pichia anomala NCYC 434, against dermatophytes","volume":"50","year":"2007","journal-title":"Mycoses"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tay, S.-T., Lim, S.-L., and Tan, H.-W. (2014). Growth inhibition of Candida species by Wickerhamomyces anomalus mycocin and a lactone compound of Aureobasidium pullulans. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-439"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s00284-016-1135-4","article-title":"Susceptibility of Candida albicans isolated from blood to Wickerhamomyces anomalous mycocins","volume":"73","author":"Paris","year":"2016","journal-title":"Curr. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lion, T. (2017). The changing epidemiology of invasive fungal infections. Human Fungal Pathogen Identification: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-4939-6515-1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/1469-0691.12539","article-title":"Global trends in the distribution of Candida species causing candidemia","volume":"20","author":"Guinea","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.clinmicnews.2014.08.001","article-title":"Current epidemiology of Candida infection","volume":"36","author":"Lockhart","year":"2014","journal-title":"Clin. Microbiol. Newsl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/1469-0691.12440","article-title":"Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: A 6-year prospective candidaemia survey from the fungal infection network of Switzerland","volume":"20","author":"Orasch","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/mmy\/myv114","article-title":"Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia-Pacific region","volume":"54","author":"Tan","year":"2016","journal-title":"Med. Mycol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1128\/AAC.39.11.2378","article-title":"Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters","volume":"39","author":"Sanglard","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1128\/AAC.43.11.2753","article-title":"The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents","volume":"43","author":"Sanglard","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1128\/EC.00151-07","article-title":"Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates","volume":"6","author":"Coste","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1128\/EC.00069-09","article-title":"Functional analysis of cis- and trans-acting elements of the Candida albicans CDR2 promoter with a novel promoter reporter system","volume":"8","author":"Coste","year":"2009","journal-title":"Eukaryot. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ferrari, S., Ischer, F., Calabrese, D., Posteraro, B., Sanguinetti, M., Fadda, G., Rohde, B., Bauser, C., Bader, O., and Sanglard, D. (2009). Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000268"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1128\/cdli.4.2.142-146.1997","article-title":"Monoclonal yeast killer toxin-like candidacidal anti-idiotypic antibodies","volume":"4","author":"Polonelli","year":"1997","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/mmy.39.5.395.400","article-title":"Immuno-crossreactivity of an anti-Pichia anomala killer toxin monoclonal antibody with a Williopsis saturnus var. mrakii killer toxin","volume":"39","author":"Guyard","year":"2001","journal-title":"Med. Mycol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1007\/BF03402032","article-title":"Involvement of beta-glucans in the wide-spectrum antimicrobial activity of Williopsis saturnus var. mrakii MUCL 41968 killer toxin","volume":"8","author":"Guyard","year":"2002","journal-title":"Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.clindermatol.2009.12.014","article-title":"Candidosis, a new challenge","volume":"28","year":"2010","journal-title":"Clin. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1128\/CMR.00029-06","article-title":"Epidemiology of invasive candidiasis: A persistent public health problem","volume":"20","author":"Pfaller","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"204237","DOI":"10.1155\/2013\/204237","article-title":"Candida infections, causes, targets, and resistance mechanisms: Traditional and alternative antifungal agents","volume":"2013","author":"Spampinato","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1128\/jcm.17.5.774-780.1983","article-title":"Killer system: A simple method for differentiating Candida albicans strains","volume":"17","author":"Polonelli","year":"1983","journal-title":"J. Clin. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/BF00437542","article-title":"Production of yeast killer toxin in experimentally infected animals","volume":"110","author":"Polonelli","year":"1990","journal-title":"Mycopathologia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s10482-012-9855-3","article-title":"A novel killer toxin produced by the marine-derived yeast Wickerhamomyces anomalus YF07b","volume":"103","author":"Guo","year":"2013","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1271\/bbb.68.685","article-title":"Isolation and characterization of the K5-type yeast killer protein and its homology with an exo-beta-1,3-glucanase","volume":"68","year":"2004","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3354\/dao01943","article-title":"Marine killer yeasts active against a yeast strain pathogenic to crab Portunus trituberculatus","volume":"80","author":"Wang","year":"2008","journal-title":"Dis. Aquat. Organ."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/02681219880000301","article-title":"Effect of Pichia anomala killer toxin on Candida albicans","volume":"36","author":"Mathews","year":"1998","journal-title":"Med. Mycol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Polonelli, L., Beninati, C., Teti, G., Felici, F., Ciociola, T., Giovati, L., Sperind\u00e8, M., Passo, C.L., Pernice, I., and Domina, M. (2014). Yeast killer toxin-like candidacidal Ab6 antibodies elicited through the manipulation of the idiotypic cascade. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105727"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1099\/00221287-130-5-1217","article-title":"Isolation and structure of glucan from regenerating spheroplasts of Candida albicans","volume":"130","author":"Gopal","year":"1984","journal-title":"Microbiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.enzmictec.2005.11.024","article-title":"Killer toxin of Pichia anomala NCYC 432; purification, characterization and its exo-\u03b2-1,3-glucanase activity","volume":"39","author":"Acun","year":"2006","journal-title":"Enzyme Microb. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.biotechadv.2009.01.002","article-title":"Production, characterization and gene cloning of the extracellular enzymes from the marine-derived yeasts and their potential applications","volume":"27","author":"Chi","year":"2009","journal-title":"Biotechnol. Adv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00436668","article-title":"Potential therapeutic effect of yeast killer toxin","volume":"96","author":"Polonelli","year":"1986","journal-title":"Mycopathologia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1128\/AAC.42.12.3065","article-title":"Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains","volume":"42","author":"Franz","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1086\/524071","article-title":"Resistance to antifungal agents: Mechanisms and clinical impact","volume":"46","author":"Kanafani","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s00203-015-1146-8","article-title":"ERG11 mutations and expression of resistance genes in fluconazole-resistant Candida albicans isolates","volume":"197","author":"Xu","year":"2015","journal-title":"Arch. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1128\/EC.3.6.1639-1652.2004","article-title":"TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2","volume":"3","author":"Coste","year":"2004","journal-title":"Eukaryot. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10295-006-0184-2","article-title":"Inulinase production by a marine yeast Pichia guilliermondii and inulin hydrolysis by the crude inulinase","volume":"34","author":"Gong","year":"2007","journal-title":"J. Ind. Microbiol. Biotechnol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/2\/68\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:53:39Z","timestamp":1760194419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/2\/68"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,3]]},"references-count":53,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2]]}},"alternative-id":["toxins10020068"],"URL":"https:\/\/doi.org\/10.3390\/toxins10020068","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,3]]}}}