{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T11:50:00Z","timestamp":1777549800605,"version":"3.51.4"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"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>The rapid emergence of invasive infections caused by azole-resistant <jats:italic>Candida tropicalis<\/jats:italic> has become a public health concern, and there is an urgent need for alternative treatment strategies. Studies have demonstrated the antibacterial effects of nisin, a well-known peptide naturally produced by <jats:italic>Lactococcus lactis<\/jats:italic> subsp. <jats:italic>lactis<\/jats:italic>. However, there is scant information about the antifungal effect of nisin against <jats:italic>C. tropicalis<\/jats:italic>. The present study aims to investigate the <jats:italic>in vitro<\/jats:italic> antifungal activity of nisin against clinical isolates of azole-resistant <jats:italic>C. tropicalis<\/jats:italic> strains, as well as its inhibitory effect on biofilm formation. A total of 35 <jats:italic>C. tropicalis<\/jats:italic> strains isolated from patients with invasive fungal infections were divided into the azole-resistant group and the azole-sensitive group, containing 21 and 14 strains, respectively. The relative expression levels of the <jats:italic>ERG11<\/jats:italic> and <jats:italic>UPC2<\/jats:italic> genes in the azole-resistant group were higher than those in the azole-sensitive group (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001), while no significant differences were observed in the expression levels of the <jats:italic>MDR1<\/jats:italic> and <jats:italic>CDR1<\/jats:italic> genes. The minimum inhibitory concentration of nisin against <jats:italic>C. tropicalis<\/jats:italic> ranged from 2 to 8\u2009\u03bcg\/mL. Nisin treatment inhibited the growth of azole-resistant <jats:italic>C. tropicalis,<\/jats:italic> with over a four-fold reduction in OD<jats:sub>600 nm<\/jats:sub> values observed at the 8-h time point, while it promoted the transition of <jats:italic>C. tropicalis<\/jats:italic> from the spore phase to the hyphal phase, as observed on cryo-scanning electron microscopy. The results of biofilm quantification using crystal violet staining indicated a significant decrease in OD<jats:sub>570 nm<\/jats:sub> values in the nisin-treated group compared to the controls (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.0001). Among the 21 azole-resistant <jats:italic>C. tropicalis<\/jats:italic> strains, the biofilm formation was inhibited in 17 strains (17\/21, 81%), and more than 85% inhibition of biofilm formation was observed in the representative strains. With regard to the molecular mechanisms, the expression of the <jats:italic>BCR1<\/jats:italic> and <jats:italic>UPC2<\/jats:italic> genes in the azole-resistant strains was down-regulated on nisin treatment (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). In conclusion, we demonstrated, for the first time, that nisin has antifungal activity and significant anti-biofilm activity against clinical isolates of azole-resistant <jats:italic>C. tropicalis<\/jats:italic> strains. Based on the findings, nisin could be a promising alternative antifungal agent for combating azole-resistant <jats:italic>C. tropicalis<\/jats:italic> infections.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1383953","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T04:30:35Z","timestamp":1715056235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Antifungal activity of nisin against clinical isolates of azole-resistant Candida tropicalis"],"prefix":"10.3389","volume":"15","author":[{"given":"Shuo","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueyue","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baiyuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanqing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1111\/j.1365-2672.2009.04312.x","article-title":"In vitro efficacy of nisin Z against Candida albicans adhesion and transition following contact with normal human gingival cells","volume":"107","author":"Akerey","year":"2009","journal-title":"J. Appl. Microbiol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1093\/cid\/cis021","article-title":"Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials","volume":"54","author":"Andes","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.ijfoodmicro.2004.11.007","article-title":"Mode of action of lipid II-targeting lantibiotics","volume":"101","author":"Bauer","year":"2005","journal-title":"Int. J. Food Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/5584_2016_7","article-title":"Fungal biofilms: update on resistance","volume":"931","author":"Borghi","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3389\/fmed.2018.00028","article-title":"Candida biofilms: threats, challenges, and promising strategies","volume":"5","author":"Cavalheiro","year":"2018","journal-title":"Front. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"105559","DOI":"10.1016\/j.jff.2023.105559","article-title":"Nisin and its application in oral diseases","volume":"105","author":"Chan","year":"2023","journal-title":"J. Funct. Foods"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1029412","DOI":"10.3389\/fmicb.2022.1029412","article-title":"Inactivation of Pseudomonas aeruginosa biofilms by thymoquinone in combination with nisin","volume":"13","author":"Chen","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref8","volume-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts","year":"2017"},{"key":"ref9","volume-title":"Performance standards for antifungal susceptibility testing of yeasts","year":"2022"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1208\/s12249-016-0477-3","article-title":"Development and characterization of nisin nanoparticles as potential alternative for the recurrent vaginal candidiasis treatment","volume":"17","author":"de Abreu","year":"2016","journal-title":"AAPS PharmSciTech"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.tifs.2009.01.056","article-title":"Nisin biotechnological production and application: a review","volume":"20","author":"de Arauz","year":"2009","journal-title":"Trends Food Sci. Technol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.3389\/fmicb.2018.01351","article-title":"Candida infections and therapeutic strategies: mechanisms of action for traditional and alternative agents","volume":"9","author":"de Oliveira Santos","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1139\/cjm-2022-0195","article-title":"Adhesion and biofilm formation by the opportunistic pathogen Candida tropicalis: what do we know?","volume":"69","author":"de Souza","year":"2023","journal-title":"Can. J. Microbiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e46884","DOI":"10.1371\/journal.pone.0046884","article-title":"Bioengineered nisin a derivatives with enhanced activity against both gram positive and gram negative pathogens","volume":"7","author":"Field","year":"2012","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1111\/j.1365-2958.2008.06279.x","article-title":"The generation of nisin variants with enhanced activity against specific gram-positive pathogens","volume":"69","author":"Field","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"508","DOI":"10.3389\/fmicb.2016.00508","article-title":"In vitro activities of Nisin and Nisin derivatives alone and in combination with antibiotics against Staphylococcus biofilms","volume":"7","author":"Field","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1111\/j.1751-7915.2010.00184.x","article-title":"Studies with bioengineered Nisin peptides highlight the broad-spectrum potency of Nisin V","volume":"3","author":"Field","year":"2010","journal-title":"Microb. Biotechnol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e0030122","DOI":"10.1128\/mbio.00301-22","article-title":"Extracellular vesicles regulate biofilm formation and yeast-to-hypha differentiation in Candida albicans","volume":"13","author":"Honorato","year":"2022","journal-title":"MBio"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/s12281-008-0026-y","article-title":"Phenotypic switching in Fungi","volume":"2","author":"Jain","year":"2008","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1080\/1040841X.2022.2112650","article-title":"Multiple potential strategies for the application of nisin and derivatives","volume":"49","author":"Khan","year":"2023","journal-title":"Crit. Rev. Microbiol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1111\/j.1365-2672.2008.03908.x","article-title":"Nisin Z inhibits the growth of Candida albicans and its transition from blastospore to hyphal form","volume":"105","author":"Le Lay","year":"2008","journal-title":"J. Appl. Microbiol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"957021","DOI":"10.3389\/ffunb.2022.957021","article-title":"The emerging threat antifungal-resistant Candida tropicalis in humans, animals, and environment","volume":"3","author":"Lima","year":"2022","journal-title":"Front. Fungal Biol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41522-018-0053-6","article-title":"Fighting biofilms with lantibiotics and other groups of bacteriocins","volume":"4","author":"Mathur","year":"2018","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/13693786.2011.560619","article-title":"Candida tropicalis biofilms: artificial urine, urinary catheters and flow model","volume":"49","author":"Negri","year":"2011","journal-title":"Med. Mycol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12903-022-02197-z","article-title":"Antimicrobial effects and mechanical properties of poly (methyl methacrylate) as an orthodontic acrylic resin containing curcumin-Nisin-poly (L-lactic acid) nanoparticle: an in vitro study","volume":"22","author":"Pourhajibagher","year":"2022","journal-title":"BMC Oral Health"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1002\/bab.2510","article-title":"Current advances in Candida tropicalis: yeast overview and biotechnological applications","volume":"70","author":"Queiroz","year":"2023","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"573614","DOI":"10.3389\/fmicb.2020.573614","article-title":"Insights in the antimicrobial potential of the natural nisin variant Nisin H","volume":"11","author":"Reiners","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.mib.2018.02.005","article-title":"Antifungal drug resistance: evolution, mechanisms, and impact","volume":"45","author":"Revie","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1128\/jb.16.4.211-229.1928","article-title":"Limiting factors in the lactic fermentation","volume":"16","author":"Rogers","year":"1928","journal-title":"J. Bacteriol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e0220000","DOI":"10.1371\/journal.pone.0220000","article-title":"Diabetic foot infections: application of a nisin-biogel to complement the activity of conventional antibiotics and antiseptics against Staphylococcus aureus biofilms","volume":"14","author":"Santos","year":"2019","journal-title":"PLoS One"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"104889","DOI":"10.1016\/j.micpath.2021.104889","article-title":"The relationship between biofilm formation and mortality in patients with Candida tropicalis candidemia","volume":"155","author":"Sasani","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.jprot.2015.09.011","article-title":"Comparative analysis of Staphylococcus epidermidis strains utilizing quantitative and cell surface shaving proteomics","volume":"130","author":"Solis","year":"2016","journal-title":"J. Proteome"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"313","DOI":"10.2174\/1389203720666190722152415","article-title":"Virulence factors in Candida species","volume":"21","author":"Staniszewska","year":"2020","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1111\/myc.13049","article-title":"Candida biofilm production is associated with higher mortality in patients with candidaemia","volume":"63","author":"Vit\u00e1lis","year":"2020","journal-title":"Mycoses"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13756-021-00890-2","article-title":"Candida tropicalis distribution and drug resistance is correlated with ERG11 and UPC2 expression","volume":"10","author":"Wang","year":"","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"702839","DOI":"10.3389\/fmicb.2021.702839","article-title":"Continual decline in azole susceptibility rates in Candida tropicalis over a 9-year period in China","volume":"12","author":"Wang","year":"","journal-title":"Front. Microbiol."},{"key":"ref37","year":"2022"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1111\/mmi.13247","article-title":"Regulation of filamentation in the human fungal pathogen Candida tropicalis","volume":"99","author":"Zhang","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"114258","DOI":"10.1016\/j.lwt.2022.114258","article-title":"Synergistic effect of propyl gallate and antibiotics against biofilms of Serratia marcescens and Erwinia carotovora in vitro","volume":"173","author":"Zhou","year":"2022","journal-title":"Lebensm. Wiss. Technol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"114573","DOI":"10.1016\/j.lwt.2023.114573","article-title":"Anti-virulence activity of dihydrocuminyl aldehyde and nisin against spoilage bacterium Pseudomonas aeruginosa XZ01","volume":"177","author":"Zhou","year":"","journal-title":"LWT-Food Sci. Technol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jgar.2023.01.005","article-title":"Prevalence, biofilm formation, and mass spectrometric characterization of linezolid-resistant Staphylococcus capitis isolated from a tertiary hospital in China","volume":"33","author":"Zhou","year":"","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e23738","DOI":"10.1002\/jcla.23738","article-title":"Association of different Candida species with catheter-related candidemia, and the potential antifungal treatments against their adhesion properties and biofilmforming capabilities","volume":"35","author":"Zuo","year":"2021","journal-title":"J. Clin. Lab. 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