{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:05:56Z","timestamp":1791655556202,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region, and is responsible for 85% to 90% of vulvovaginal candidiasis (VVC) cases. The development of drug resistance in C. albicans isolates after long-term therapy with fluconazole is an important complication to solve and new therapeutic strategies are required to target this organism and its pathogenicity. In the present study, phenyllactic acid (PLA) an important broad-spectrum antimicrobial compound was investigated for its antifungal and antivirulence activities against clinical isolates of C. albicans. Previously characterized strains of C. albicans isolates from women with VVC and C. albicans ATCC90028 were used to evaluate the antimicrobial and time dependent killing assay activity of PLA showing a MIC 7.5 mg mL\u22121 and a complete reduction of viable Candida cells detected by killing kinetics after 4 h of treatment with PLA. Additionally, PLA significantly reduced the biomass and the metabolic activity of C. albicans biofilms and impaired biofilm formation also with changes in ERG11, ALS3, and HWP1 genes expression as detected by qPCR. PLA eradicated pre-formed biofilms as showed also with confocal laser scanning microscopy (CLSM) observations. Furthermore, the compound prolonged the survival rate of Galleria mellonella infected by C. albicans isolates. These results indicate that PLA is a promising candidate as novel and safe antifungal agents for the treatment of vulvovaginal candidiasis.<\/jats:p>","DOI":"10.3390\/jof9030355","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:22:59Z","timestamp":1678857779000},"page":"355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Anti-Biofilm Activity of Phenyllactic Acid against Clinical Isolates of Fluconazole-Resistant Candida albicans"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-8837","authenticated-orcid":false,"given":"Angela","family":"Maione","sequence":"first","affiliation":[{"name":"Department of Biology, University of Naples \u2018Federico II\u2019, Via Cinthia, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Imparato","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples \u2018Federico II\u2019, Via Cinthia, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Buonanno","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples \u2018Federico II\u2019, Via Cinthia, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-3297","authenticated-orcid":false,"given":"Federica","family":"Carraturo","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples \u2018Federico II\u2019, Via Cinthia, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonetta","family":"Schettino","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Schettino","sequence":"additional","affiliation":[{"name":"Department of Ginecologia ed Ostetricia, AOU I Policlinico Universit\u00e0 della Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0174-0209","authenticated-orcid":false,"given":"Marilena","family":"Galdiero","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5874-3961","authenticated-orcid":false,"given":"Elisabetta","family":"de Alteriis","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples \u2018Federico II\u2019, Via Cinthia, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6805-0408","authenticated-orcid":false,"given":"Marco","family":"Guida","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples \u2018Federico II\u2019, Via Cinthia, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8116-0839","authenticated-orcid":false,"given":"Emilia","family":"Galdiero","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples \u2018Federico II\u2019, Via Cinthia, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Willems, H.M.E., Ahmed, S.S., Liu, J., Xu, Z., and Peters, B.M. (2020). Vulvovaginal Candidiasis: A Current Understanding and Burning Questions. J. Fungi, 6.","DOI":"10.3390\/jof6010027"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1473-3099(16)00095-5","article-title":"Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: A case study","volume":"16","author":"Calvet","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9703754","DOI":"10.1155\/2018\/9703754","article-title":"Risk factors of vulvovaginal candidiasis among women of reproductive age in Xi\u2019an: A cross-sectional study","volume":"2018","author":"Zeng","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1186\/s40001-022-00938-y","article-title":"Barriers and facilitators of adherence to treatment among women with vulvovaginal candidiasis: A qualitative study","volume":"27","author":"Erfaninejad","year":"2022","journal-title":"Eur. J. Med. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Anh, D.N., Hung, D.N., Tien, T.V., Dinh, V.N., Son, V.T., Luong, N.V., Van, N.T., Quynh, N.T.N., Van Tuan, N., and Tuan, L.Q. (2021). Prevalence, species distribution and antifungal susceptibility of Candida albicans causing vaginal discharge among symptomatic non-pregnant women of reproductive age at a tertiary care hospital, Vietnam. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06192-7"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Salazar, S.B., Sim\u00f5es, R.S., Pedro, N.A., Pinheiro, M.J., Carvalho, M.F.N.N., and Mira, N.P. (2020). An Overview on Conventional and Non-Conventional Therapeutic Approaches for the Treatment of Candidiasis and Underlying Resistance Mechanisms in Clinical Strains. J. Fungi, 6.","DOI":"10.3390\/jof6010023"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Arastehfar, A., Gabald\u00f3n, T., Garcia-Rubio, R., Jenks, J.D., Hoenigl, M., Salzer, H.J.F., Ilkit, M., Lass-Fl\u00f6rl, C., and Perlin, D.S. (2020). Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium. Antibiotics, 9.","DOI":"10.3390\/antibiotics9120877"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3389\/fmed.2016.00032","article-title":"The Future Liver Remnant in Patients Undergoing the Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) Maintains the Immunological Components of a Healthy Organ","volume":"3","author":"Anantha","year":"2016","journal-title":"Front. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111059","DOI":"10.1016\/j.lwt.2021.111059","article-title":"Effect of lactic acid bacteria and yeast fermentation on antimicrobial, antioxidative and metabolomic profile of naturally carbonated probiotic whey drink","volume":"142","author":"Kadyan","year":"2021","journal-title":"LWT"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/87559129.2019.1630636","article-title":"A Review of Selection Criteria for Starter Culture Development in the Food Fermentation Industry","volume":"36","author":"Junqueira","year":"2020","journal-title":"Food Rev. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.cej.2019.03.036","article-title":"Effects of furan-phosphamide derivative on flame retardancy and crystallization behaviors of poly(lactic acid)","volume":"369","author":"Sun","year":"2019","journal-title":"Chem. Eng. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.3389\/fmicb.2018.01373","article-title":"Detection of Antilisterial Activity of 3-Phenyllactic Acid Using Listeria innocua as a Model","volume":"9","author":"Sorrentino","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100413","DOI":"10.1016\/j.crfs.2022.100413","article-title":"Investigation of phenyllactic acid as a potent tyrosinase inhibitor produced by probiotics","volume":"6","author":"Shin","year":"2023","journal-title":"Curr. Res. Food Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9463","DOI":"10.3168\/jds.2022-22262","article-title":"Antibacterial activity and action target of phenyllactic acid against Staphylococcus aureus and its application in skim milk and cheese","volume":"105","author":"Jiang","year":"2022","journal-title":"J. Dairy Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.foodcont.2017.09.004","article-title":"Antibacterial and antibiofilm activity of phenyllactic acid against Enterobacter cloacae","volume":"84","author":"Liu","year":"2018","journal-title":"Food Control"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8223","DOI":"10.1007\/s00253-017-8546-4","article-title":"Mechanistic understanding of Phenyllactic acid mediated inhibition of quorum sensing and biofilm development in Pseudomonas aeruginosa","volume":"101","author":"Chatterjee","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.foodcont.2017.02.050","article-title":"Effects of phenyllactic acid as sanitizing agent for inactivation of Listeria monocytogenes biofilms","volume":"78","author":"Liu","year":"2017","journal-title":"Food Control"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103344","DOI":"10.1016\/j.fm.2019.103344","article-title":"Inhibition of biofilm formation and exopolysaccharide synthesis of Enterococcus faecalis by phenyllactic acid","volume":"86","author":"Liu","year":"2020","journal-title":"Food Microbiol."},{"key":"ref_19","unstructured":"Innis, M.A., Gelfand, D.H., Sninsky, J.J., and White, T.J. (1990). PCR Protocols, Academic Press."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11625","DOI":"10.1007\/s11033-022-07878-0","article-title":"Expression pattern of drug-resistance genes ERG11 and TAC1 in Candida albicans Clinical isolates","volume":"49","author":"Maleki","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_21","first-page":"1","article-title":"Method for antifungal disk diffusion susceptibility testing of yeasts, approved guideline","volume":"24","author":"CLSI","year":"2004","journal-title":"CLSI Doc. M44-A"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1590\/S0036-46652014000600004","article-title":"Susceptibility of Candida spp. isolated from blood cultures as evaluated using the M27-A3 and new M27-S4 approved breakpoints","volume":"56","author":"Santos","year":"2014","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.archoralbio.2016.10.013","article-title":"Antifungal activity, mode of action and anti-biofilm effects of Laurus nobilis Linnaeus essential oil against Candida spp.","volume":"73","author":"Peixoto","year":"2017","journal-title":"Arch. Oral Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Maione, A., La Pietra, A., de Alteriis, E., Mileo, A., De Falco, M., Guida, M., and Galdiero, E. (2022). Effect of Myrtenol and Its Synergistic Interactions with Antimicrobial Drugs in the Inhibition of Single and Mixed Biofilms of Candida auris and Klebsiella pneumoniae. Microorganisms, 10.","DOI":"10.3390\/microorganisms10091773"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00468-17","DOI":"10.1128\/AAC.00468-17","article-title":"Gepotidacin (GSK2140944) In Vitro Activity against Gram-Positive and Gram-Negative Bacteria","volume":"61","author":"Flamm","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0167-7012(00)00122-6","article-title":"A modified microtiter-plate test for quantification of staphylococcal biofilm formation","volume":"40","year":"2000","journal-title":"J. Microbiol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Maione, A., Bellavita, R., de Alteriis, E., Galdiero, S., Albarano, L., La Pietra, A., Guida, M., Parrilli, E., D\u2019Angelo, C., and Galdiero, E. (2022). WMR Peptide as Antifungal and Antibiofilm against Albicans and Non-Albicans Candida Species: Shreds of Evidence on the Mechanism of Action. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042151"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Maione, A., de Alteriis, E., Carraturo, F., Galdiero, S., Falanga, A., Guida, M., Di Cosmo, A., Maselli, V., and Galdiero, E. (2021). The Membranotropic Peptide gH625 to Combat Mixed Candida albicans\/Klebsiella pneumoniae Biofilm: Correlation between In Vitro Anti-Biofilm Activity and In Vivo Antimicrobial Protection. J. Fungi, 7.","DOI":"10.3390\/jof7010026"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ivanov, M., Kannan, A., Stojkovi\u0107, D.S., Glamo\u010dlija, J., Calhelha, R.C., Ferreira, I.C.F.R., Sanglard, D., and Sokovi\u0107, M. (2021). Flavones, Flavonols, and Glycosylated Derivatives\u2014Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity. Pharmaceuticals, 14.","DOI":"10.3390\/ph14010027"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bellavita, R., Maione, A., Merlino, F., Siciliano, A., Dardano, P., De Stefano, L., Galdiero, S., Galdiero, E., Grieco, P., and Falanga, A. (2022). Antifungal and Antibiofilm Activity of Cyclic Temporin L Peptide Analogues against Albicans and Non-Albicans Candida Species. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020454"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Baron, R., Taye, M., der Vaart, I.B., Uj\u010di\u010d-Voortman, J., Szajewska, H., Seidell, J.C., and Verhoeff, A. (2020). The relationship of prenatal antibiotic exposure and infant antibiotic administration with childhood allergies: A systematic review. BMC Pediatr., 20.","DOI":"10.1186\/s12887-020-02042-8"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1021\/acsinfecdis.0c00849","article-title":"Discovery of Piperidol Derivatives for Combinational Treatment of Azole-Resistant Candidiasis","volume":"7","author":"Yang","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_36","first-page":"612","article-title":"Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke","volume":"13","author":"Sacks","year":"2018","journal-title":"Int. J. Stroke"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s11947-008-0127-1","article-title":"Production and Characterization of an Antifungal Compound (3-Phenyllactic Acid) Produced by Lactobacillus plantarum Strain","volume":"3","author":"Prema","year":"2010","journal-title":"Food Bioprocess Technol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"116952","DOI":"10.1016\/j.jmatprotec.2020.116952","article-title":"Additive manufacturing of biodegradable iron-based particle reinforced polylactic acid composite scaffolds for tissue engineering","volume":"289","author":"Jiang","year":"2021","journal-title":"J. Mater. Process. Technol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00284-022-02833-5","article-title":"Streptococcus mutans and Candida albicans Biofilm Inhibitors Produced by Lactiplantibacillus plantarum CCFM8724","volume":"79","author":"Li","year":"2022","journal-title":"Curr. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s42770-018-0009-2","article-title":"Expression of fluconazole resistance-associated genes in biofilm from 23 clinical isolates of Candida albicans","volume":"50","author":"Shi","year":"2019","journal-title":"Braz. J. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e00130-16","DOI":"10.1128\/mSphere.00130-16","article-title":"Candida albicans Gene Deletion with a Transient CRISPR-Cas9 System","volume":"1","author":"Min","year":"2016","journal-title":"mSphere"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cmi.2015.09.018","article-title":"Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012-2013","volume":"22","author":"Rajendran","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"864","DOI":"10.3389\/fmicb.2020.00864","article-title":"Palmitic Acid Inhibits the Virulence Factors of Candida tropicalis: Biofilms, Cell Surface Hydrophobicity, Ergosterol Biosynthesis, and Enzymatic Activity","volume":"11","author":"Prasath","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Piatek, M., Sheehan, G., and Kavanagh, K. (2021). Galleria mellonella: The Versatile Host for Drug Discovery, In Vivo Toxicity Testing and Characterising Host-Pathogen Interactions. Antibiotics, 10.","DOI":"10.3390\/antibiotics10121545"}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/3\/355\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:55:16Z","timestamp":1760122516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/3\/355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["jof9030355"],"URL":"https:\/\/doi.org\/10.3390\/jof9030355","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]}}}