{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:16:06Z","timestamp":1790313366398,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"COLCIENCIAS 807\u20132018","award":["Contract RC No 715\u20132018"],"award-info":[{"award-number":["Contract RC No 715\u20132018"]}]},{"name":"COLCIENCIAS 807\u20132018","award":["FP44842-221-2018"],"award-info":[{"award-number":["FP44842-221-2018"]}]},{"name":"World Bank","award":["Contract RC No 715\u20132018"],"award-info":[{"award-number":["Contract RC No 715\u20132018"]}]},{"name":"World Bank","award":["FP44842-221-2018"],"award-info":[{"award-number":["FP44842-221-2018"]}]},{"name":"Convocatoria del Fondo de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n del Sistema General de Regal\u00edas, en el marco del Programa de Becas de Excelencia Doctoral del Bicentenario, definido en el art\u00edculo 45 de la ley 1942 de 2018, Bogot\u00e1, Colombia","award":["Contract RC No 715\u20132018"],"award-info":[{"award-number":["Contract RC No 715\u20132018"]}]},{"name":"Convocatoria del Fondo de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n del Sistema General de Regal\u00edas, en el marco del Programa de Becas de Excelencia Doctoral del Bicentenario, definido en el art\u00edculo 45 de la ley 1942 de 2018, Bogot\u00e1, Colombia","award":["FP44842-221-2018"],"award-info":[{"award-number":["FP44842-221-2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous reports have demonstrated that the peptide derived from LfcinB, R-1-R, exhibits anti-Candida activity, which is enhanced when combined with an extract from the Bidens pilosa plant. However, the mechanism of action remains unexplored. In this research, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both the SC5314 strain and a fluconazole-resistant isolate of Candida albicans after incubation with R-1-R. The proteomic data revealed that treatment with R-1-R led to the up-regulation of most differentially expressed proteins compared to the controls in both strains. These proteins are primarily involved in membrane and cell wall biosynthesis, membrane transport, oxidative stress response, the mitochondrial respiratory chain, and DNA damage response. Additionally, proteomic analysis of the C. albicans parental strain SC5314 treated with R-1-R combined with an ethanolic extract of B. pilosa was performed. The differentially expressed proteins following this combined treatment were involved in similar functional processes as those treated with the R-1-R peptide alone but were mostly down-regulated (data are available through ProteomeXchange with identifier PXD053558). Biological assays validated the proteomic results, evidencing cell surface damage, reactive oxygen species generation, and decreased mitochondrial membrane potential. These findings provide insights into the complex antifungal mechanisms of the R-1-R peptide and its combination with the B. pilosa extract, potentially informing future studies on natural product derivatives.<\/jats:p>","DOI":"10.3390\/ijms25168938","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T09:15:41Z","timestamp":1723799741000},"page":"8938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antifungal Synergy: Mechanistic Insights into the R-1-R Peptide and Bidens pilosa Extract as Potent Therapeutics against Candida spp. through Proteomics"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-8150","authenticated-orcid":false,"given":"Yerly","family":"Vargas-Casanova","sequence":"first","affiliation":[{"name":"Microbiology Department, Faculty of Sciences, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6855-0770","authenticated-orcid":false,"given":"Claudia Patricia","family":"Bravo-Chaucan\u00e9s","sequence":"additional","affiliation":[{"name":"Microbiology Department, Faculty of Sciences, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6718-5896","authenticated-orcid":false,"given":"Samuel de la C\u00e1mara","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Proteomics Unit, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Martinez-Lopez","sequence":"additional","affiliation":[{"name":"Microbiology and Parasitology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-0664","authenticated-orcid":false,"given":"Luc\u00eda","family":"Monteoliva","sequence":"additional","affiliation":[{"name":"Microbiology and Parasitology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3137-2600","authenticated-orcid":false,"given":"Concha","family":"Gil","sequence":"additional","affiliation":[{"name":"Microbiology and Parasitology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6915-8488","authenticated-orcid":false,"given":"Zuly Jenny","family":"Rivera-Monroy","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, Universidad Nacional of Colombia, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2449-1986","authenticated-orcid":false,"given":"Geison Modesti","family":"Costa","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Sciences, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6882-4397","authenticated-orcid":false,"given":"Javier Eduardo Garc\u00eda","family":"Casta\u00f1eda","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, Universidad Nacional of Colombia, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Marcela","family":"Parra-Giraldo","sequence":"additional","affiliation":[{"name":"Microbiology Department, Faculty of Sciences, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"},{"name":"Microbiology and Parasitology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/21505594.2021.2019950","article-title":"Pathogenesis and Virulence of Candida albicans","volume":"13","author":"Lopes","year":"2022","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4161\/viru.22913","article-title":"Candida albicans Pathogenicity Mechanisms","volume":"4","author":"Mayer","year":"2013","journal-title":"Virulence"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.micpath.2018.02.028","article-title":"Candida albicans\u2014Biology, Molecular Characterization, Pathogenicity, and Advances in Diagnosis and Control\u2014An Update","volume":"117","author":"Dadar","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"i4","DOI":"10.1093\/jac\/dkx444","article-title":"Changes in the Epidemiological Landscape of Invasive Candidiasis","volume":"73","author":"Lamoth","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.tim.2018.10.010","article-title":"Candida\u00a0albicans","volume":"27","author":"Wilson","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e268","DOI":"10.1016\/S1473-3099(24)00102-6","article-title":"Global Incidence and Mortality of Severe Fungal Disease","volume":"24","author":"Ikuta","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1021\/acs.chemrev.0c00199","article-title":"Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond","volume":"121","author":"Lee","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2147\/IDR.S118892","article-title":"Fluconazole Resistance in Candida Species: A Current Perspective","volume":"10","author":"Berkow","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the Emerging Threat of Antifungal Resistance to Human Health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_10","unstructured":"(2024, May 14). Antimicrobial Resistance in Candida | Fungal Diseases | CDC, Available online: https:\/\/www.cdc.gov\/fungal\/diseases\/candidiasis\/antifungal-resistant.html."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s44259-023-00007-2","article-title":"Molecular Mechanisms Governing Antifungal Drug Resistance","volume":"1","author":"Lee","year":"2023","journal-title":"Npj Antimicrob. Resist."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"114874","DOI":"10.1016\/j.addr.2023.114874","article-title":"New Antifungal Strategies: Drug Combination and Co-Delivery","volume":"198","author":"Zhu","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vargas-Casanova, Y., Bravo-Chaucan\u00e9s, C.P., Mart\u00ednez, A.X.H., Costa, G.M., Contreras-Herrera, J.L., Medina, R.F., Rivera-Monroy, Z.J., Garc\u00eda-Casta\u00f1eda, J.E., and Parra-Giraldo, C.M. (2023). Combining the Peptide RWQWRWQWR and an Ethanolic Extract of Bidens Pilosa Enhances the Activity against Sensitive and Resistant Candida albicans and C. auris Strains. J. Fungi, 9.","DOI":"10.3390\/jof9080817"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9691","DOI":"10.1002\/slct.202002101","article-title":"The Nonapeptide RWQWRWQWR: A Promising Molecule for Breast Cancer Therapy","volume":"5","year":"2020","journal-title":"ChemistrySelect"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17593","DOI":"10.1039\/D0RA02688C","article-title":"Selective Cytotoxic Effect against the MDA-MB-468 Breast Cancer Cell Line of the Antibacterial Palindromic Peptide Derived from Bovine Lactoferricin","volume":"10","author":"Vernot","year":"2020","journal-title":"RSC Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"221493","DOI":"10.1098\/rsos.221493","article-title":"Non-Natural Amino Acids into LfcinB-Derived Peptides: Effect in Their (i) Proteolytic Degradation and (Ii) Cytotoxic Activity against Cancer Cells","volume":"10","year":"2023","journal-title":"R. Soc. Open Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7236","DOI":"10.1002\/slct.202001329","article-title":"Palindromic Peptide LfcinB (21-25)Pal Exhibited Antifungal Activity against Multidrug-Resistant Candida","volume":"5","year":"2020","journal-title":"ChemistrySelect"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Huertas M\u00e9ndez, N.D.J., Vargas Casanova, Y., G\u00f3mez Chimbi, A.K., Hern\u00e1ndez, E., Leal Castro, A.L., Melo Diaz, J.M., Rivera Monroy, Z.J., and Garc\u00eda Casta\u00f1eda, J.E. (2017). Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076. Mol. J. Synth. Chem. Nat. Prod. Chem., 22.","DOI":"10.3390\/molecules22030452"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7239","DOI":"10.1039\/C9RA00708C","article-title":"Synergistic Bactericide and Antibiotic Effects of Dimeric, Tetrameric, or Palindromic Peptides Containing the RWQWR Motif against Gram-Positive and Gram-Negative Strains","volume":"9","author":"Cardenas","year":"2019","journal-title":"RSC Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0161-5890(03)00152-4","article-title":"Lactoferrin\u2014A Multifunctional Protein with Antimicrobial Properties","volume":"40","author":"Farnaud","year":"2003","journal-title":"Mol. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"807","DOI":"10.2174\/138161212799277617","article-title":"Therapeutic Potential of Host Defense Peptides in Antibiotic-Resistant Infections","volume":"18","author":"Afacan","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1472-765X.1994.tb00854.x","article-title":"Antifungal Properties of Lactoferricin B, a Peptide Derived from the N-terminal Region of Bovine Lactoferrin","volume":"18","author":"Bellamy","year":"1994","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.bbamem.2012.09.021","article-title":"A Novel Antimicrobial Peptide Derived from Modified N-Terminal Domain of Bovine Lactoferrin: Design, Synthesis, Activity against Multidrug-Resistant Bacteria and Candida","volume":"1828","author":"Mishra","year":"2013","journal-title":"Biochim. Biophys. Acta BBA-Biomembr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/j.peptides.2005.02.011","article-title":"Ultrastructural Effects of Antimicrobial Peptides from Bovine Lactoferrin on the Membranes of Candida albicans and Escherichia coli","volume":"26","author":"Nazmi","year":"2005","journal-title":"Peptides"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chang, C.-K., Kao, M.-C., and Lan, C.-Y. (2021). Antimicrobial Activity of the Peptide LfcinB15 against Candida albicans. J. Fungi, 7.","DOI":"10.3390\/jof7070519"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Angelini, P., Matei, F., Flores, G.A., Pellegrino, R.M., Vuguziga, L., Venanzoni, R., Tirillini, B., Emiliani, C., Orlando, G., and Menghini, L. (2021). Metabolomic Profiling, Antioxidant and Antimicrobial Activity of Bidens Pilosa. Processes, 9.","DOI":"10.3390\/pr9060903"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/j.1399-3011.2001.00821.x","article-title":"A Novel Bovine Lactoferrin Peptide, FKCRRWQWRM, Suppresses Candida Cell Growth and Activates Neutrophils","volume":"57","author":"Ueta","year":"2001","journal-title":"J. Pept. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1128\/EC.00133-10","article-title":"Interaction between the Candida albicans High-Osmolarity Glycerol (HOG) Pathway and the Response to Human \u03b2-Defensins 2 and 3","volume":"10","author":"Fanning","year":"2011","journal-title":"Eukaryot. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1128\/EC.00039-07","article-title":"Histatin 5 Initiates Osmotic Stress Response in Candida albicans via Activation of the Hog1 Mitogen-Activated Protein Kinase Pathway","volume":"6","author":"Vylkova","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_30","unstructured":"(2024, May 14). Candida Genome Database. Available online: http:\/\/www.candidagenome.org\/."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Xu, D., Jiang, B., Ketela, T., Lemieux, S., Veillette, K., Martel, N., Davison, J., Sillaots, S., Trosok, S., and Bachewich, C. (2007). Genome-Wide Fitness Test and Mechanism-of-Action Studies of Inhibitory Compounds in Candida albicans. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030092"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ibe, C., and Munro, C.A. (2021). Fungal Cell Wall Proteins and Signaling Pathways Form a Cytoprotective Network to Combat Stresses. J. Fungi, 7.","DOI":"10.3390\/jof7090739"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zaidi, K.U., Mani, A., Thawani, V., and Mehra, A. (2016). Total Protein Profile and Drug Resistance in Candida albicans Isolated from Clinical Samples. Mol. Biol. Int., 2016.","DOI":"10.1155\/2016\/4982131"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zarzosa-Moreno, D., Avalos-G\u00f3mez, C., Ram\u00edrez-Texcalco, L.S., Torres-L\u00f3pez, E., Ram\u00edrez-Mondrag\u00f3n, R., Hern\u00e1ndez-Ram\u00edrez, J.O., Serrano-Luna, J., and De La Garza, M. (2020). Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens. Molecules, 25.","DOI":"10.3390\/molecules25245763"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Polonelli, L., Ciociola, T., Sperind\u00e8, M., Giovati, L., D\u2019Adda, T., Galati, S., Travassos, L.R., Magliani, W., and Conti, S. (2017). Fungicidal Activity of Peptides Encoded by Immunoglobulin Genes. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-11396-6"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s11033-022-08093-7","article-title":"In Vitro Antifungal Activity of Shikonin against Candida albicans by Inducing Cellular Apoptosis and Necrosis","volume":"50","author":"Pang","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gbelska, Y., Hervay, N.T., Dzugasova, V., and Konecna, A. (2017). Measurement of Energy-Dependent Rhodamine 6G Efflux in Yeast Species. Bio-Protoc., 7.","DOI":"10.21769\/BioProtoc.2428"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1128\/AAC.43.11.2635","article-title":"Synergistic Fungistatic Effects of Lactoferrin in Combination with Antifungal Drugs against ClinicalCandida Isolates","volume":"43","author":"Kuipers","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1128\/AAC.42.7.1587","article-title":"Inhibition of Hyphal Growth of Azole-Resistant Strains of Candida albicans by Triazole Antifungal Agents in the Presence of Lactoferrin-Related Compounds","volume":"42","author":"Wakabayashi","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1091\/mbc.e09-01-0002","article-title":"Glucose Promotes Stress Resistance in the Fungal Pathogen Candida albicans","volume":"20","author":"Rodaki","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gomaa, S.E., Abbas, H.A., Mohamed, F.A., Ali, M.A.M., Ibrahim, T.M., Abdel Halim, A.S., Alghamdi, M.A., Mansour, B., Chaudhary, A.A., and Elkelish, A. (2024). The Anti-Staphylococcal Fusidic Acid as an Efflux Pump Inhibitor Combined with Fluconazole against Vaginal Candidiasis in Mouse Model. BMC Microbiol., 24.","DOI":"10.1186\/s12866-024-03181-z"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gonzalez-Jimenez, I., Perlin, D.S., and Shor, E. (2023). Reactive Oxidant Species Induced by Antifungal Drugs: Identity, Origins, Functions, and Connection to Stress-Induced Cell Death. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1276406"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1016\/j.bbamem.2015.07.008","article-title":"Antimicrobial Peptide Protonectin Disturbs the Membrane Integrity and Induces ROS Production in Yeast Cells","volume":"1848","author":"Wang","year":"2015","journal-title":"Biochim. Biophys. Acta BBA-Biomembr."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Seyedjavadi, S.S., Khani, S., Eslamifar, A., Ajdary, S., Goudarzi, M., Halabian, R., Akbari, R., Zare-Zardini, H., Imani Fooladi, A.A., and Amani, J. (2020). The Antifungal Peptide MCh-AMP1 Derived from Matricaria Chamomilla Inhibits Candida albicans Growth via Inducing ROS Generation and Altering Fungal Cell Membrane Permeability. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.03150"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1080\/10715762.2018.1511052","article-title":"Role of Calcium in Reactive Oxygen Species-Induced Apoptosis in Candida albicans: An Antifungal Mechanism of Antimicrobial Peptide, PMAP-23","volume":"53","author":"Kim","year":"2019","journal-title":"Free Radic. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bravo-Chaucan\u00e9s, C.P., Chitiva, L.C., Vargas-Casanova, Y., Diaz-Santoyo, V., Hern\u00e1ndez, A.X., Costa, G.M., and Parra-Giraldo, C.M. (2023). Exploring the Potential Mechanism of Action of Piperine against Candida albicans and Targeting Its Virulence Factors. Biomolecules, 13.","DOI":"10.3390\/biom13121729"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Stagos, D. (2019). Antioxidant Activity of Polyphenolic Plant Extracts. Antioxidants, 9.","DOI":"10.3390\/antiox9010019"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1091\/mbc.e05-06-0501","article-title":"Role of the Hog1 Stress-Activated Protein Kinase in the Global Transcriptional Response to Stress in the Fungal Pathogen Candida albicans","volume":"17","author":"Enjalbert","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Farrugia, G., and Balzan, R. (2012). Oxidative Stress and Programmed Cell Death in Yeast. Front. Oncol., 2.","DOI":"10.3389\/fonc.2012.00064"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.bbamcr.2008.01.023","article-title":"Reactive Oxygen Species and Yeast Apoptosis","volume":"1783","author":"Perrone","year":"2008","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_51","unstructured":"(2024, May 14). Molecular Biology of the Cell\u2014NCBI Bookshelf, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK21054\/."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Reyna-Beltr\u00e1n, E., M\u00e9ndez, C.I.B., Iranzo, M., Mormeneo, S., Luna-Arias, J.P., Reyna-Beltr\u00e1n, E., M\u00e9ndez, C.I.B., Iranzo, M., Mormeneo, S., and Luna-Arias, J.P. (2019). The Cell Wall of Candida albicans: A Proteomics View. Candida albicans, IntechOpen.","DOI":"10.5772\/intechopen.82348"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.jcis.2018.10.103","article-title":"Membrane Targeting Cationic Antimicrobial Peptides","volume":"537","author":"Ciumac","year":"2019","journal-title":"J. Colloid Interface Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0163-7827(90)90006-7","article-title":"An Overview of Lipids of Candida albicans","volume":"29","author":"Mishra","year":"1990","journal-title":"Prog. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8159562","DOI":"10.1155\/2019\/8159562","article-title":"Oxidative Stress in Microbial Diseases: Pathogen, Host, and Therapeutics","volume":"2019","author":"Novaes","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3390\/biom5010142","article-title":"Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans","volume":"5","author":"Dantas","year":"2015","journal-title":"Biomolecules"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"103998","DOI":"10.1016\/j.arabjc.2022.103998","article-title":"LfcinB-Derived Peptides: Specific and Punctual Change of an Amino Acid in Monomeric and Dimeric Sequences Increase Selective Cytotoxicity in Colon Cancer Cell Lines","volume":"15","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1021\/acsomega.2c07336","article-title":"Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines","volume":"8","year":"2023","journal-title":"ACS Omega"},{"key":"ref_59","unstructured":"(2024, May 14). CLSI M27-A3\u2014Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard-Third Edition. Available online: https:\/\/webstore.ansi.org\/standards\/clsi\/clsim27a3."},{"key":"ref_60","unstructured":"(2024, May 14). CLSI M27-S4\u2014Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Fourth Informational Supplement. Available online: https:\/\/webstore.ansi.org\/standards\/clsi\/clsim27s4."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/jac\/dkab454","article-title":"Genotypic, Proteomic, and Phenotypic Approaches to Decipher the Response to Caspofungin and Calcineurin Inhibitors in Clinical Isolates of Echinocandin-Resistant Candida Glabrata","volume":"77","author":"Monteoliva","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_62","unstructured":"(2024, May 14). Proteomics Sample Preparation | LC-MS Sample Preparation. Available online: https:\/\/www.preomics.com\/products\/ist."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1039\/b701483j","article-title":"Quantitative Shotgun Proteomics Using a Protease with Broad Specificity and Normalized Spectral Abundance Factors","volume":"3","author":"Zybailov","year":"2007","journal-title":"Mol. Biosyst."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"ELIXIR-709","DOI":"10.12688\/f1000research.24956.1","article-title":"Gprofiler2\u2014An R Package for Gene List Functional Enrichment Analysis and Namespace Conversion Toolset g:Profiler 2020","volume":"9","author":"Kolberg","year":"2020","journal-title":"F1000Research"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Quejada, L.F., Hernandez, A.X., Chitiva, L.C., Bravo-Chaucan\u00e9s, C.P., Vargas-Casanova, Y., Faria, R.X., Costa, G.M., and Parra-Giraldo, C.M. (2024). Unmasking the Antifungal Activity of Anacardium Occidentale Leaf Extract against Candida albicans. J. Fungi, 10.","DOI":"10.3390\/jof10070464"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1017\/S1431927612014298","article-title":"Facility Implementation and Comparative Performance Evaluation of Probe-Corrected TEM\/STEM with Schottky and Cold Field Emission Illumination","volume":"19","author":"Xin","year":"2013","journal-title":"Microsc. Microanal."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Li, X., Zhao, Y., Huang, X., Yu, C., Yang, Y., and Sun, S. (2017). Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00124"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Xue, Y.-P., Kao, M.-C., and Lan, C.-Y. (2019). Novel Mitochondrial Complex I-Inhibiting Peptides Restrain NADH Dehydrogenase Activity. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-50114-2"},{"key":"ref_69","first-page":"D543","article-title":"The PRIDE Database Resources in 2022: A Hub for Mass Spectrometry-Based Proteomics Evidences","volume":"50","author":"Bai","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"D1539","DOI":"10.1093\/nar\/gkac1040","article-title":"The ProteomeXchange Consortium at 10 Years: 2023 Update","volume":"51","author":"Deutsch","year":"2022","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8938\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:37:48Z","timestamp":1760110668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8938"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,16]]},"references-count":70,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168938"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168938","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,16]]}}}