Candida albicans is a major opportunistic fungal pathogen, and its secreted SAP family genes contribute significantly to virulence, tissue invasion, and immune evasion. Among these, SAP5 is rapidly induced during infection and is closely associated with pathogenicity. Resistance to traditional antifungals such as azoles and polyenes is increasing, highlighting the need for alternative therapeutic agents. β-glucan polysaccharides, present in fungal and plant cell walls, exhibit immunomodulatory and antimicrobial properties; however, their effects on C. albicans virulence gene expression remain insufficiently investigated. In this study, 100 breast mastitis swabs were collected from female patients, yielding 25 Candida isolates, including 13 identified as C. albicans. Antifungal susceptibility was tested against nystatin, fluconazole, itraconazole, and clotrimazole. β-glucan was extracted from oats, purified, and applied at serial concentrations to determine the minimum inhibitory concentration (MIC). Polymerase chain reaction (PCR) was used to confirm the presence of the SAP5 gene, and quantitative real-time PCR (qPCR) was performed to assess SAP5 gene expression following treatment with β-glucan. Among the 13 C. albicans isolates, the highest resistance rate was to nystatin (61.5%), followed by fluconazole (53.8%), itraconazole (46.1%), and the lowest to clotrimazole (38.4%). Both fully resistant and fully susceptible isolates accounted for 30.8% of the total, while the remainder exhibited intermediate resistance. Oat β-glucan demonstrated a dose-dependent inhibitory effect on C. albicans growth, with MIC values varying among isolates. qPCR analysis revealed a significant 2.8 ± 0.4-fold decrease in SAP5 gene expression at 400 µg/ml β-glucan (p < 0.001, Student’s t-test). Oat-derived β-glucan exhibits antifungal activity against C. albicans and suppresses SAP5 expression, suggesting both direct inhibition and modulation of virulence. These results support its potential as a complementary antifungal agent amid increasing drug resistance.
F. C. Odds, Candida and Candidosis: A Review and Bibliography, 2nd ed., London, U.K.: Baillière Tindall, 1988.
M. A. Pfaller and D. J. Diekema, “Epidemiology of invasive candidiasis: a persistent public health problem,” Clinical Microbiology Reviews, vol. 20, no. 1, pp. 133-163, 2007.
K. Kaski and L. J. Kvist, “Deep breast pain during lactation: a case-control study in Sweden investigating the role of Candida albicans,” International Breastfeeding Journal, vol. 13, p. 21, 2018, [Online]. Available: https://doi.org/10.1186/s13006-018-0167-8.
F. L. Mayer, D. Wilson, and B. Hube, “Candida albicans pathogenicity mechanisms,” Virulence, vol. 4, no. 2, pp. 119-128, 2013.
B. Hube and J. R. Naglik, “Candida albicans proteinases: resolving the mystery of a gene family,” Microbiology, vol. 147, no. 8, pp. 1997-2005, 2001.
J. R. Naglik, C. A. Rodgers, P. J. Shirlaw, J. L. Dobbie, L. L. Fernandes-Naglik, D. Greenspan, N. Agabian, and S. J. Challacombe, “Differential expression of Candida albicans secreted aspartyl proteinase and phospholipase B genes in humans correlates with active oral and vaginal infections,” The Journal of Infectious Diseases, vol. 188, no. 3, pp. 469-479, 2003.
B. Hube, D. Sanglard, F. C. Odds, D. Hess, M. Monod, W. Schäfer, A. J. Brown, and N. A. Gow, “Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence,” Infection and Immunity, vol. 65, no. 9, pp. 3529-3538, Sept. 1997.
J. R. Naglik, S. J. Challacombe, and B. Hube, “Candida albicans secreted aspartyl proteinases in virulence and pathogenesis,” Microbiology and Molecular Biology Reviews, vol. 67, no. 3, pp. 400-428, Sept. 2003.
P. Staib and J. Morschhäuser, “Chlamydospore formation in Candida albicans and its regulation by the Efg1-Cph1 network,” Microbiology, vol. 153, no. 10, pp. 3360-3370, 2007.
S. G. Whaley, E. L. Berkow, J. M. Rybak, A. T. Nishimoto, K. S. Barker, and P. D. Rogers, “Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species,” Frontiers in Microbiology, vol. 7, p. 2173, 2017.
S. Costa-de-Oliveira and A. G. Rodrigues, “Candida albicans antifungal resistance and tolerance in bloodstream infections: The triad yeast-host-antifungal,” Microorganisms, vol. 8, no. 2, p. 154, Jan. 2020.
M. Castanheira, L. M. Deshpande, A. P. Davis, P. R. Rhomberg, and M. A. Pfaller, “Monitoring antifungal resistance in a global collection of invasive yeasts and molds: application of CLSI epidemiological cutoff values and whole-genome sequencing analysis for detection of azole resistance in Candida albicans,” Antimicrobial Agents and Chemotherapy, vol. 61, no. 10, pp. 10-1128, 2017.
H. Li, H. Chen, J. Shi, H. Jiang, X. Tang, Z. Zhou, Q. Fan, L. Zhang, and Y. Liu, “Combination of fluconazole with natural compounds: A promising strategy to manage resistant Candida albicans infections,” Fungal Biology Reviews, vol. 50, p. 100398, 2024.
B. A. Stone and A. E. Clarke, Chemistry and Biology of (1→3)-β-Glucans, Bundoora, Victoria, Australia: La Trobe University Press, 1992.
A. Lazaridou and C. G. Biliaderis, “Molecular aspects of cereal β-glucan functionality: physical properties, technological applications, and physiological effects,” Cereal Chemistry, vol. 46, no. 2, pp. 101-118, 2007.
G. D. Brown and S. Gordon, “A new receptor for β-glucans,” Nature, vol. 413, no. 6851, pp. 36-37, 2001.
M. G. Netea, L. A. B. Joosten, E. Latz, K. H. G. Mills, G. Natoli, H. G. Stunnenberg, L. A. J. O’Neill, and R. J. Xavier, “Trained immunity: a program of innate immune memory in health and disease,” Science, vol. 352, no. 6284, p. aaf1098, 2016.
G. C. Chan, W. K. Chan, and D. M. Sze, “The effects of β-glucan on human immune and cancer cells,” Journal of Hematology & Oncology, vol. 2, p. 25, 2009.
P. Vandeputte, S. Ferrari, and A. T. Coste, “Antifungal resistance and new strategies to control fungal infections,” International Journal of Microbiology, vol. 2012, p. 713687, 2012.
J. J. Volman, J. D. Ramakers, and J. Plat, “Dietary modulation of immune function by β-glucans,” Physiology & Behavior, vol. 94, no. 2, pp. 276-284, 2008.
V. Vetvicka, L. Vannucci, P. Sima, and J. Richter, “Beta-glucan: supplement or drug? From laboratory to clinical trials,” Molecules, vol. 24, no. 7, p. 1251, 2019.
C. H. Yun, A. Estrada, A. Van Kessel, B. C. Park, and B. Laarveld, “Beta-glucan, extracted from oat, enhances disease resistance against bacterial and parasitic infections,” FEMS Immunology & Medical Microbiology, vol. 35, no. 1, pp. 67-75, 2003, [Online]. Available: https://doi.org/10.1016/S0928-8244(02)00460-1.
S. H. Mahmoud and S. N. Yassein, “The effectiveness of β-glucan in the treatment of caprine mastitis induced by Candida albicans,” The Iraqi Journal of Veterinary Medicine, vol. 48, no. 2, pp. 81-87, 2024.
J. S. Piotrowski, H. Okada, F. Lu, S. C. Li, L. Hinchman, A. Ranjan, D. L. Smith, A. J. Higbee, A. Ulbrich, J. J. Coon, and R. Deshpande, “Plant-derived antifungal agent poacic acid targets β-1,3-glucan,” Proceedings of the National Academy of Sciences, vol. 112, no. 12, pp. E1490-E1497, 2015.
Clinical and Laboratory Standards Institute (CLSI), Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts; Approved Guideline, CLSI document M44, 3rd ed., Wayne, PA: Clinical and Laboratory Standards Institute, 2018.
R. S. Bhatty, “Laboratory and pilot plant extraction and purification of β-glucans from hull-less barley and oat brans,” Journal of Cereal Science, vol. 22, no. 2, pp. 163-170, 1995.
Clinical and Laboratory Standards Institute (CLSI), Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard Fourth Edition (M27-A4), Wayne, PA: CLSI, 2022.
D. W. Russell and J. Sambrook, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 2001.
T. J. White, T. Bruns, S. Lee, and J. Taylor, “Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics,” in PCR Protocols: A Guide to Methods and Applications, M. A. Innis, D. H. Gelfand, J. J. Sninsky, and T. J. White, Eds., San Diego, CA: Academic Press, 1990, pp. 315-322.
C. L. Schoch et al., “Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for fungi,” Proceedings of the National Academy of Sciences of the USA, vol. 109, no. 16, pp. 6241-6246, 2012.
K. J. Livak and T. D. Schmittgen, “Analysis of relative gene expression data using real-time quantitative PCR and the 2⁻ΔΔCq method,” Methods, vol. 25, no. 4, pp. 402-408, 2001.
C. J. Barelle, V. M. Duncan, A. J. Brown, N. A. Gow, and F. C. Odds, “Azole antifungals induce up-regulation of SAP4, SAP5 and SAP6 secreted proteinase genes in filamentous Candida albicans cells in vitro and in vivo,” J. Antimicrob. Chemother., vol. 61, no. 2, pp. 315-322, 2008.
J. R. Naglik, D. Moyes, J. Makwana, P. Kanzaria, E. Tsichlaki, G. Weindl, A. R. Tappuni, C. A. Rodgers, A. J. Woodman, S. J. Challacombe, and M. Schaller, “Quantitative expression of the Candida albicans secreted aspartyl proteinase gene family in human oral and vaginal candidiasis,” Microbiology, vol. 154, no. 11, pp. 3266-3280, 2008.
L. Hanna and S. A. Cruz, “Candida mastitis: a case report,” The Permanente Journal, vol. 15, no. 1, pp. 62-64, 2011.
Y. Merad, H. Derrar, M. Belkacemi, A. Drici, and Z. Belmokhtar, “Candida albicans mastitis in a breastfeeding woman: an under-recognized diagnosis,” Cureus, vol. 12, no. 12, p. e12026, 2020, [Online]. Available: https://doi.org/10.7759/cureus.12026.
E. L. Berkow and S. R. Lockhart, “Fluconazole resistance in Candida species: a current perspective,” Infection and Drug Resistance, vol. 10, pp. 237-245, 2017, [Online]. Available: https://doi.org/10.2147/IDR.S118892.
S. Rehab, A. M. Al-Maliki, and I. A. Zouhair, “Antifungal resistance of Candida species isolated from Iraqi women infected with vulvovaginal candidiasis,” Al-Qadisiyah Medical Journal, vol. 7, no. 11, pp. 117-127, 2011.
A. Nakashima, K. Yamada, O. Iwata, R. Sugimoto, K. Atsuji, T. Ogawa, N. Ishibashi-Ohgo, and K. Suzuki, “β-glucan in foods and its physiological functions,” Journal of Nutritional Science and Vitaminology, vol. 64, no. 1, pp. 8-17, 2018.
B. Du, M. Meenu, H. Liu, and B. Xu, “A concise review on the molecular structure and function relationship of β-glucan,” International Journal of Molecular Sciences, vol. 20, no. 16, p. 4032, 2019, [Online]. Available: https://doi.org/10.3390/ijms20164032.
G. D. Brown and S. Gordon, “Immune recognition of fungal β-glucans,” Cellular Microbiology, vol. 7, no. 4, pp. 471-479, 2005.
I. V. Ene, L. A. Walker, M. Schiavone, K. K. Lee, H. Martin-Yken, E. Dague, N. A. R. Gow, C. A. Munro, and A. J. P. Brown, “Cell wall remodeling enzymes modulate Candida albicans recognition by dectin-1 and alter β-glucan exposure during growth and morphogenesis,” mBio, vol. 6, no. 6, p. e00986-15, 2015, [Online]. Available: https://doi.org/10.1128/mBio.00986-15.
E. Román, D. M. Arana, C. Nombela, R. Alonso-Monge, and J. Pla, “MAP kinase pathways as regulators of fungal virulence,” Trends in Microbiology, vol. 15, no. 4, pp. 181-190, 2007, [Online]. Available: https://doi.org/10.1016/j.tim.2007.02.001.
J. Kim and P. Sudbery, “Candida albicans, a major human fungal pathogen,” Journal of Microbiology, vol. 49, no. 2, pp. 171-177, 2011, [Online]. Available: https://doi.org/10.1007/s12275-011-1064-7.