Saponins from Mimusops laurifolia target some key virulence factors in Candida albicans

Mostafa, Hayam M.A.; Raslan, Mai; Khairalla, Ahmed; Abd El Fattah, Medhat; El-Gendy, Ahmed O.

doi:10.22034/ecc.2023.406976.1664

Document Type : Original Research Article

Authors

¹ Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, 62511, Egypt

² Beni-Suef University Hospitals, Faculty of Medicine, Beni-Suef University, 62511, Egypt

³ Microbiology and Immunology Department, Faculty of Pharmacy, Beni-Suef University, Egypt

⁴ Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada

⁵ Department of Botany and Microbiology, Faculty of Science, Beni-Suef University, Egypt

10.22034/ecc.2023.406976.1664

Abstract

Mimusops laurifolia (The Tree of Life, as it was known by the ancient Egyptians) belongs to the Mimusops genus, which has been used in folk medicine for a very long time. Recently, it has been concluded that a crude extract containing the saponins from the leaves of M. laurifolia has promising antifungal activity against Candida albicans. This fungus is a widely known opportunistic pathogen linked to systemic and chronic infections. As a result, the current study aims to investigate the anti-virulence potential of these saponins extract against C. albicans at the molecular level in an attempt to better understand how these saponins might function as an antifungal agent against C. albicans. Real-time PCR was used to quantify the relative gene expression levels of critical virulence factors in C. albicans cells treated with saponins versus untreated cells. The potential of these saponins as antifungal agents is likely to be attributed to their gene-regulatory activity, as the expression of some key genes in C. albicans (involved in invasion, survival, and adhesion, such as SAP3, SAP5, and ALS3) was strongly downregulated in saponin-exposed Candida cells. Generally, these data show that M. laurifolia-derived saponins may be efficient inhibitors and virulence modulators of C. albicans. Thus, the current study broadens our knowledge about saponin's potential antifungal properties. Moreover, our discovery of a strong suppressor that acts specifically on virulence-related genes paves the way to develop an oriented class of antifungal drugs.

Graphical Abstract

Keywords

Main Subjects

Biochemistry

References

[1] N. Martins, I.C. Ferreira, L. Barros, S. Silva, M. Henriques, Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment, Mycopathologia., 2014, 177, 223-240. ‎[Crossref], [Google Scholar], [Publisher]

[2] N.M. Muna, A.D.W. Widodo, P.D. Endraswari, M.V. Arfijanto, Correlation Between the Bacterial and Fungal Profiles from the Clinical Specimens with the CD4 Counts and the NLR Values of HIV/AIDS Patients at Tertiary Referral Hospital in Indonesia, J. Med. Chem. Sci., 2023, 6, 2111-2127. ‎[Crossref], [Google Scholar], [Publisher]

[3] H.J. Naser, F.M. Abdul-Ameer, Evaluation of the Effect of Lemongrass Essential Oil on Candida Albicans Adhesion on Heat Cured Acrylic Based Soft Lining Material, J. Med. Chem. Sci., 2023, 6, 1685-1695. ‎[Crossref], [Google Scholar], [Publisher]

[4] D. Murdiyanto, A. Faizah, M.D. Mustikaningrum, Inhibition of Garlic Ethanol Extracts (Allium Sativum L.) as a Solvent in Alginate Impression Materials in the Growth of Candida Albicans, J. Med. Chem. Sci., 2022, 5, 144-152. ‎[Crossref], [Google Scholar], [Publisher]

[5] D.U.J. N’Guessan, S. Coulibaly, F.K.K. Kassi, P. Delaye, M. Penichon, C. Enguehard-Gueiffier, H. Allouchi, M. Ouattara, Synthesis and SAR of Imidazo[1,2-a] Pyridinyl-Phenylacrylonitrile Derivatives as Potent Anticandidosis Agents, J. Med. Chem. Sci., 2021, 4, 554-563. ‎[Crossref], [Google Scholar], [Publisher]

[6] S.M. Noble, B.A. Gianetti, J.N. Witchley, Candida albicans cell-type switching and functional plasticity in the mammalian host, Nat. Rev. Microbiol., 2017, 15, 96-108. ‎[Crossref], [Google Scholar], [Publisher]

[7] I.D. Jacobsen, D. Wilson, B. Wächtler, S. Brunke, J.R. Naglik, B. Hube, Candida albicans dimorphism as a therapeutic target, Expert. Rev. Anti. Infect. Ther., 2012, 10, 85-93. ‎[Crossref], [Google Scholar], [Publisher]

[8] R.A. Hall, M.C. Noverr, Fungal interactions with the human host: exploring the spectrum of symbiosis, Curr. Opin. Microbiol., 2017, 40, 58-64. ‎[Crossref], [Google Scholar], [Publisher]

[9] J. Ni, G.D. Wu, L. Albenberg, V.T. Tomov, Gut microbiota and IBD: causation or correlation?, Nat. Rev. Gastroenterol. Hepatol., 2017,14, 573-584. ‎[Crossref], [Google Scholar], [Publisher]

[10] B.B. Finlay, S. Falkow, Common themes in microbial pathogenicity revisited, Microbiol. Mol. Biol. Rev., 1997, 61, 136-169. ‎[Crossref], [Google Scholar], [Publisher]

[11] J.R. Naglik, S.J. Challacombe, B. Hube, Candida albicans secreted aspartyl proteinases in virulence and pathogenesis, Microbiol. Mol. Biol. Rev., 2003, 67, 400-428. ‎[Crossref], [Google Scholar], [Publisher]

[12] C.A. Kumamoto, M.D. Vinces, Contributions of hyphae and hypha‐co‐regulated genes to Candida albicans virulence, Cell. Microbiol., 2005, 7, 1546-1554. ‎[Crossref], [Google Scholar], [Publisher]

[13] T. Wibawa, The role of virulence factors in Candida albicans pathogenicity, J. Med. Sci., 2016, 48, 58-68. ‎[Crossref], [Google Scholar], [Publisher]

[14] M. Schaller, C. Borelli, H.C. Korting, B. Hube, Hydrolytic enzymes as virulence factors of Candida albicans, Mycoses., 2005, 48, 365-377. ‎[Crossref], [Google Scholar], [Publisher]

[15] R.A. Calderone, W.A. Fonzi, Virulence factors of Candida albicans, Trends Microbiol., 2001, 9, 327-335. ‎[Crossref], [Google Scholar], [Publisher]

[16] M. Vilanova, L. Teixeira, Í. Caramalho, E. Torrado, A. Marques, P. Madureira, A. Ribeiro, P. Ferreira, M. Gama, J. Demengeot, Protection against systemic candidiasis in mice immunized with secreted aspartic proteinase 2, Immunology., 2004, 111, 334-42. ‎[Crossref], [Google Scholar], [Publisher]

[17] W.L. Chaffin, Candida albicans cell wall proteins, Microbiol. Mol. Biol. Rev., 2008, 72, 495-544. ‎[Crossref], [Google Scholar], [Publisher]

[18] D. Shi, Y. Zhao, H. Yan, H. Fu, Y. Shen, G. Lu, H. Mei, Y. Qiu, D. Li, W. Liu, Antifungal effects of undecylenic acid on the biofilm formation of Candida albicans, Int. J. Clin. Pharmacol. Ther., 2016, 54, 343-353. ‎[Crossref], [Google Scholar], [Publisher]

[19] X. Zhao, S.H. Oh, G. Cheng, C.B. Green, J.A. Nuessen, K. Yeater, R.P. Leng, A.J. Brown, L.L. Hoyer, ALS3 and ALS8 represent a single locus that encodes a Candida albicans adhesin; functional comparisons between Als3p and Als1p, Microbiology., 2004, 150, 2415-2428. ‎[Crossref], [Google Scholar], [Publisher]

[20] N. Tsuchimori, L.L. Sharkey, W.A. Fonzi, S.W. French, J.E. Edwards Jr, S.G. Filler, Reduced virulence of HWP1-deficient mutants of Candida albicans and their interactions with host cells, Infect. Immun., 2000, 68, 1997-2002. ‎[Crossref], [Google Scholar], [Publisher]

[21] K. Ishida, J.C.P. de Mello, D.A.G. Cortez, B.P.D. Filho, T. Ueda-Nakamura, C.V. Nakamura, Influence of tannins from Stryphnodendron adstringens on growth and virulence factors of Candida albicans. J. Antimicrob. Chemother., 2006, 58, 942-949. ‎[Crossref], [Google Scholar], [Publisher]

[22] R. Giordani, P. Regli, J. Kaloustian, C. Mikail, L. Abou, H. Portugal, Antifungal effect of various essential oils against Candidaalbicans. Potentiation of antifungal action of amphotericin B by essential oil from Thymus vulgaris, Phytother Res ., 2004, 18, 990-995. ‎[Crossref], [Google Scholar], [Publisher]

[23] G.G. Nascimento, J. Locatelli, P.C. Freitas, G.L. Silva, Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria, Braz. J. Microbiol., 2000, 31, 247-256. ‎[Crossref], [Google Scholar], [Publisher]

[24] S. Manandhar, S. Luitel, R.K. Dahal, In vitro antimicrobial activity of some medicinal plants against human pathogenic bacteria, J. Trop. Med., 2019, 2019. ‎[Crossref], [Google Scholar], [Publisher]

[25] I.B. Friis, Forests and forest trees of northeast tropical Africa: their natural habitats and distribution patterns in Ethiopia, Djibouti and Somalia. HMSO., 1992. [Google Scholar], [Publisher]

[26] M. Hall, S. Neale, T.M. Al‐Abbasi, A.G. Miller, Arabia's tallest trees: ecology, distribution and conservation status of the regionally endangered tree species Mimusops laurifolia, Nord. J. Bot., 2010, 28, 240-245. ‎[Crossref], [Google Scholar], [Publisher]

[27] A.K. Hegazy, A.A. Alatar, J. Thomas, M. Faisal, A.H. Alfarhan, K. Krzywinski, Compatibility and complementarity of indigenous and scientific knowledge of wild plants in the highlands of southwest Saudi Arabia, J. For. Res., 2014, 25, 437-444. ‎[Crossref], [Google Scholar], [Publisher]

[28] N.P. Sahu, K. Koike, Z. Jia, T. Nikaido, Novel triterpenoid saponins from Mimusops elengi, Tetrahedron., 1995, 51, 13435-46. ‎[Crossref], [Google Scholar], [Publisher]

[29] P.J. Shah, M.S. Gandhi, M.B. Shah, S.S. Goswami, D. Santani, Study of Mimusops elengi bark in experimental gastric ulcers, J Ethnopharmacol., 2003, 89, 305-11. ‎[Crossref], [Google Scholar], [Publisher]

[30] M. Padhi, S. Mahapatra, Evaluation of Antibacterial Potential of Leaf extracts of Mimusops elengi, Int. Res. J. Biol. Sci., 2013, 2, 46-49. [Google Scholar], [Publisher]

[31] H.M. Mostafa, M. Taha, A.O. El-Gendy, A.S. Khairalla, M. Abd El Fattah, M. Raslan, Antimicrobial and antivirulence saponins of Mimusops laurifolia leaves, Lett. Appl. Microbiol., 2023, 76, 19:ovad071. ‎[Crossref], [Google Scholar], [Publisher]

[32] M. Molla, N. Gemeda, S.M. Abay, Investigating potential modes of actions of Mimusops kummel fruit extract and solvent fractions for their antidiarrheal activities in mice, Evid. Based Complement. Altern. Med., 2017, 2017. ‎[Crossref], [Google Scholar], [Publisher]

[33] L.S. Chua, C.H. Lau, C.Y. Chew, D.A.S. Dawood, Solvent fractionation and acetone precipitation for crude saponins from Eurycoma longifolia extract, Molecules, 2019, 24, 1416. ‎[Crossref], [Google Scholar], [Publisher]

[34] B. Thalhamer, M. Himmelsbach, Characterization of quillaja bark extracts and evaluation of their purity using liquid chromatography high resolution mass spectrometry, Phytochem. Lett., 2014, 8, 97-100. ‎[Crossref], [Google Scholar], [Publisher]

[35] S. Theberge, A. Semlali, A. Alamri, K.P. Leung, M. Rouabhia, C. albicans growth, transition, biofilm formation, and gene expression modulation by antimicrobial decapeptide KSL-W, BMC Microbiol., 2013, 13, 246. ‎[Crossref], [Google Scholar], [Publisher]

[36] A. Semlali, K. Killer, H. Alanazi, W. Chmielewski, M. Rouabhia, Cigarette smoke condensate increases C. albicans adhesion, growth, biofilm formation, and EAP1, HWP1 and SAP2 gene expression, BMC Microbiol., 2014, 14, 1-9. ‎[Crossref], [Google Scholar], [Publisher]

[37] W. Gu, D. Guo, L. Zhang, D. Xu, S. Sun, The synergistic effect of azoles and fluoxetine against resistant Candida albicans strains is attributed to attenuating fungal virulence, Antimicrob. Agents Chemother., 2016, 60, 6179-6188. ‎[Crossref], [Google Scholar], [Publisher]

[38] M.M. Said, C. Watson, D. Grando, Garlic alters the expression of putative virulence factor genes SIR2 and ECE1 in vulvovaginal C. albicans isolates, Sci. Rep., 2020, 10, 3615. ‎[Crossref], [Google Scholar], [Publisher]

[39] H. Nailis, S. Kucharíková, M. Řičicová, P. Van Dijck, D. Deforce, H. Nelis, T. Coenye, Real-time PCR expression profiling of genes encoding potential virulence factors in Candida albicans biofilms: identification of model-dependent and-independent gene expression, BMC Microbiol., 2010, 10, 1-11. ‎[Crossref], [Google Scholar], [Publisher]

[40] H. Zhong, D.D. Hu, G.H. Hu, J. Su, S. Bi, Z.E. Zhang, Z. Wang, R.L. Zhang, Z. Xu, Y.Y. Jiang, Y. Wang, Activity of sanguinarine against Candida albicans biofilms, Antimicrob. Agents Chemother., 2017, 61, 10-1128. ‎[Crossref], [Google Scholar], [Publisher]

[41] G. Tronchin, M. Pihet, L.M. Lopes-Bezerra, J.P. Bouchara, Adherence mechanisms in human pathogenic fungi, Sabouraudia., 2008, 46, 749-772. ‎[Crossref], [Google Scholar], [Publisher]

[42] J. Irish, D.A. Carter, T. Shokohi, S.E. Blair, Honey has an antifungal effect against Candida species, Med. Mycol., 2006, 44, 289-291. ‎[Crossref], [Google Scholar], [Publisher]

[43] L. Chen, J. Yang, J. Yu, Z. Yao, L. Sun, Y. Shen, Q. Jin, VFDB: a reference database for bacterial virulence factors, Nucleic Acids Res., 2005, 33, D325-8. ‎[Crossref], [Google Scholar], [Publisher]

[44] L. Cegelski, G.R. Marshall, G.R. Eldridge, S.J. Hultgren, The biology and future prospects of antivirulence therapies, Nat. Rev. Microbiol., 2008, 6, 17-27. ‎[Crossref], [Google Scholar], [Publisher]

[45] C.F. Low, P.P. Chong, P.V.C. Yong, C.S.Y. Lim, Z. Ahmad, F. Othman, Inhibition of hyphae formation and SIR2 expression in Candida albicans treated with fresh Allium sativum (garlic) extract, J. Appl. Microbiol., 2008, 105, 2169-2177. ‎[Crossref], [Google Scholar], [Publisher]

[46] K. Gauwerky, C. Borelli, H.C. Korting, Targeting virulence: a new paradigm for antifungals, Drug Discov. Today., 2009,14, 214-222. ‎[Crossref], [Google Scholar], [Publisher]

[47] A. Bink, K. Pellens, B. PA Cammue, K. Thevissen, Anti-biofilm strategies: how to eradicate Candida biofilms?, The Open Mycology Journal, 2011, 5, 29-38. ‎[Crossref], [Google Scholar], [Publisher]

[48] M. Chevalier, A. Doglio, R. Rajendran, G. Ramage, I. Prêcheur, S. Ranque, Inhibition of adhesion‐specific genes by Solidago virgaurea extract causes loss of Candida albicans biofilm integrity, J. Appl. Microbiol., 2019, 127, 68-77. ‎[Crossref], [Google Scholar], [Publisher]

[49] L.J. McGaw, N. Lall, T.M. Hlokwe, A.L. Michel, J.J.M. Meyer, J.N. Eloff, Purified compounds and extracts from Euclea species with antimycobacterial activity against Mycobacterium bovis and fast-growing mycobacteria, Biol. Pharm. Bull., 2008, 31, 1429-1433. ‎[Crossref], [Google Scholar], [Publisher]

[50] A. Zida, S. Bamba, A. Yacouba, R. Ouedraogo-Traore, R.T. Guiguemdé, Anti-Candida albicans natural products, sources of new antifungal drugs: A review, J. Mycol. Med., 2017, 27, 1-19. ‎[Crossref], [Google Scholar], [Publisher]

[51] I. Friis, The taxonomy and distribution of Mimusops laurifolia (Sapotaceae), Kew Bulletin., 1980, 1, 785-792. ‎[Crossref], [Google Scholar], [Publisher]

[52] J. Eskander, C. Lavaud, S.M. Abdel-Khalik, H.S. Soliman, I.I. Mahmoud, C. Long, Saponins from the Leaves of Mimusops l aurifolia, J. Nat. Prod., 2005, 68, 832-841. ‎[Crossref], [Google Scholar], [Publisher]

[53] P. Koczurkiewicz, J. Czyż, I. Podolak, K. Wójcik, A. Galanty, Z. Janeczko, M. Michalik, Multidirectional effects of triterpene saponins on cancer cells-mini-review of in vitro studies, Acta Biochim. Pol., 2015, 62, 383-393. ‎[Pdf], [Google Scholar], [Publisher]

[54] M. Staniszewska, M. Bondaryk, K. Siennicka, J. Pilat, M. Schaller, W. Kurzatkowski, Role of aspartic proteinases in Candida albicans virulence. Part I. Substrate specifity of aspartic proteinases and Candida albicans pathogenesis, Postępy Mikrobiologii, 2012, 51, 127-135. ‎[Pdf], [Google Scholar], [Publisher]

[55] A.A. Kadry, A.M. El-Ganiny, A.M. El-Baz, Relationship between Sap prevalence and biofilm formation among resistant clinical isolates of Candida albicans, Afr. Health Sci., 2018, 18, 1166-1174. ‎[Crossref], [Google Scholar], [Publisher]

[56] L.L. Hoyer, E. Cota, Candida albicans agglutinin-like sequence (Als) family vignettes: a review of Als protein structure and function, Front Microbiol., 2016, 7, 280. ‎[Crossref], [Google Scholar], [Publisher]

[57] M. Patel, Z. Gulube, M. Dutton, The effect of Dodonaea viscosa var. angustifolia on Candida albicans proteinase and phospholipase production and adherence to oral epithelial cells, J. Ethnopharmacol., 2009, 124, 562-5. ‎[Crossref], [Google Scholar], [Publisher]

[58] L.S. Ramírez Aristizábal, S.M. Bonilla-Castañeda, J.A. Martínez-Acosta, Evaluation of antibacterial and antisap activities of the aerial part extracts of palicourea guianensis (RUBIACEAE), Pharmacology online, 2015, 3, 98-106. [Google Scholar], [Publisher]

Eurasian Chemical Communications

Saponins from Mimusops laurifolia target some key virulence factors in Candida albicans

References

References

Volume 5, Issue 10
October 2023
Pages 895-906

Saponins from Mimusops laurifolia target some key virulence factors in Candida albicans

References

References

Volume 5, Issue 10October 2023Pages 895-906

Volume 5, Issue 10
October 2023
Pages 895-906