Teasaponin induces reactive oxygen species-mediated mitochondrial dysfunction in Candida albicans

doi:10.5246/jcps.2021.11.077

Abstract

Abstract:

Candida albicans is the most prevalent commensal fungus and readily causes invasive fungal infection in immunocompromised individuals. Teasaponin (TS), a natural product generally regarded as safe, has been reported to inhibit filamentation of C. albicans. This study found that TS could exert moderate fungicidal activity against C. albicans, and the mode of action was further explored. The minimum fungicidal concentration (MFC) was determined by the broth microdilution method. The colony counting method was used to determine the time-killing curve of TS against C. albicans in every 2 h. The effect of TS on the content of intracellular reactive oxygen species (ROS) in C. albicans was analyzed by 2′,7′-dichlorofluorescin diacetate (DCFH-DA) staining, and the mitochondrial membrane potential (mtΔψ) was determined by rhodamine123 (RH123) staining. An ATP assay kit was utilized to determine the intracellular ATP levels after TS treatment. Results showed that TS-induced ROS accumulation and mitochondrial dysfunction contributed to the death of C. albicans cells. Further research demonstrated that VC could reinforce the fungicidal ability of TS. On the contrary, VE could antagonize the function of TS against C. albicans, which might guide the clinical application of TS. The results preliminarily elucidated the potential mechanisms of TS against C. albicans and might provide a potential option for the treatment of clinical Candida.

Key words: Candida albicans, Teasaponin, Fungicidal activity, Reactive oxygen species, Mitochondria

Supporting:

Shihui Li, Kemeng Guo, Nining Yin, Mingzhu Shan, Yao Zhu, Ying Li. Teasaponin induces reactive oxygen species-mediated mitochondrial dysfunction in Candida albicans[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(11): 895-903.

Figures/Tables 4

References 29

[1]	Fu, J.J.; Ding, Y.L.; Wei, B.; Wang, L.; Xu, S.L.; Qin, P.X.; Wei, L.H.; Jiang, L.J. Epidemiology of Candida albicans and non-C.albicans of neonatal candidemia at a tertiary care hospital in Western China. BMC Infect. Dis. 2017, 17, 329.
[2]	Mayer, F.L.; Wilson, D.; Hube, B. Candida albicans pathogenicity mechanisms. Virulence. 2013, 4, 119–128.
[3]	Lamoth, F.; Lockhart, S.R.; Berkow, E.L.; Calandra, T. Changes in the epidemiological landscape of invasive candidiasis. J. Antimicrob. Chemother. 2018, 73, i4–i13.
[4]	Pfaller, M.A.; Diekema, D.J.; Turnidge, J.D.; Castanheira, M.; Jones, R.N. Twenty years of the SENTRY antifungal surveillance program: results for candida species from 1997–2016. Open Forum Infet. Dis. 2019, 6, S79–S94.
[5]	Pfaller, M.A.; Moet, G.J.; Messer, S.A.; Jones, R.N.; Castanheira, M. Candida bloodstream infections: comparison of species distributions and antifungal resistance patterns in community-onset and nosocomial isolates in the SENTRY Antimicrobial Surveillance Program, 2008–2009. Antimicrob. Agents Chemother. 2011, 55, 561–566.
[6]	Sehu, M.M.; Sidjabat, H.; Ellis, D.; McCormack, J.; Geoffrey Playford, E.; Paterson, D.L. Emergence of novel mutations of caspofungin resistance in candida glabrata with prolonged therapy. Pathology. 2010, 42, S60.
[7]	Patridge, E.; Gareiss, P.; Kinch, M.S.; Hoyer, D. An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov. Today. 2016, 21, 204–207.
[8]	Tang, G.Y.; Meng, X.; Gan, R.Y.; Zhao, C.N.; Li, H.B. Health functions and related molecular mechanisms of tea components: an update review. Int. J. Mol. Sci. 2019, 20, 6196.
[9]	Li, J.; Zhang, A.Y.; Qi, Y.J.; Meng, X.C.; Zhang, Z.Q. Research progress in tea saponin from oil residue of camellia semiserrata. Food Sci. 2012, 33, 276–279.
[10]	Yang, X.P.; Jiang, X.D. Antifungal activity and mechanism of tea polyphenols against Rhizopus stolonifer. Biotechnol. Lett. 2015, 37, 1463–1472.
[11]	Khan, M.I.; Ahhmed, A.; Shin, J.H.; Baek, J.S.; Kim, M.Y.; Kim, J.D. Green tea seed isolated saponins exerts antibacterial effects against various strains of gram positive and gram negative bacteria, a comprehensive study in vitro and in vivo. Evid. Based Complementary Altern. Med. 2018, 2018, 3486106.
[12]	Li, E.; Sun, N.; Zhao, J.X.; Sun, Y.G.; Huang, J.G.; Lei, H.M.; Guo, J.H.; Hu, Y.L.; Wang, W.K.; Li, H.Q. In vitro evaluation of antiviral activity of tea seed saponins against porcine reproductive and respiratory syndrome virus. Antivir. Ther. 2015, 20, 743–752.
[13]	Rugera, S. Antipyretic and antinociceptive properties of the aqueous extract and Saponin from an edible vegetable: Vernonia amygdalina leaf. Afr. J. Food Agric. Nutr. Dev. 2013, 13, 7587–7606.
[14]	Sharangi Baran, A.B. Bioactive compounds and antioxidant properties of tea: status, global research and potentialities. J. Tea Sci. Res. 2016, 5, 1–13.
[15]	Li, Y.; Shan, M.; Li, S.; Wang, Y.; Yang, H.; Chen, Y.; Gu, B.; Zhu, Z. Teasaponin suppresses Candida albicans filamentation by reducing the level of intracellular cAMP. Ann. Transl. Med. 2020, 8, 175–187.
[16]	National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard. NCCLS. 2008, 28, 1–25.
[17]	Hadacek, F.; Greger, H. Testing of antifungal natural products: methodologies, comparability of results and assay choice. Phytochem. Anal. 2000, 11, 137–147.
[18]	Ding, X.R.; Yan, D.H.; Sun, W.; Zeng, Z.Y.; Su, R.R.; Su, J.R. Epidemiology and risk factors for nosocomial Non-Candida albicans candidemia in adult patients at a tertiary care hospital in North China. Med. Mycol. 2015, 53, 684–690.
[19]	Pristov, K.E.; Ghannoum, M.A. Resistance of Candida to azoles and echinocandins worldwide. Clin. Microbiol. Infect. 2019, 25, 792–798.
[20]	Dantas Ada, S.; Day, A.; Ikeh, M.; Kos, I.; Achan, B.; Quinn, J. Oxidative stress responses in the human fungal pathogen, Candida albicans. Biomolecules. 2015, 5, 142–165.
[21]	Mesa-Arango, A.C.; Trevijano-Contador, N.; Román, E.; Sánchez-Fresneda, R.; Casas, C.; Herrero, E.; Argüelles, J.C.; Pla, J.; Cuenca-Estrella, M.; Zaragoza, O. The production of reactive oxygen species is a universal action mechanism of Amphotericin B against pathogenic yeasts and contributes to the fungicidal effect of this drug. Antimicrob. Agents Chemother. 2014, 58, 6627–6638.
[22]	Leite, M.C.; Bezerra, A.P.; de Sousa, J.P.; Guerra, F.Q.; Lima Ede, O. Evaluation of antifungal activity and mechanism of action of citral against candida albicans. Evid. Based Complementary Altern. Med. 2014, 2014, 378280.
[23]	Li, W.R.; Shi, Q.S.; Dai, H.Q.; Liang, Q.; Xie, X.B.; Huang, X.M.; Zhao, G.Z.; Zhang, L.X. Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicans. Sci. Rep. 2016, 6, 22805.
[24]	Handy, D.E.; Loscalzo, J. Redox regulation of mitochondrial function. Antioxid. Redox Signal. 2012, 16, 1323–1367.
[25]	Villanueva, C.; Kross, R.D. Antioxidant-induced stress. Int. J. Mol. Sci. 2012, 13, 2091–2109.
[26]	Traber, M.G.; Stevens, J.F. Vitamins C and E: Beneficial effects from a mechanistic perspective. Free Radic. Biol. Med. 2011, 51, 1000–1013.
[27]	De Francesco, E.M.; Bonuccelli, G.; Maggiolini, M.; Sotgia, F.; Lisanti, M.P. Vitamin C and Doxycycline: a synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs). Oncotarget. 2017, 8, 67269–67286.
[28]	Bonuccelli, G.; De Francesco, E.M.; de Boer, R.; Tanowitz, H.B.; Lisanti, M.P. NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting "stemness". Oncotarget. 2017, 8, 20667–20678.
[29]	Ott, M.; Gogvadze, V.; Orrenius, S.; Zhivotovsky, B. Mitochondria, oxidative stress and cell death. Apoptosis. 2007, 12, 913–922.