C16-Fengycin A affect the growth of Candida albicans by destroying its cell wall and accumulating reactive oxygen species
Candida albicans is the most common clinical pathogenic fungus, which is highly susceptible to immunodeficiency. Development of novel antifungal agents has become a growing trend in the treatment of Candida infections. C16-Fengycin A, a lipopeptide isolated from Bacillus amyloliquefaciens fmb60 showed significant fungicidal activity against C. albicans. In the study, we explored the possible antifungal mode of C16-Fengycin A. It was predicted that C16-Fengycin A had the ability to disrupt the cell wall due to its alterations of cell ultrastructure, and reduction of cell wall hydrophobicity. This was further confirmed by the changes in the exposure of the cell wall components and down-regulation of the genes related in the cell wall synthesis. Meanwhile, with the treatment of C16-Fengycin A, the levels of reactive oxygen species (ROS) increased, resulting in mitochondrial dysfunction in the cells. We hypothesized that the antifungal mechanism of C16-Fengycin A might be via the destruction of the cell wall and the accumulation of ROS, which could activate the High-Osmolarity Glycerol Mitogen-Activated Protein Kinase (HOG-MAPK) pathway. Our findings indicated that C16-Fengycin A could be a potential antifungal agent that could be used to treat candida infections.
KeywordsAntifungal Candida albicans Cell wall ROS
This work was financially supported by grants from the National Natural Science Foundation of China (No. 31571887).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with animals performed by any of the authors.
- An AM, Francois IE, Meert EM, Li QT, Cammue BP, Thevissen K (2007) The antifungal activity of RsAFP2, a plant defensin from Raphanus sativus, involves the induction of reactive oxygen species in Candida albicans. J Mol Microbiol Biotechnol 13(4):243–247. https://doi.org/10.1159/000104753 CrossRefGoogle Scholar
- Arima K, Kakinuma A, Tamura G (1968) Surfactin, a crystalline peptidelipid surfactant produced by Bacillus subtilis: isolation, characterization and its inhibition of fibrin clot formation. Biochem Biophys Res Commun 31(3):488–494. https://doi.org/10.1016/0006-291X(68)90503-2 CrossRefPubMedPubMedCentralGoogle Scholar
- Bauer KD (1993) Quality control issues in DNA content flow cytometry. Ann N Y Acad Sci 677:59–77. https://doi.org/10.1111/j.1749-6632.1993.tb38765.x CrossRefPubMedGoogle Scholar
- Cheetham J, MacCallum DM, Doris KS, da Silva Dantas A, Scorfield S, Odds F, Smith DA, Quinn J (2011) MAPKKK-independent regulation of the Hog1 stress-activated protein kinase in Candida albicans. J Biol Chem 286(49):42002–42016. https://doi.org/10.1074/jbc.M111.265231 CrossRefPubMedPubMedCentralGoogle Scholar
- Fernandes C, Anjos J, Walker LA, Silva BM, Cortes L, Mota M, Munro CA, Gow NA, Gonçalves T (2014) Modulation of Alternaria infectoria cell wall chitin and glucan synthesis by cell wall synthase inhibitors. Antimicrob Agents Chemother 58(5):2894–2904. https://doi.org/10.1128/AAC.02647-13 CrossRefPubMedPubMedCentralGoogle Scholar
- Ford CB, Funt JM, Abbey D, Issi L, Guiducci C, Martinez DA, Delorey T, Li BY, White TC, Cuomo C, Rao RP, Berman J, Thompson DA, Regev A (2015) The evolution of drug resistance in clinical isolates of Candida albicans. Elife 4:e00662. https://doi.org/10.7554/eLife.00662 CrossRefPubMedPubMedCentralGoogle Scholar
- Gregori C, Schuller C, Roetzer A, Schwarzmuller T, Ammerer G, Kuchler K (2007) The high-osmolarity glycerol response pathway in the human fungal pathogen Candida glabrata strain ATCC 2001 lacks a signaling branch that operates in baker's yeast. Eukaryot Cell 6(9):1635–1645. https://doi.org/10.1128/EC.00106-07 CrossRefPubMedPubMedCentralGoogle Scholar
- Hultmark D, Engstrom Å, Bennich H, Kapur R, Boman HG (1982) Insect immunity: isolation and structure of cecropin D and four minor antibacterial components from Cecropia pupae. Eur J Biochem 127(1):207–217. https://doi.org/10.1111/j.1432-1033.1982.tb06857.x CrossRefGoogle Scholar
- Mandal SM, Porto WF, Dey P, Maiti MK, Ghosh AK, Franco OL (2013) The attack of the phytopathogens and the trumpet solo: identification of a novel plant antifungal peptide with distinct fold and disulfide bond pattern. Biochimie 95(10):1939–1948. https://doi.org/10.1016/j.biochi.2013.06.027 CrossRefPubMedGoogle Scholar
- Mouyna I, Fontaine T, Vai M, Monod M, Fonzi WA, Diaquin M, Popolo L, Hartland RP, Latge JP (2000) Glycosylphosphatidylinositol-anchored glucanosyltransferases play an active role in the biosynthesis of the fungal cell wall. J Biol Chem 275(20):14882–14889. https://doi.org/10.1074/jbc.275.20.14882 CrossRefPubMedGoogle Scholar
- Naito Y, Tohda H, Okuda K, Takazoe I (1993) Adherence and hydrophobicity of invasive and noninvasive strains of Porphyromonas gingivalis. Oral Microbiol Immunol 8(4):195–202. https://doi.org/10.1111/j.1399-302X.1993.tb00559.x CrossRefPubMedGoogle Scholar
- Qi X, Zhou C, Li P, Xu W, Cao Y, Ling H, Ning Chen W, Ming Li C, Xu R, Lamrani M, Mu Y, Leong SS, Wook Chang M, Chan-Park MB (2010) Novel short antibacterial and antifungal peptides with low cytotoxicity: efficacy and action mechanisms. Biochem Biophys Res Commun 398(3):594–600. https://doi.org/10.1016/j.bbrc.2010.06.131 CrossRefPubMedGoogle Scholar
- Sherrington SL, Sorsby E, Mahtey N, Kumwenda P, Lenardon MD, Brown I, Ballou ER, MacCallum DM, Hall RA (2017) Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition. PLoS Pathog 13(5):e1006403. https://doi.org/10.1371/journal.ppat.1006403 CrossRefPubMedPubMedCentralGoogle Scholar
- Sun L, Lu Z, Bie X, Lu F, Yang S (2006) Isolation and characterization of a co-producer of fengycins and surfactins, endophytic Bacillus amyloliquefaciens ES-2, from Scutellaria baicalensis Georgi. World J Microbiol Biotechnol 22(12):1259–1266. https://doi.org/10.1007/s11274-006-9170-0 CrossRefGoogle Scholar
- Yin H, Guo C, Wang Y, Liu D, Lv Y, Lv F, Lu Z (2013) Fengycin inhibits the growth of the human lung cancer cell line 95D through reactive oxygen species production and mitochondria-dependent apoptosis. Anti-Cancer Drugs 24(6):587–598. https://doi.org/10.1097/CAD.0b013e3283611395 CrossRefPubMedGoogle Scholar