Abstract
There is a need for new anti–Candida albicans (C. albicans) drugs owing to the emergence of drug resistance in recent years. AMP-17, an antimicrobial peptide from Musca domestica (M. domestica), is known to be an effective inhibitor of many fungal pathogens, including C. albicans. In this study, we investigated the potential mechanism underlying the anti–C. albicans effects of AMP-17 using flow cytometry, transmission electron microscopy, fluorescent probes, fluorescence microplate reader, and confocal laser microscopy. Transmission electron microscopy showed that, following AMP-17 treatment, the shape of C. albicans cells became irregular, and vacuoles could be seen in the cytoplasm. Furthermore, AMP-17 treatment resulted in an increase in reactive oxygen species (ROS) levels, depolarization of the mitochondrial membrane potential (MMP), and changes in the cell cycle, leading to the apoptosis and necrosis, which ultimately contributed to the death of C. albicans cells.
Similar content being viewed by others
References
Boniche C, Rossi SA, Kischkel B, Barbalho FV, Moura ANDA, Nosanchuk JD, Travassos LR, Taborda CP (2020) Immunotherapy against systemic fungal infections based on monoclonal antibodies. J Fungi 6:31. https://doi.org/10.3390/jof6010031
Chang W, Wu X, Cheng A, Zhang L, Ji M, Lou H (2011) Retigeric acid B exerts antifungal effect through enhanced reactive oxygen species and decreased cAMP. Biochimica et Biophysica Acta (BBA)-General Subjects 1810: 569-576. 569-576. https://doi.org/10.1016/j.bbagen.2011.02.001
Costa-de-Oliveira S, Rodrigues AG (2020) Candida albicans antifungal resistance and tolerance in bloodstream infections: the triad yeast-host-antifungal. Microorganisms 8:154. https://doi.org/10.3390/microorganisms8020154
Curtin JF, Donovan M, Cotter TG (2002) Regulation and measurement of oxidative stress in apoptosis. J Immunol Methods 265:49–72. https://doi.org/10.1016/S0022-1759(02)00070-4
Ding Y, Li Z, Li Y, Lu C, Wang H, Shen Y, Du L (2016) HSAF-induced antifungal effects in Candida albicans through ROS-mediated apoptosis. RSC Adv 6:30895–30904. https://doi.org/10.1039/c5ra26092b
Eisenberg T, Büttner S, Kroemer G, Madeo F (2007) The mitochondrial pathway in yeast apoptosis. Apoptosis 12:1011–1023. https://doi.org/10.1007/s10495-007-0758-0
Falanga A, Lombardi L, Franci G, Vitiello M, Iovene MR, Morelli G, Galdiero M, Galdiero S (2016) Marine antimicrobial peptides: nature provides templates for the design of novel compounds against pathogenic bacteria. Int J Mol Sci 17:785. https://doi.org/10.3390/ijms17050785
Golstein P, Aubry L, Levraud J (2003) Cell-death alternative model organisms: why and which? Nat Rev Mol Cell Biol 4:798–807. https://doi.org/10.1038/nrm1224
Gremillion KJ, Piperno DR (2009) Human behavioral ecology, phenotypic (developmental) plasticity, and agricultural origins: insights from the emerging evolutionary synthesis. Curr Anthropol 50:615–619. https://doi.org/10.1086/605360
Guo G, Tao R, Li Y, Ma H, Xiu J, Fu P, Wu J (2017) Identification and characterization of a novel antimicrobial protein from the housefly Musca domestica. Biochem Biophys Res Commun 490:746–752. https://doi.org/10.1016/j.bbrc.2017.06.112
Haque F, Verma NK, Alfatah M, Bijlani S, Bhattacharyya MS (2019) Sophorolipid exhibits antifungal activity by ROS mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways in Candida albicans. RSC Adv 9:41639–41648. https://doi.org/10.1039/c9ra07599b
Hou L, Shi Y, Zhai P, Le G (2007) Antibacterial activity and in vitro anti-tumor activity of the extract of the larvae of the housefly (Musca domestica). J Ethnopharmacol 111:227–231. https://doi.org/10.1016/j.jep.2006.11.015
Hwang B, Hwang J, Lee J, Kim J, Kim SR, Kim Y, Lee DG (2011) Induction of yeast apoptosis by an antimicrobial peptide, Papiliocin. Biochem Biophys Res Commun 408:89–93. https://doi.org/10.1016/j.bbrc.2011.03.125
Jamieson DJ (1998) Oxidative stress responses of the yeast Saccharomyces cerevisiae. Yeast 14:1511–1527. https://doi.org/10.1002/(SICI)1097-0061(199812)14:16<1511::AID-YEA356>3.0.CO;2-S
Jia C, Zhang J, Yu L, Wang C, Yang Y, Rong X, Xu K, Chu M (2019) Antifungal activity of coumarin against Candida albicans is related to apoptosis. Front Cell Infect Microbiol 8:445. https://doi.org/10.3389/fcimb.2018.00445
Jiangfan X, Tao W, Yu W, Jianwei W, Guo G, Yingchun Z, Xiaoli S (2016) Histological observation and expression patterns of antimicrobial peptides during fungal infection in Musca domestica (Diptera: Muscidae) Larvae. Braz Arch Biol Technol 59:e16160147. https://doi.org/10.1590/1678-4324-2016160147
Kounatidis I, Ligoxygakis P (2012) Drosophila as a model system to unravel the layers of innate immunity to infection. Open Biol 2:120075. https://doi.org/10.1098/rsob.120075
Kwun MS, Lee HJ, Lee DG (2021) β-amyrin-induced apoptosis in Candida albicans triggered by calcium. Fungal Biol 125:630–636. https://doi.org/10.1016/j.funbio.2021.03.006
Lan Y, Ye Y, Kozlowska J, Lam JK, Drake AF, Mason AJ (2010) Structural contributions to the intracellular targeting strategies of antimicrobial peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes 1798: 1934-1943. https://doi.org/10.1016/j.bbamem.2010.07.003
Lass-Flörl C, Samardzic E, Knoll M (2021) Serology anno 2021-fungal infections: from invasive to chronic. Clin Microbiol Infect 27:1230–1241. https://doi.org/10.1016/j.cmi.2021.02.005
Li Y, Chang W, Zhang M, Li X, Jiao Y, Lou H (2015) Diorcinol D exerts fungicidal action against Candida albicans through cytoplasm membrane destruction and ROS accumulation. PLoS One 10:e01286936. https://doi.org/10.1371/journal.pone.0128693
Ma H, Zhao X, Yang L, Su P, Fu P, Peng J, Yang N, Guo G (2020) Antimicrobial peptide AMP-17 affects Candida albicans by disrupting its cell wall and cell membrane integrity. Infect Drug Resist 13:2509. https://doi.org/10.2147/IDR.S250278
Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148:1145–1159. https://doi.org/10.1016/j.cell.2012.02.035
Pereira C, Silva RD, Saraiva L, Johansson B, Sousa MJ, Corte-Real M (2008) Mitochondria-dependent apoptosis in yeast. Biochimica et Biophysica Acta (BBA)-Molecular. Cell Res 1783:1286–1302. https://doi.org/10.1016/j.bbamcr.2008.03.010
Rockenfeller P, Madeo F (2008) Apoptotic death of ageing yeast. Exp Gerontol 43:876–881. https://doi.org/10.1016/j.exger.2008.08.044
Sharon A, Finkelstein A, Shlezinger N, Hatam I (2009) Fungal apoptosis: function, genes and gene function. FEMS Microbiol Rev 33:833–854. https://doi.org/10.1111/j.1574-6976.2009.00180.x
Sheehan G, Garvey A, Croke M, Kavanagh K (2018) Innate humoral immune defences in mammals and insects: the same, with differences ? Virulence 9:1625–1639. https://doi.org/10.1080/21505594.2018.1526531
Singh A, Sharma S, Khuller GK (2007) cAMP regulates vegetative growth and cell cycle in Candida albicans. Mol Cell Biochem 304:331–341. https://doi.org/10.1007/s11010-007-9516-4
Tan CT, Xu X, Qiao Y, Wang Y (2021) A peptidoglycan storm caused by β-lactam antibiotic's action on host microbiota drives Candida albicans infection. Nat Commun 12:1–13. https://doi.org/10.1038/s41467-021-22845-2
Terman A, Gustafsson B, Brunk UT (2006) The lysosomal-mitochondrial axis theory of postmitotic aging and cell death. Chem Biol Interact 163:29–37. https://doi.org/10.1016/j.cbi.2006.04.013
Tong Y, Zhang J, Sun N, Wang X, Wei Q, Zhang Y, Huang R, Pu Y, Dai H, Ren B (2021a) Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p. Sci Bull 66:1895–1905. https://doi.org/10.1016/j.scib.2020.12.035
Tong Y, Zhang J, Wang L, Wang Q, Huang H, Chen X, Zhang Q, Li H, Sun N, Liu G (2021b) Hyper-synergistic antifungal activity of rapamycin and peptide-like compounds against Candida albicans orthogonally via Tor1 kinase. ACS Infect Dis 7:2826–2835. https://doi.org/10.1021/acsinfecdis.1c00448
von der Haar T, Leadsham JE, Sauvadet A, Tarrant D, Adam IS, Saromi K, Laun P, Rinnerthaler M, Breitenbach-Koller H, Breitenbach M (2017) The control of translational accuracy is a determinant of healthy ageing in yeast. Open Biol 7:160291. https://doi.org/10.1098/rsob.160291
Wang X, Mohammad IS, Fan L, Zhao Z, Nurunnabi M, Sallam MA, Wu J, Chen Z, Yin L, He W (2021) Delivery strategies of amphotericin B for invasive fungal infections. Acta Pharm Sin B 11:2585–2604. https://doi.org/10.1016/j.apsb.2021.04.010
Wiederhold NP (2017) Antifungal resistance: current trends and future strategies to combat. Infect Drug Resist 10:249–259. https://doi.org/10.2147/IDR.S124918
Wubulikasimu A, Huang Y, Wali A, Yili A, Rong M (2020) A designed antifungal peptide with therapeutic potential for clinical drug-resistant Candida albicans. Biochem Biophys Res Commun 533:404–409. https://doi.org/10.1016/j.bbrc.2020.08.117
Yang L, Guo G, Tian Z, Zhou L, Zhu L, Peng J, Sun C, Huang M (2022) TMT-based quantitative proteomic analysis of the effects of novel antimicrobial peptide AMP-17 against Candida albicans. J Proteome 250:104385. https://doi.org/10.1016/j.jprot.2021.104385
Funding
This study was supported by the National Natural Science Foundation of China (grant numbers:81760647, 82060381), Science and Technology Planning Project of Guizhou Province (ZK [2022] general project 345), and Excellent Young Teacher Training Program of Sanquan College of Xinxiang Medical University (SQ2022YQJH01).
Author information
Authors and Affiliations
Contributions
HM, JP, and GG conceived and designed the experiments. HM, LY, ZT, and LZ performed the experiments. HM, JP, JX, and PF analyzed the data. JP and LY contributed reagents/materials/analysis tools. HM and GG wrote the paper. All authors read and approved the final manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Ma, H., Yang, L., Tian, Z. et al. Antimicrobial peptide AMP-17 exerts anti–Candida albicans effects through ROS-mediated apoptosis and necrosis. Int Microbiol 26, 81–90 (2023). https://doi.org/10.1007/s10123-022-00274-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10123-022-00274-5