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研究生:陳瑞青
研究生(外文):Chen, Ruei-Ching
論文名稱:探討人類抗菌胜肽hepcidin 25於白色念珠菌之作用機制
論文名稱(外文):Studying modes of action of human antimicrobial peptide hepcidin 25 against Candida albicans
指導教授:藍忠昱
指導教授(外文):Lan, Chung-Yu
口試委員:汪宏達高茂傑謝家慶陳穎練
口試委員(外文):Wang, Horng-DarKao, Mou-ChiehShieh, Jia-ChingChen, Ying-Lien
口試日期:2021-01-15
學位類別:博士
校院名稱:國立清華大學
系所名稱:分子與細胞生物研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2021
畢業學年度:109
語文別:英文
論文頁數:125
中文關鍵詞:白色念珠菌抗菌胜肽hepcidin 25
外文關鍵詞:Candida albicansantimicrobial peptidehepcidin 25
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人類Hepcidin 25 (hep 25) 是富含半胱胺酸由25個胺基酸組成的抗菌胜肽,並含有一個與銅/鎳金屬結合的ATCUN 模組 (motif)。本研究主要在於探討此胜肽對白色念珠菌之作用機制。在研究的第一部分,結果顯示hep 25 具有廣效的殺菌能力,可以有效對抗包含氟康唑耐藥性的白色念珠菌與其他念珠菌屬的臨床分離菌株,而且與抗壞血酸有協同殺菌作用。此外,ATCUN 模組不僅有助於活性氧類的產生,並且參與hep 25的殺菌力。另外,hep 25 會造成粒線體的活性氧類與鈣離子過度累積,降低粒線體膜電位。最後,hep 25也會造成半胱氨酸蛋白酶活化,細胞膜的磷脂醯絲氨酸外翻及DNA斷裂,這都顯示hep 25會誘導細胞凋亡。在第二部分的研究指出,hep 25 殺菌作用是具有能量依賴性的,而非透過破壞細胞膜的結構與改變細胞壁的完整性。使用細胞內吞作用抑制劑、內吞及其他缺陷之突變菌株等,進一步顯示內吞機制與銅離子分佈皆與hep 25的殺菌作用相關。本研究不僅有助於了解含有ATCUN 模組的抗菌胜肽,也提供未來開發此類抗真菌藥物之可能性。
Human hepcidin 25 (hep 25) is a 25-amino acid cysteine-rich antimicrobial peptide, and also contains the amino-terminal Cu(II)/Ni(II)-binding (ATCUN) motif. The main goal of this thesis is to study modes of action for hep 25 against Candida albicans. In the first part of this study, hep 25 was shown to have a broad-spectrum microbicidal activity against many strains including clinical isolates of fluconazole-resistant C. albicans and other Candida species, and possess a synergistic candidacidal activity with ascorbic acid. Moreover, the ATCUN motif of hep 25 not only involves in ROS production but also contributes to candidacidal activity of the peptide. Additionally, hep 25 causes mitochondrial reactive oxygen species (ROS) accumulation, calcium overload and decreased mitochondrial membrane potential. Finally, hep 25 induces many characteristics of apoptosis such as metacaspase activation, phosphatidylserine (PS) exposure and DNA fragmentation. In the second part of this study, the killing activity of hep25 is energy-dependent without membrane lytic activity and alteration of cell wall integrity. Using various endocytosis inhibitors and C. albicans mutant strains defective in endocytosis and other cellular processes, these results further indicated that endocytosis and copper distribution are associated with killing activity of hep 25. Together, this thesis reveals the mode of action for the ATCUN-containing peptides, and provides insights for future development of new antifungal agents.
中文摘要 I
Abstract II
致謝辭 III
Contents V
List of Tables X
List of Figures XI
Chapter 1 Introduction 1
1.1 The Candida species and Candida albicans 2
1.2 Antimicrobial peptides (AMPs) 3
1.3 Human hepcidin 5
1.3.2 Function of hep 25 8
1.3.2.1 Regulation of human iron homeostasis 8
1.3.2.2 Antimicrobial activity 9
1.3.2.3 DNA cleavage activity 10
1.4 Apoptosis 10
1.5 Clustered regularly interspaced short palindromic repeats (CRISPR) system for gene deletion in C. albicans 11
1.6 Aims of this study 12
Chapter 2 Materials and Methods 14
2.1 Peptides and regents 15
2.2 Strains and growth condition 15
2.3 Cell susceptibility to hep 25 16
2.3.1 Minimum fungicidal concentration (MFC) assay 16
2.3.2 CFU counting assay 17
2.3.3 Propidium iodide (PI) staining 17
2.4 Liposome calcein leakage assay 17
2.4.1 Preparation of SUVs mimicking cell membrane of C. albicans and containing calcein 18
2.4.2 Calcein leakage assay 18
2.5 Determination of subcellular localization of hep 25-GGK-FITC 19
2.6 Measurement of intracellular ROS accumulation 19
2.7 Measurement of mitochondrial membrane potential (ΔΨm) 19
2.8 Measurement of mitochondrial calcium level 20
2.9 Metacaspase activity assay 20
2.10 Annexin V-FITC and PI co-staining assay 21
2.11 Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay 21
2.12 Statistical analysis 22
Chapter 3 Results 23
Part I:Hep 25 induces Candida albicans apoptosis 24
3.1 Concentration and pH-dependent candidacidal activity of hep 25 25
3.2 Candidacidal activity of hep 25 in Candida clinical isolates 26
3.3 Hep 25 induces intracellular ROS accumulation 26
3.4 The ATCUN motif of hep 25 is involved in ROS production and correlated with the activity of hep 25 27
3.5 Hep 25 alters mitochondrial potential and calcium homeostasis 28
3.6 Mitochondrial metabolic state also affects cell susceptibility to hep 25 29
3.7 Hep 25 induces metacaspase activation 30
3.8 Hep 25 induces phosphatidylserine (PS) externalization and DNA fragmentation 31
Part II:Energy-dependent endocytosis is linked to the fungicidal activity of hep 25 against C. albicans 57
3.8 Hep 25 kills C. albicans without changing its cell wall and cell membrane integrity 58
3.10 The candidacidal activity of hep 25 is energy-dependent 59
3.11 Endocytosis process is correlated with the candidacidal activity of hep 25 60
3.12 Deletion of the low-affinity copper transporter Ctr2, but not the CTR1-null mutant, is supersensitive to hep 25 60
Chapter 4 Discussion and Future Perspectives 69
4.1 Part I: Hep 25 induces C. albicans cells apoptosis 70
4.1.1 The candidacidal activity of hep 25 70
4.1.2 The ATCUN motif and the candidacidal activity of hep 25 71
4.1.3 Mitochondrial ROS production is also related to the candidacidal activity of hep 25 72
4.1.4 Hep 25 causes mitochondrial dysfunction and apoptosis 73
4.2 Part II: Energy-dependent endocytosis is linked to the fungicidal activity of hep 25 against C. albicans 75
4.2.1 The association of hep 25 and C. albicans cell surface 75
4.2.2 Hep 25 gains entry into C. albicans cells through endocytosis 75
4.2.3 Copper homeostasis, intracellular trafficking and hep 25 76
4.3 Future perspectives 78
4.3.1 To assessment of the potential synergistic effects of hep 25 78
4.3.2 Modulation of candidacidal activity of hep 25 mediated by copper 79
4.3.3 To reveal the mechanisms of endocytosis and intracellular trafficking of hep 25 80
Chapter 5 References 93
Chapter 6 Additional studies: using the CRISPR/Cas9 system to generate the CTR1-null mutant 106
6. 1 The CRISPR system for C. albicans gene editing 107
6. 2 The detailed protocol for generation of C. albicans CTR1-null mutant 107
6.2.1 To generate the Cas9-sgCtr1RNA expression cassette (Step 1 in Figure 34) 107
6.2.2 Design of the repair template primers and generation of the repair template by overlap extension PCR (Step 2 in Figure 34) 108
6.2.3 Co-transformation of the Cas9-sgCTR1RNA and the repair template into C. albicans (Step 3 and 4 in Figure 34) 109
6.2.4 Validation of the correct insertion of the Cas9-sgCtr1RNA and the repair template in C. albicans genome (Step 5 in Figure 34) 110
6.2.5 Cassette pop-out through FLP-mediated homologous recombination and allele specific PCR (Step 6 and 7 in Figure 34) 112
6.2.6 Phenotypic characterization of CTR1-null mutant constructed using the CRISPR/CaCas9 system (Step 8 and 9 in Figure 34) 113
Appendix 125
(2011). An introduction to the medically important Candida species. In Candida and candidiasis, pp. 9-25.
(2012). Understanding how the yeast metacaspase Yca1 functions in apoptosis. Journal of Biological Chemistry 287, 29260-29260.
Abbas, I.M., Vranic, M., Hoffmann, H., El-Khatib, A.H., Montes-Bayón, M., Möller, H.M., and Weller, M.G. (2018). Investigations of the copper peptide hepcidin-25 by LC-MS/MS and NMR. International journal of molecular sciences 19.
Alanis, A.J. (2005). Resistance to antibiotics: are we in the post-antibiotic era? Archives of medical research 36, 697-705.
Alvarez, C.A., Guzmán, F., Cárdenas, C., Marshall, S.H., and Mercado, L. (2014). Antimicrobial activity of trout hepcidin. Fish & shellfish immunology 41, 93-101.
Amato, P., and Christner, B.C. (2009). Energy metabolism response to low-temperature and frozen conditions in Psychrobacter cryohalolentis. Applied and environmental microbiology 75, 711-718.
Ameisen, J.C. (1996). The origin of programmed cell death. Science (New York, NY) 272, 1278-1279.
Apodaca, G. (2001). Endocytic traffic in polarized epithelial cells: role of the actin and microtubule cytoskeleton. Traffic (Copenhagen, Denmark) 2, 149-159.
Ayscough, K.R., Stryker, J., Pokala, N., Sanders, M., Crews, P., and Drubin, D.G. (1997). High rates of actin filament turnover in budding yeast and roles for actin in establishment and maintenance of cell polarity revealed using the actin inhibitor latrunculin-A. The Journal of cell biology 137, 399-416.
Bahar, A.A., and Ren, D. (2013). Antimicrobial peptides. Pharmaceuticals (Basel, Switzerland) 6, 1543-1575.
Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D.A., and Horvath, P. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science (New York, NY) 315, 1709-1712.
Basso, V., Garcia, A., Tran, D.Q., Schaal, J.B., Tran, P., Ngole, D., Aqeel, Y., Tongaonkar, P., Ouellette, A.J., and Selsted, M.E. (2018). Fungicidal potency and mechanisms of θ-defensins against multidrug-resistant Candida species. Antimicrobial agents and chemotherapy 62.
Bechinger, B., and Lohner, K.J.B.e.B.A.-B. (2006). Detergent-like actions of linear amphipathic cationic antimicrobial peptides. 1758, 1529-1539.
Becker, B., and Schmitt, M.J. (2011). Adapting yeast as model to study ricin toxin a uptake and trafficking. Toxins 3, 834-847.
Boettner, D.R., Chi, R.J., and Lemmon, S.K. (2012). Lessons from yeast for clathrin-mediated endocytosis. Nature Cell Biology 14, 2-10.
Boparai, J.K., and Sharma, P.K. (2020). Mini review on antimicrobial peptides, sources, mechanism and recent applications. Protein and peptide letters 27, 4-16.
Borutaite, V. (2010). Mitochondria as decision-makers in cell death. Environmental and molecular mutagenesis 51, 406-416.
Carmona-Gutierrez, D., Eisenberg, T., Büttner, S., Meisinger, C., Kroemer, G., and Madeo, F. (2010). Apoptosis in yeast: triggers, pathways, subroutines. Cell death and differentiation 17, 763-773.
Carraro, M., and Bernardi, P. (2016). Calcium and reactive oxygen species in regulation of the mitochondrial permeability transition and of programmed cell death in yeast. Cell calcium 60, 102-107.
Chen, R.C., and Lan, C.Y. (2020). Human antimicrobial peptide hepcidin 25-induced apoptosis in Candida albicans. Microorganisms 8.
Choi, K.Y., Chow, L.N., and Mookherjee, N. (2012). Cationic host defence peptides: multifaceted role in immune modulation and inflammation. Journal of innate immunity 4, 361-370.
Chudzik, B., Koselski, M., Czuryło, A., Trębacz, K., and Gagoś, M. (2015). A new look at the antibiotic amphotericin B effect on Candida albicans plasma membrane permeability and cell viability functions. European Biophysics Journal 44, 77-90.
Conklin, S.E., Bridgman, E.C., Su, Q., Riggs-Gelasco, P., Haas, K.L., and Franz, K.J. (2017). Specific histidine residues confer histatin peptides with copper-dependent activity against Candida albicans. Biochemistry 56, 4244-4255.
Cornillon, S., Foa, C., Davoust, J., Buonavista, N., Gross, J.D., and Golstein, P. (1994). Programmed cell death in Dictyostelium. Journal of cell science 107 ( Pt 10), 2691-2704.
De Brucker, K., Cammue, B.P., and Thevissen, K. (2011). Apoptosis-inducing antifungal peptides and proteins. Biochemical Society transactions 39, 1527-1532.
De Domenico, I., Ward, D.M., Langelier, C., Vaughn, M.B., Nemeth, E., Sundquist, W.I., Ganz, T., Musci, G., and Kaplan, J. (2007). The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Molecular biology of the cell 18, 2569-2578.
Divyashree, M., Mani, M.K., Reddy, D., Kumavath, R., Ghosh, P., Azevedo, V., and Barh, D. (2020). Clinical applications of antimicrobial peptides (AMPs): Where do we stand now? Protein and peptide letters 27, 120-134.
Dutta, D., and Donaldson, J.G. (2012). Search for inhibitors of endocytosis: Intended specificity and unintended consequences. Cellular logistics 2, 203-208.
Edgerton, M., Koshlukova, S.E., Lo, T.E., Chrzan, B.G., Straubinger, R.M., and Raj, P.A. (1998). Candidacidal activity of salivary histatins. Identification of a histatin 5-binding protein on Candida albicans. The Journal of biological chemistry 273, 20438-20447.
Esmieu, C., Guettas, D., Conte-Daban, A., Sabater, L., Faller, P., and Hureau, C. (2019). Copper-targeting approaches in Alzheimer's disease: How to improve the fallouts obtained from in vitro studies. Inorganic chemistry 58, 13509-13527.
Estaquier, J., Vallette, F., Vayssiere, J.L., and Mignotte, B. (2012). The mitochondrial pathways of apoptosis. Advances in experimental medicine and biology 942, 157-183.
Fahrenkrog, B., Sauder, U., and Aebi, U. (2004). The S. cerevisiae HtrA-like protein Nma111p is a nuclear serine protease that mediates yeast apoptosis. Journal of cell science 117, 115-126.
Falcón-Pérez, J.M., Nazarian, R., Sabatti, C., and Dell'Angelica, E.C. (2005). Distribution and dynamics of Lamp1-containing endocytic organelles in fibroblasts deficient in BLOC-3. 118, 5243-5255.
Gazit, E., Boman, A., Boman, H.G., and Shai, Y. (1995). Interaction of the mammalian antibacterial peptide cecropin P1 with phospholipid vesicles. Biochemistry 34, 11479-11488.
Ghannoum, M.A., Jurevic, R.J., Mukherjee, P.K., Cui, F., Sikaroodi, M., Naqvi, A., and Gillevet, P.M. (2010). Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLOS Pathogens 6, e1000713.
Gillum, A.M., Tsay, E.Y., and Kirsch, D.R. (1984). Isolation of the Candida albicans gene for orotidine-5'-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Molecular & general genetics : MGG 198, 179-182.
Giorgi, C., Baldassari, F., Bononi, A., Bonora, M., De Marchi, E., Marchi, S., Missiroli, S., Patergnani, S., Rimessi, A., Suski, J.M., et al. (2012). Mitochondrial Ca2+ and apoptosis. Cell calcium 52, 36-43.
Giuliani, A., Pirri, G., Bozzi, A., Di Giulio, A., Aschi, M., and Rinaldi, A.C. (2008). Antimicrobial peptides: natural templates for synthetic membrane-active compounds. Cellular and Molecular Life Sciences 65, 2450-2460.
Gkouvatsos, K., Papanikolaou, G., and Pantopoulos, K. (2012). Regulation of iron transport and the role of transferrin. Biochimica et biophysica acta 1820, 188-202.
Gonzalez, P., Bossak, K., Stefaniak, E., Hureau, C., Raibaut, L., Bal, W., and Faller, P. (2018). N-terminal Cu-binding motifs (Xxx-Zzz-His, Xxx-His) and their derivatives: Chemistry, biology and medicinal applications. 24, 8029-8041.
Goode, B.L., Eskin, J.A., and Wendland, B. (2015a). Actin and endocytosis in budding yeast. Genetics 199, 315-358.
Goode, B.L., Eskin, J.A., and Wendland, B. (2015b). Actin and endocytosis in budding yeast. 199, 315-358.
Gudlaugsson, O., Gillespie, S., Lee, K., Vande Berg, J., Hu, J., Messer, S., Herwaldt, L., Pfaller, M., and Diekema, D. (2003). Attributable mortality of nosocomial candidemia, revisited. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 37, 1172-1177.
Guilloreau, L., Combalbert, S., Sournia-Saquet, A., Mazarguil, H., and Faller, P. (2007). Redox chemistry of copper-amyloid-beta: the generation of hydroxyl radical in the presence of ascorbate is linked to redox-potentials and aggregation state. Chembiochem : a European journal of chemical biology 8, 1317-1325.
Ha, Y.E., Peck, K.R., Joo, E.J., Kim, S.W., Jung, S.I., Chang, H.H., Park, K.H., and Han, S.H. (2012). Impact of first-line antifungal agents on the outcomes and costs of candidemia. Antimicrobial agents and chemotherapy 56, 3950-3956.
Hao, B., Cheng, S., Clancy, C.J., and Nguyen, M.H. (2013). Caspofungin kills Candida albicans by causing both cellular apoptosis and necrosis. Antimicrobial agents and chemotherapy 57, 326-332.
Hayes, B.M.E., Bleackley, M.R., Anderson, M.A., and van der Weerden, N.L. (2018). The plant defensin NaD1 enters the cytoplasm of Candida albicans via endocytosis. Journal of fungi (Basel, Switzerland) 4.
Helmerhorst, E.J., Troxler, R.F., and Oppenheim, F.G. (2001). The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species. Proceedings of the National Academy of Sciences of the United States of America 98, 14637-14642.
Hocquellet, A., le Senechal, C., and Garbay, B. (2012). Importance of the disulfide bridges in the antibacterial activity of human hepcidin. Peptides 36, 303-307.
Huang, H.W.J.B.e.B.A.-B. (2006). Molecular mechanism of antimicrobial peptides: the origin of cooperativity. 1758, 1292-1302.
Hunter, H.N., Fulton, D.B., Ganz, T., and Vogel, H.J. (2002). The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. The Journal of biological chemistry 277, 37597-37603.
Jang, W.S., Bajwa, J.S., Sun, J.N., and Edgerton, M. (2010). Salivary histatin 5 internalization by translocation, but not endocytosis, is required for fungicidal activity in Candida albicans. Molecular microbiology 77, 354-370.
Jansen, R., Embden, J.D., Gaastra, W., and Schouls, L.M. (2002). Identification of genes that are associated with DNA repeats in prokaryotes. Molecular microbiology 43, 1565-1575.
Jenssen, H., Hamill, P., and Hancock, R.E.W. (2006). Peptide antimicrobial agents. 19, 491-511.
Jordan, J.B., Poppe, L., Haniu, M., Arvedson, T., Syed, R., Li, V., Kohno, H., Kim, H., Schnier, P.D., Harvey, T.S., et al. (2009). Hepcidin revisited, disulfide connectivity, dynamics, and structure. The Journal of biological chemistry 284, 24155-24167.
Kang, X., Dong, F., Shi, C., Liu, S., Sun, J., Chen, J., Li, H., Xu, H., Lao, X., and Zheng, H. (2019). DRAMP 2.0, an updated data repository of antimicrobial peptides. Scientific data 6, 148.
Kemna, E.H., Tjalsma, H., Willems, H.L., and Swinkels, D.W. (2008). Hepcidin: from discovery to differential diagnosis. Haematologica 93, 90-97.
Klein, M., Swinnen, S., Thevelein, J.M., and Nevoigt, E. (2017). Glycerol metabolism and transport in yeast and fungi: established knowledge and ambiguities. Environmental microbiology 19, 878-893.
Krause, A., Neitz, S., Mägert, H.J., Schulz, A., Forssmann, W.G., Schulz-Knappe, P., and Adermann, K. (2000). LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS letters 480, 147-150.
Kulprachakarn, K., Chen, Y.L., Kong, X., Arno, M.C., Hider, R.C., Srichairatanakool, S., and Bansal, S.S. (2016). Copper(II) binding properties of hepcidin. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 21, 329-338.
Kuroda, K., Okumura, K., Isogai, H., and Isogai, E. (2015). The human cathelicidin antimicrobial peptide LL-37 and mimics are potential anticancer drugs. Frontiers in oncology 5, 144.
Kwolek-Mirek, M., and Zadrag-Tecza, R. (2014). Comparison of methods used for assessing the viability and vitality of yeast cells. FEMS yeast research 14, 1068-1079.
Laniado-Laborín, R., and Cabrales-Vargas, M.N. (2009). Amphotericin B: side effects and toxicity. Revista iberoamericana de micologia 26, 223-227.
Lau, J.L., and Dunn, M.K. (2018). Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorganic & Medicinal Chemistry 26, 2700-2707.
Laun, P., Pichova, A., Madeo, F., Fuchs, J., Ellinger, A., Kohlwein, S., Dawes, I., Fröhlich, K.U., and Breitenbach, M. (2001). Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. Molecular microbiology 39, 1166-1173.
Le, C.F., Fang, C.M., and Sekaran, S.D. (2017). Intracellular targeting mechanisms by antimicrobial peptides. Antimicrobial agents and chemotherapy 61.
Lee, C.C., Sun, Y., Qian, S., and Huang, H.W. (2011). Transmembrane pores formed by human antimicrobial peptide LL-37. Biophysical journal 100, 1688-1696.
Lee, J., Hwang, J.S., Hwang, I.S., Cho, J., Lee, E., Kim, Y., and Lee, D.G. (2012). Coprisin-induced antifungal effects in Candida albicans correlate with apoptotic mechanisms. Free radical biology & medicine 52, 2302-2311.
Lei, J., Sun, L., Huang, S., Zhu, C., Li, P., He, J., Mackey, V., Coy, D.H., and He, Q. (2019). The antimicrobial peptides and their potential clinical applications. American journal of translational research 11, 3919-3931.
Li, R., Zhang, R., Yang, Y., Wang, X., Yi, Y., Fan, P., Liu, Z., Chen, C., and Chang, J. (2018). CGA-N12, a peptide derived from chromogranin A, promotes apoptosis of Candida tropicalis by attenuating mitochondrial functions. The Biochemical journal 475, 1385-1396.
Li, X., Quan, C.-S., Yu, H.-Y., and Fan, S.-D. (2008). Multiple effects of a novel compound from Burkholderia cepacia against Candida albicans. FEMS Microbiology Letters 285, 250-256.
Libardo, M.D., Cervantes, J.L., Salazar, J.C., and Angeles-Boza, A.M. (2014). Improved bioactivity of antimicrobial peptides by addition of amino-terminal copper and nickel (ATCUN) binding motifs. ChemMedChem 9, 1892-1901.
Libardo, M.D., Nagella, S., Lugo, A., Pierce, S., and Angeles-Boza, A.M. (2015). Copper-binding tripeptide motif increases potency of the antimicrobial peptide Anoplin via reactive oxygen species generation. Biochemical and biophysical research communications 456, 446-451.
Lin, G.Y., Chang, C.F., and Lan, C.Y. (2020). The interaction between carbohydrates and the antimicrobial peptide P-113Tri is involved in the killing of Candida albicans. Microorganisms 8.
Lindsay, A.K., Deveau, A., Piispanen, A.E., and Hogan, D.A. (2012). Farnesol and cyclic AMP signaling effects on the hypha-to-yeast transition in Candida albicans. Eukaryot Cell 11, 1219-1225.
Liu, J., Sitaram, A., and Burd, C.G. (2007). Regulation of copper-dependent endocytosis and vacuolar degradation of the yeast copper transporter, Ctr1p, by the Rsp5 ubiquitin ligase. Traffic (Copenhagen, Denmark) 8, 1375-1384.
Lohner, K., and Blondelle, S.E. (2005). Molecular mechanisms of membrane perturbation by antimicrobial peptides and the use of biophysical studies in the design of novel peptide antibiotics. Combinatorial chemistry & high throughput screening 8, 241-256.
Lombardi, L., Maisetta, G., Batoni, G., and Tavanti, A. (2015). Insights into the antimicrobial properties of hepcidins: advantages and drawbacks as potential therapeutic agents. Molecules (Basel, Switzerland) 20, 6319-6341.
Lone, S.A., Wani, M.Y., Fru, P., and Ahmad, A. (2020). Cellular apoptosis and necrosis as therapeutic targets for novel eugenol tosylate congeners against Candida albicans. Scientific Reports 10.
Lu, R., Drubin, D.G., and Sun, Y. (2016). Clathrin-mediated endocytosis in budding yeast at a glance. 129, 1531-1536.
Madeo, F., Fröhlich, E., Ligr, M., Grey, M., Sigrist, S.J., Wolf, D.H., and Fröhlich, K.U. (1999). Oxygen stress: a regulator of apoptosis in yeast. The Journal of cell biology 145, 757-767.
Maisetta, G., Petruzzelli, R., Brancatisano, F.L., Esin, S., Vitali, A., Campa, M., and Batoni, G. (2010). Antimicrobial activity of human hepcidin 20 and 25 against clinically relevant bacterial strains: effect of copper and acidic pH. Peptides 31, 1995-2002.
Maisetta, G., Vitali, A., Scorciapino, M.A., Rinaldi, A.C., Petruzzelli, R., Brancatisano, F.L., Esin, S., Stringaro, A., Colone, M., Luzi, C., et al. (2013). pH-dependent disruption of Escherichia coli ATCC 25922 and model membranes by the human antimicrobial peptides hepcidin 20 and 25. The FEBS journal 280, 2842-2854.
Malyszko, J. (2009). Hepcidin assays: Ironing out some details. 4, 1015-1016.
Martin, L., van Meegern, A., Doemming, S., and Schuerholz, T. (2015). Antimicrobial peptides in human sepsis. Frontiers in immunology 6, 404.
Marvin, M.E., Williams, P.H., and Cashmore, A.M. (2003). The Candida albicans CTR1 gene encodes a functional copper transporter. Microbiology (Reading, England) 149, 1461-1474.
Matteoni, R., and Kreis, T.E. (1987). Translocation and clustering of endosomes and lysosomes depends on microtubules. Journal of Cell Biology 105, 1253-1265.
McElroy, G.S., and Chandel, N.S. (2019). Probing mitochondrial metabolism in vivo. 116, 20-22.
McManus, B.A., and Coleman, D.C. (2014). Molecular epidemiology, phylogeny and evolution of Candida albicans. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 21, 166-178.
MEJÍA-ARGUETA, E.L., SANTILLÁN-BENÍTEZ, J.G., and ORTIZ-REYNOSO, M. (2020). Antimicrobial peptides, an alternative to combat bacterial reisstance. Acta Biológica Colombiana. 25, 294-302.
Melino, S., Garlando, L., Patamia, M., Paci, M., and Petruzzelli, R. (2005). A metal-binding site is present in the amino terminal region of the bioactive iron regulator hepcidin-25. 66, 65-71.
Melino, S., Santone, C., Di Nardo, P., and Sarkar, B. (2014). Histatins: salivary peptides with copper(II)- and zinc(II)-binding motifs: perspectives for biomedical applications. The FEBS journal 281, 657-672.
Mihajlovic, M., and Lazaridis, T. (2010). Antimicrobial peptides bind more strongly to membrane pores. Biochimica et biophysica acta 1798, 1494-1502.
Mochon, A.B., and Liu, H. (2008). The antimicrobial peptide histatin-5 causes a spatially restricted disruption on the Candida albicans surface, allowing rapid entry of the peptide into the cytoplasm. PLOS Pathogens 4, e1000190.
Mojica, F.J., Díez-Villaseñor, C., García-Martínez, J., and Soria, E. (2005). Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. Journal of molecular evolution 60, 174-182.
Morio, F., Lombardi, L., and Butler, G. (2020). The CRISPR toolbox in medical mycology: State of the art and perspectives. PLoS Pathog 16, e1008201.
Nami, S., Aghebati-Maleki, A., Morovati, H., and Aghebati-Maleki, L. (2019). Current antifungal drugs and immunotherapeutic approaches as promising strategies to treatment of fungal diseases. Biomedicine & pharmacotherapy 110, 857-868.
Nemeth, E., and Ganz, T. (2009). The role of hepcidin in iron metabolism. Acta haematologica 122, 78-86.
Nemeth, E., Preza, G.C., Jung, C.L., Kaplan, J., Waring, A.J., and Ganz, T. (2006). The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood 107, 328-333.
Noble, S.M., French, S., Kohn, L.A., Chen, V., and Johnson, A.D. (2010a). Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nature Genetics 42, 590-598.
Noble, S.M., French, S., Kohn, L.A., Chen, V., and Johnson, A.D. (2010b). Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nat Genet 42, 590-598.
Pantopoulos, K. (2018). Inherited disorders of iron overload. Frontiers in nutrition 5, 103.
Park, C.H., Valore, E.V., Waring, A.J., and Ganz, T. (2001). Hepcidin, a urinary antimicrobial peptide synthesized in the liver. The Journal of biological chemistry 276, 7806-7810.
Perrone, G.G., Tan, S.X., and Dawes, I.W. (2008). Reactive oxygen species and yeast apoptosis. Biochimica et biophysica acta 1783, 1354-1368.
Phaniendra, A., Jestadi, D.B., and Periyasamy, L. (2015). Free radicals: properties, sources, targets, and their implication in various diseases. Indian journal of clinical biochemistry : IJCB 30, 11-26.
Phillips, A.J., Sudbery, I., and Ramsdale, M. (2003). Apoptosis induced by environmental stresses and amphotericin B in Candida albicans. Proceedings of the National Academy of Sciences of the United States of America 100, 14327-14332.
Pickar-Oliver, A., and Gersbach, C.A. (2019). The next generation of CRISPR-Cas technologies and applications. Nature reviews Molecular cell biology 20, 490-507.
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., and Loréal, O. (2001). A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. The Journal of biological chemistry 276, 7811-7819.
Pizzolato-Cezar, L.R., Okuda-Shinagawa, N.M., and Machini, M.T. (2019). Combinatory therapy antimicrobial peptide-antibiotic to minimize the ongoing rise of resistance. Frontiers in microbiology 10, 1703.
Portnoy, M., Schmidt, P., Rogers, R., and Culotta, V. (2001). Metal transporters that contribute copper to metallochaperones in Saccharomyces cerevisiae. Molecular Genetics and Genomics 265, 873-882.
Pradelli, L.A., Bénéteau, M., and Ricci, J.E. (2010). Mitochondrial control of caspase-dependent and -independent cell death. Cellular and molecular life sciences : CMLS 67, 1589-1597.
Prestinaci, F., Pezzotti, P., and Pantosti, A. (2015). Antimicrobial resistance: a global multifaceted phenomenon. Pathogens and global health 109, 309-318.
Preza, G.C., Pinon, R., Ganz, T., and Nemeth, E. (2011). The metabolic fate of the peptide hormone hepcidin. 25, 1119.1113-1119.1113.
Puri, S., and Edgerton, M. (2014). How does it kill?: understanding the candidacidal mechanism of salivary histatin 5. Eukaryot Cell 13, 958-964.
Ram, A.F., and Klis, F.M. (2006). Identification of fungal cell wall mutants using susceptibility assays based on calcofluor white and congo red. Nature protocols 1, 2253-2256.
Rappoport, J.Z., and Simon, S.M. (2008). A functional GFP fusion for imaging clathrin-mediated endocytosis. Traffic (Copenhagen, Denmark) 9, 1250-1255.
Rautenbach, M., Troskie, A.M., and Vosloo, J.A. (2016). Antifungal peptides: To be or not to be membrane active. Biochimie 130, 132-145.
Rees, E.M., Lee, J., and Thiele, D.J. (2004). Mobilization of intracellular copper stores by the ctr2 vacuolar copper transporter. The Journal of biological chemistry 279, 54221-54229.
Ross, S.L., Tran, L., Winters, A., Lee, K.J., Plewa, C., Foltz, I., King, C., Miranda, L.P., Allen, J., Beckman, H., et al. (2012). Molecular mechanism of hepcidin-mediated ferroportin internalization requires ferroportin lysines, not tyrosines or JAK-STAT. Cell metabolism 15, 905-917.
Sankararamakrishnan, R., Verma, S., and Kumar, S. (2005). ATCUN-like metal-binding motifs in proteins: identification and characterization by crystal structure and sequence analysis. Proteins 58, 211-221.
Sasse, C., and Morschhäuser, J. (2012). Gene deletion in Candida albicans wild-type strains using the SAT1-flipping strategy. Methods in molecular biology (Clifton, NJ) 845, 3-17.
Sendzik, M., Pushie, M.J., Stefaniak, E., and Haas, K.L. (2017). Structure and affinity of Cu(I) bound to human serum albumin. Inorganic chemistry 56, 15057-15065.
Sengupta, D., Leontiadou, H., Mark, A.E., and Marrink, S.-J. (2008). Toroidal pores formed by antimicrobial peptides show significant disorder. Biochimica et Biophysica Acta (BBA) - Biomembranes 1778, 2308-2317.
Sheu, S.-S., Nauduri, D., and Anders, M.W. (2006). Targeting antioxidants to mitochondria: A new therapeutic direction. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1762, 256-265.
Singh, R., Letai, A., and Sarosiek, K. (2019). Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nature reviews Molecular cell biology 20, 175-193.
Tan, B.H., Chakrabarti, A., Li, R.Y., Patel, A.K., Watcharananan, S.P., Liu, Z., Chindamporn, A., Tan, A.L., Sun, P.L., Wu, U.I., et al. (2015). Incidence and species distribution of candidaemia in Asia: a laboratory-based surveillance study. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 21, 946-953.
Tay, W.M., Hanafy, A.I., Angerhofer, A., and Ming, L.-J. (2009). A plausible role of salivary copper in antimicrobial activity of histatin-5—Metal binding and oxidative activity of its copper complex. Bioorganic & Medicinal Chemistry Letters 19, 6709-6712.
Thakre, A., Jadhav, V., Kazi, R., Shelar, A., Patil, R., Kharat, K., Zore, G., and Karuppayil, S.M. (2020). Oxidative stress induced by piperine leads to apoptosis in Candida albicans. Medical Mycology.
Tsai, P.W., Yang, C.Y., Chang, H.T., and Lan, C.Y. (2011). Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates. PloS one 6, e17755.
Tselepis, C., Ford, S.J., McKie, A.T., Vogel, W., Zoller, H., Simpson, R.J., Diaz Castro, J., Iqbal, T.H., and Ward, D.G. (2010). Characterization of the transition-metal-binding properties of hepcidin. The Biochemical journal 427, 289-296.
Underhill, D.M., and Iliev, I.D. (2014). The mycobiota: interactions between commensal fungi and the host immune system. Nature Reviews Immunology 14, 405-416.
van den Bogaart, G., Guzmán, J.V., Mika, J.T., and Poolman, B. (2008). On the mechanism of pore formation by melittin. The Journal of biological chemistry 283, 33854-33857.
Vestergaard, G., Garrett, R.A., and Shah, S.A. (2014). CRISPR adaptive immune systems of Archaea. RNA biology 11, 156-167.
Volonte, D., Galbiati, F., and Lisanti, M.P. (1999). Visualization of caveolin-1, a caveolar marker protein, in living cells using green fluorescent protein (GFP) chimeras. The subcellular distribution of caveolin-1 is modulated by cell-cell contact. FEBS letters 445, 431-439.
Vyas, V.K., Barrasa, M.I., and Fink, G.R. (2015). A Candida albicans CRISPR system permits genetic engineering of essential genes and gene families. Science advances 1, e1500248.
Vyas, V.K., Bushkin, G.G., Bernstein, D.A., Getz, M.A., Sewastianik, M., Barrasa, M.I., Bartel, D.P., and Fink, G.R. (2018). New CRISPR mutagenesis strategies reveal variation in repair mechanisms among fungi. mSphere 3.
Walter, D., Wissing, S., Madeo, F., and Fahrenkrog, B. (2006). The inhibitor-of-apoptosis protein Bir1p protects against apoptosis in S. cerevisiae and is a substrate for the yeast homologue of Omi/HtrA2. Journal of cell science 119, 1843-1851.
Wang, J., Dou, X., Song, J., Lyu, Y., Zhu, X., Xu, L., Li, W., and Shan, A. (2019). Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era. Medicinal research reviews 39, 831-859.
Wang, K., Dang, W., Xie, J., Zhu, R., Sun, M., Jia, F., Zhao, Y., An, X., Qiu, S., Li, X., et al. (2015). Antimicrobial peptide protonectin disturbs the membrane integrity and induces ROS production in yeast cells. Biochimica et Biophysica Acta (BBA) - Biomembranes 1848, 2365-2373.
Wisplinghoff, H., Bischoff, T., Tallent, S.M., Seifert, H., Wenzel, R.P., and Edmond, M.B. (2004). Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 39, 309-317.
Yang, L., Harroun, T.A., Weiss, T.M., Ding, L., and Huang, H.W. (2001). Barrel-stave model or toroidal model? A case study on melittin pores. Biophysical journal 81, 1475-1485.
Yang, M., Du, K., Hou, Y., Xie, S., Dong, Y., Li, D., and Du, Y. (2019). Synergistic antifungal effect of amphotericin B-loaded poly(lactic-co-glycolic acid) nanoparticles and ultrasound against Candida albicans biofilms. Antimicrobial agents and chemotherapy 63.
Yu, G., Baeder, D.Y., Regoes, R.R., and Rolff, J. (2016). Combination effects of antimicrobial peptides. Antimicrobial agents and chemotherapy 60, 1717-1724.
Zaoutis, T.E., Argon, J., Chu, J., Berlin, J.A., Walsh, T.J., and Feudtner, C. (2005). The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: A propensity analysis. Clinical Infectious Diseases 41, 1232-1239.
Zaritsky, J., Young, B., Wang, H.J., Westerman, M., Olbina, G., Nemeth, E., Ganz, T., Rivera, S., Nissenson, A.R., and Salusky, I.B. (2009). Hepcidin--a potential novel biomarker for iron status in chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN 4, 1051-1056.
Zerial, M., and McBride, H. (2001). Rab proteins as membrane organizers. Nature Reviews Molecular Cell Biology 2, 107-117.
Zharkova, M.S., Orlov, D.S., Golubeva, O.Y., Chakchir, O.B., Eliseev, I.E., Grinchuk, T.M., and Shamova, O.V. (2019). Application of antimicrobial peptides of the innate immune system in combination with conventional antibiotics-A novel way to combat antibiotic resistance? Frontiers in cellular and infection microbiology 9, 128.
Zheng, B., Wu, J.N., Schober, W., Lewis, D.E., and Vida, T. (1998). Isolation of yeast mutants defective for localization of vacuolar vital dyes. Proceedings of the National Academy of Sciences of the United States of America 95, 11721-11726.
Zorova, L.D., Popkov, V.A., Plotnikov, E.Y., Silachev, D.N., Pevzner, I.B., Jankauskas, S.S., Babenko, V.A., Zorov, S.D., Balakireva, A.V., Juhaszova, M., et al. (2018). Mitochondrial membrane potential. Analytical Biochemistry 552, 50-59.
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