CGA-N12, a peptide derived from chromogranin A, promotes apoptosis of <i>Candida tropicalis</i> by attenuating mitochondrial functions

Li, Ruifang; Zhang, Ruiling; Yang, Yanhui; Wang, Xueqin; Yi, Yanjie; Fan, Pei; Liu, Zhengwei; Chen, Chen; Chang, Junpeng

doi:10.1042/bcj20170894

Cited by 18 publications

(16 citation statements)

References 53 publications

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“…Because ROS are associated with yeast apoptosis in many cases [80], it was interested in determining whether hep 25 induces C. albicans cell death via apoptosis. In the early phase of apoptosis, the opening of the permeability transition pore causes mitochondrial dysfunction, losses of ∆Ψm and releases of apoptogenic factors into the cytosol [81,82]. Moreover, metacaspases are involved in the apoptotic cascade [83,84].…”

Section: Discussionmentioning

confidence: 99%

Human Antimicrobial Peptide Hepcidin 25-Induced Apoptosis in Candida albicans

Chen

Lan

2020

Microorganisms

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Hepcidin 25 (hep 25) is a cysteine-rich 25-amino acid antimicrobial peptide containing the amino-terminal Cu(II)/Ni(II)-binding (ATCUN) motif. Upon metal binding, the ATCUN motif is known to be involved in the generation of reactive oxygen species (ROS), especially hydrogen peroxide and hydroxyl radicals, which act against different bacterial species. However, the antifungal activity and its correlation to the Cu(II)-ATCUN complex of Hep 25 are still poorly understood. Here, we found that ROS accumulation plays an important role in the fungicidal activity of hep 25 against Candida albicans. In addition, Annexin V-FITC staining and TUNEL assay results provide clues about the apoptosis induced by hep 25. Moreover, hep 25 also increases the generation of ROS, possibly because of copper binding to the ATCUN motif, which is relevant to its activity against C. albicans. Finally, the C. albicans killing action of hep 25 is an energy- and temperature-dependent process that does not involve targeting the membrane. Taken together, our results provide new insights into the mechanisms of hep 25 against C. albicans cells and the potential use of hep 25 and its derivatives as novel antifungal agents.

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Section: Discussionmentioning

confidence: 99%

Human Antimicrobial Peptide Hepcidin 25-Induced Apoptosis in Candida albicans

Chen

Lan

2020

Microorganisms

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“…In the present study, the antifungal peptide CGA-N12 affected the external morphology of Candida cells, reducing the visual thickness of the cell wall at the minimal inhibitory concentration. CGA-N12 is a nonmembrane-active antifungal peptide that can enter C. tropicalis cells without rupturing the plasma membrane [30]. The binding proteins of C. tropicalis cells targeting CGA-N12 were screened by affinity chromatography.…”

Section: Discussionmentioning

confidence: 99%

“…The bacterial pellets were fixed in 5% glutaraldehyde in 20 mmol/l PBS ( pH 7.0) overnight at 4°C. After being washed with PBS, the yeast pellets were fixed with 1% OsO4 in PBS for 2 h. They were then dehydrated by being washed in increasing concentrations (30,50,70, and 95%) of acetone (twice per concentration) for 10 min each and further dehydrated in absolute acetone with three washes at 10 min each. The samples were embedded in Epon 812.…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

“…CGA-N12 induces an overgeneration of intracellular reactive oxygen species and a dissipation of mitochondrial membrane potential. It is capable of inducing apoptosis in C. tropicalis cells through mitochondrial dysfunction and metacaspase activation [30]; however, the effect of CGA-N12 on the C. tropicalis cell wall remains unknown. In the present study, the target of CGA-N12 in Candida was screened by affinity chromatography.…”

Section: Introductionmentioning

confidence: 99%

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The antifungal peptide CGA-N12 inhibits cell wall synthesis of Candida tropicalis by interacting with KRE9

Liu

Dong

et al. 2020

Biochemical Journal

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CGA-N12, an antifungal peptide derived from chromogranin A, has specific antagonistic activity against Candida spp., especially against Candida tropicalis, by inducing cell apoptosis. However, the effect of CGA-N12 on the Candida cell wall is unknown. The Candida protein KRE9, which possesses β-1,6-glucanase activity, was screened by affinity chromatography after binding to CGA-N12. In this study, the effect of CGA-N12 on KRE9 and the interaction between CGA-N12 and KRE9 was studied to clarify the effect of CGA-N12 on C. tropicalis cell wall synthesis. The effect of CGA-N12 on recombinant KRE9 β-1,6-glucanase activity was investigated by analyzing the consumption of glucose. The results showed that CGA-N12 inhibited the activity of KRE9. After C. tropicalis was treated with CGA-N12, the structure of the C. tropicalis cell wall was damaged. The interaction between CGA-N12 and KRE9 was analyzed by isothermal titration calorimetry (ITC). The results showed that their interaction process was involved an endothermic reaction, and the interaction force was mainly hydrophobic with a few electrostatic forces. The results of the fluorescence resonance energy transfer (FRET) assay showed that the distance between CGA-N12 and KRE9 was 7 ∼ 10 nm during their interaction. Therefore, we concluded that the target of CGA-N12 in the C. tropicalis cell membrane is KRE9, and that CGA-N12 weakly binds to KRE9 within a 7 ∼ 10 nm distance and inhibits KRE9 activity.

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“…In our previous work, we found that amino acid sequence from 65th to 76th residue of the N-terminus of CGA (CGA-N12), a more potent and stable derivative of CGA that corresponds to the N-terminal Ala55-Gln76 sequence, exhibits antagonistic activity against Candida species [10]. Our previous studies clarified that CGA-N12 induces mitochondrial depolarization, and cytochrome c (Cyt c) leakage, ultimately causing mitochondria-dependent apoptosis of C. tropicalis [11]. However, the mechanism by which CGA-N12 decreases mitochondrial potential is unclear.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial peptide CGA-N12 decreases the Candida tropicalis mitochondrial membrane potential via mitochondrial permeability transition pore

Zhao

Huang

et al. 2020

Bioscience Reports

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Amino acid sequence from 65th to 76th residue of the N-terminus of Chromogranin A (CGA-N12) is an antimicrobial peptide (AMP). Our previous studies showed that CGA-N12 reduces Candida tropicalis mitochondrial membrane potential. Here, we explored the mechanism that CGA-N12 collapsed the mitochondrial membrane potential by investigations of its action on the mitochondrial permeability transition pore (mPTP) complex of C. tropicalis. The results showed that CGA-N12 induced cytochrome c (Cyt c) leakage, mitochondria swelling and led to polyethylene glycol (PEG) of molecular weight 1000 Da penetrate mitochondria. mPTP opening inhibitors bongkrekic acid (BA) could contract the mitochondrial swelling induced by CGA-N12, but cyclosporin A (CsA) could not. Therefore, we speculated that CGA-N12 could induce C. tropicolis mPTP opening by preventing the matrix-facing (m) conformation of adenine nucleotide transporter (ANT), thereby increasing the permeability of the mitochondrial membrane and resulted in the mitochondrial potential dissipation.

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CGA-N12, a peptide derived from chromogranin A, promotes apoptosis of Candida tropicalis by attenuating mitochondrial functions

Cited by 18 publications

References 53 publications

Human Antimicrobial Peptide Hepcidin 25-Induced Apoptosis in Candida albicans

Human Antimicrobial Peptide Hepcidin 25-Induced Apoptosis in Candida albicans

The antifungal peptide CGA-N12 inhibits cell wall synthesis of Candida tropicalis by interacting with KRE9

Antimicrobial peptide CGA-N12 decreases the Candida tropicalis mitochondrial membrane potential via mitochondrial permeability transition pore

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