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Anti-fungal Effects and Mechanisms of Action of Wasp Venom-Derived Peptide Mastoparan-VT1 Against Candida albicans

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Abstract

Candida albicans, an opportunistic yeast pathogen, is equipped with a plethora of virulence attributes such as yeast-to-hyphae transition, secreted enzymes, tissue adhesion, and biofilm production. The dearth of effective anti-mycotics together with the emergence of drug-resistant C. albicans isolates underscore the need to explore novel anti-fungal agents. Anti-microbial peptides (AMPs) have recently awakened considerable interest as potential therapeutic agents. The intent of this study is to assess anti-fungal effects of Mastoparan VT-1 (MP-VT1), an AMP from the venom of social wasp Vespa tropica, against planktonic and biofilm-embedded cells of C. albicans. MP-VT1 had a tendency to adopt alpha-helical conformation based on peptide secondary structure prediction and circular dichroism spectroscopy (in 50% trifluoroethanol). The peptide showed MIC values ranging from 2 to 32 µg/mL against 10 clinical strains of C. albicans. Notably, a 6-h of exposure to 1 × MFC of MP-VT1 sufficed for total yeast clearance. At fungicidal concentrations, MP-VT1 exhibited slight cytotoxicity towards human dermal fibroblasts. Flow cytometric analysis and fluorescence microscopy revealed that MP-VT1 induced membrane disruption, leading to death of C. albicans mainly by necrosis. Interestingly, a significant inhibition of hyphal transition was noticed at 3 and 6 h post-contact with 32 µg/mL of MP-VT1. At sub-lethal concentrations, the peptide lessened not only candidal cell surface hydrophobicity but also the number of yeasts adhering to the polystyrene surfaces. Furthermore, C. albicans cells within biofilms were more vulnerable to MP-VT1 than to fluconazole. Overall, MP-VT1 has the potential to be used as a candidate for anti-fungal drug development.

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Abbreviations

AMPs:

Anti-microbial peptides

AO/EtBr:

Acridine orange/ethidium bromide

CD:

Circular dichroism

CFUs:

Colony forming units

CSH:

Cell surface hydrophobicity

DMEM:

Dulbecco’s Modifed Eagle’s Medium

DMSO:

Dimethyl sulfoxide

FCS:

Fetal calf serum

FITC:

Fluorescein isothiocyanate

HFFs:

Human foreskin fibroblasts

MFC:

Minimum fungicidal concentration

MIC:

Minimum inhibitory concentration

MP-VT1:

Mastoparan VT-1

MOPS:

3-(N-Morpholino) propane sulfonic acid

OD:

Optical density

PBS:

Phosphate-buffered saline

PI:

Propidium iodide

RP-HPLC:

Reversed phase–high-performance liquid chromatography

RPMI 1640:

Roswell Park Memorial Institute 1640

SD:

Standard deviation

SDA:

Sabouraud dextrose agar

SDB:

Sabouraud dextrose broth

TFE:

2,2,2-Trifluoroethanol

YNBG:

Yeast nitrogen base medium containing 2% glucose

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Authors and Affiliations

Authors

Contributions

MM and HM jointly contributed to all phases of this study (conception, experimental design, data analysis, practical work, and authorship of the manuscript). ZP and ZB partially participated in practical work. HM critically reviewed and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hamed Memariani.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical Approval

The manuscript does not contain experiments involving animal or human studies.

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Fig. S1

RP-HPLC chromatogram (a) and mass spectrum (b) of synthetic mastoparan VT-1 (INLKAIAALAKKLL—NH2). In panel a, insert represents additional information on retention time (RT), peak area, peak height, and % area. As shown in panel a, the large peak assigned with the black arrow represents the purified peptide. (TIF 2647 KB)

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Memariani, M., Memariani, H., Poursafavi, Z. et al. Anti-fungal Effects and Mechanisms of Action of Wasp Venom-Derived Peptide Mastoparan-VT1 Against Candida albicans. Int J Pept Res Ther 28, 96 (2022). https://doi.org/10.1007/s10989-022-10401-5

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  • DOI: https://doi.org/10.1007/s10989-022-10401-5

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