Effect of tryptophan position and lysine/arginine substitution in antimicrobial peptides on antifungal action
Every year, the overprescription, misuse, and improper disposal of antibiotics have led to the rampant development of drug-resistant pathogens and, in turn, a significant increase in the number of patients who die of drug-resistant fungal infections. Recently, researchers have begun investigating th...
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Published in | Biochemical and biophysical research communications Vol. 704; p. 149700 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
16.04.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Every year, the overprescription, misuse, and improper disposal of antibiotics have led to the rampant development of drug-resistant pathogens and, in turn, a significant increase in the number of patients who die of drug-resistant fungal infections. Recently, researchers have begun investigating the use of antimicrobial peptides (AMPs) as next-generation antifungal agents to inhibit the growth of drug-resistant fungi. The antifungal activity of alpha-helical peptides designed using the cationic amino acids containing lysine and arginine and the hydrophobic amino acids containing isoleucine and tryptophan were evaluated using 10 yeast and mold fungi. Among these peptides, WIK-14, which is composed of a 14-mer with tryptophan sequences at the amino terminus, showed the best antifungal activity via transient pore formation and ROS generation. In addition, the in vivo antifungal effects of WIK-14 were investigated in a mouse model infected with drug-resistant Candida albicans. The results demonstrate the potential of AMPs as antifungal agents.
•Antimicrobial peptides exhibit multifaceted activity against drug-resistant fungi.•Peptides can be improved for in vivo application by strategic substitutions.•Modified peptides exhibited antifungal activity through multiple mechanisms.•Peptides reduced cytokines and histopathological lesions in mouse C. albicans model. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0006-291X 1090-2104 1090-2104 |
DOI: | 10.1016/j.bbrc.2024.149700 |