Anticandidal activity of synthetic peptides: Mechanism of action revealed by scanning electron and fluorescence microscopies and synergism effect with nystatin

被引:24
|
作者
Lima, Patricia G. [1 ]
Souza, Pedro F. N. [1 ]
Freitas, Cleverson D. T. [1 ]
Oliveira, Jose T. A. [1 ]
Dias, Lucas P. [1 ]
Neto, Joao X. S. [1 ]
Vasconcelos, Ilka M. [1 ]
Lopes, Jose L. S. [2 ]
Sousa, Daniele O. B. [1 ]
机构
[1] Univ Fed Ceara, Dept Biochem & Mol Biol, Fortaleza, Ceara, Brazil
[2] Univ Sao Paulo, Dept Appl Phys, Sao Paulo, Brazil
关键词
anticandidal action; Candida albicans; cell wall rupture; Mo-CBP3; peptides; pore formation; synthetic antimicrobial peptide; MEMBRANE DISRUPTION; ANTIFUNGAL ACTIVITY; SELECTIVITY; CANDIDEMIA; RESISTANCE; DELIVERY; INSIGHT; PROTEIN; SEED; ROS;
D O I
10.1002/psc.3249
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Candida albicans has emerged as a major public health problem in recent decades. The most important contributing factor is the rapid increase in resistance to conventional drugs worldwide. Synthetic antimicrobial peptides (SAMPs) have attracted substantial attention as alternatives and/or adjuvants in therapeutic treatments due to their strong activity at low concentrations without apparent toxicity. Here, two SAMPs, named Mo-CBP3-PepI (CPAIQRCC) and Mo-CBP3-PepII (NIQPPCRCC), are described, bioinspired by Mo-CBP3, which is an antifungal chitin-binding protein from Moringa oleifera seeds. Furthermore, the mechanism of anticandidal activity was evaluated as well as their synergistic effects with nystatin. Both peptides induced the production of reactive oxygen species (ROS), cell wall degradation, and large pores in the C. albicans cell membrane. In addition, the peptides exhibited high potential as adjuvants because of their synergistic effects, by increasing almost 50-fold the anticandidal activity of the conventional antifungal drug nystatin. These peptides have excellent potential as new drugs and/or adjuvants to conventional drugs for treatment of clinical infections caused by C. albicans.
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页数:13
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