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

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. Here, scanning electron microscopy and fluorescence microscopy were employed to evaluate the mechanisms of anticandidal action of two synthetic peptides. The peptides induced several damages to Candida cells leading to death. The clinical application of peptides as adjuvants was assessed by synergism activity with nystatin, a commercial drug. Peptides improved in 675 times nystatin action, showing their potential as an adjuvant to improve nystatin action and reduce its collateral damage.