Nicotianin-I: A Tobacco Floral Nectar Peptide with Anticandidal Activity.

Multidrug-resistant microorganisms are major threats to society, leading to the necessity of alternative molecules to fight them back. Antimicrobial peptides (AMPs), especially those derived from plants, have become relevant for multiple reasons. Therefore, this study evaluated six peptides identified in the floral nectar of ornamental tobacco for their effectiveness against four clinically relevant yeast species (Candida albicans, Candida krusei, Candida parapsilosis, and Candida tropicalis). Pep6 (KHYSCTRHGYCLACYKRWF) was the only one that showed activity against all yeast species, with IC50 values ranging from 24 ± 1.9 μM to 80 ± 4.6 μM. Pep6 (named nicotianin-I) was able to alter permeability or generate pores in the cell membranes of all microorganisms, in addition to inducing an overproduction of reactive oxygen species (ROS). Nicotianin-I adopted a structure similar to that of the polyproline II (PPII) helix in buffer and sodium dodecyl sulfate (SDS) and an α-helical pattern when subjected to a membrane mimetic environment (50% TFE). It demonstrated negligible hemolytic activity and no cytotoxic effects on murine fibroblast cells. Only at the highest concentration assessed (100 μg/mL or 42 μM), nicotianin-I caused a 40% mortality rate in zebrafish embryos and delayed their hatching. This study demonstrates the potential of a novel peptide with anticandidal activity and opens the door to the rational design of new analogous peptides with improved properties.