*3.2. Mechanisms Underlying the Antifungal and Antiyeast Activities of CST*

The composition of fungal cell membranes is similar to that of bacteria, comprising zwitterionic and anionic phospholipids. In contrast, the fungal cell wall is composed of chitin, glucan, ergosterol, and mannoprotein, which reside on the surface of the cytoplasmic membrane. Because of the negative charge on the cytoplasmic membrane, CST could exert its anti-fungal activities in a similar way to its antibacterial activity. Metz-Boutigue's group used confocal laser microscopy to analyze the interaction of the synthetic rhodamine-labeled cateslytin (bCgA344–358R) with fungal (*A. fumigatus*) and yeast (*C. albicans*) membranes [21]. Rhodaminated cateslytin (1 μM) was detected in the inner compartment after 2 min of incubation, implicating rapid and efficient penetration through the cell wall [21]. Using time-lapse video microscopy of fungal growth, they have shown that rhodaminated cateslytin blocked the growth and development of nascent fungus [21]. Penetration of rhodaminated cateslytin takes place at both ends of the small fungi (three cells and expressing a slow growth rate) as compared to larger fungi with a higher growth rate where penetration takes place at one end [21]. Sequence homology of the well-known cell-permeable peptide penetratin with CST representing seven mammalian orders (Primates, Rodentia, Artiodactyla, Perissodactyla, Carnivora, Cetacea, and Monotremata) revealed 63.64% to 75% similarity, which should qualify CST as a cell-permeable peptide (Figure 5).


**Figure 5.** Homology between cell permeable peptide penetratin and CST in seven mammalian orders.
