*3.1. Inhibition of Growth of Fungus and Yeast by CST*

Fungal infections are common on the surface of skin, nails, or mucous membranes (superficial or mucocutaneous), underneath the skin (subcutaneous), or in the lungs, brain, or heart (deep infection). Deep fungal infections include Histoplasmosis [58], Coccidioidomycosis (Valley fever) [59], Blastomycosis [60], Aspergillosis [61], Candidal urinary tract infection [62], invasive candidiasis [63,64], *Pneumocystis* pneumonia [65], Mucormycosis [66,67], and Cryptococcosis [68,69]. It is becoming increasingly evident that resistance to antifungal therapy is on the rise [70,71], which calls for the development of alternative therapy for these infections. Host-defense peptides are emerging as new promising candidates to counteract antifungal resistance [72]. To this end, Metz-Boutigue's group tested the effects of CST on the growth of fungus and yeasts. They found MIC values of CST or its human variants ranging from 0.2 μM to 75 μM against a host of fungal species (*Neurospora crassa*, *Aspergillus fumigatus*, *A. niger*, *Nectria haematococca*, *Fusarium culmorum*, *F. oxysporum*, *Trichophyton mentagrophytes*, and *T. rubrum*) [21,24] (Figure 3). The MIC100 values of CST or its human variants against the above fungal species ranged from 0.8 μM to 100 μM [21,24] (Figure 3). CST and its human variants also displayed similar inhibitory effects on the growth of yeasts, with MIC ranging from 1.2 μM to >240 μM (Figure 3) [21,24]. The MIC100 of CST and its variants against the above yeasts ranged from 6 μM to 75 μM [21,24] (Figure 4). Similar to the effects of retro-inverso (RI)-CST (Amino-lqpGpGrfGyararfslkmss-carboxyl, with the CST sequence reversed from carboxyl → amino, and chirality was inversed from L → D) on catecholamine secretion [73], D-CST exhibited comparable inhibitory effects on the growth of yeast compared to L-CST with MIC ranged from 2 μM to 9.6 μM [23]. D-CST was also uncovered to be resistant to proteolytic digestion [23,44,74]. Akin to L-CST, D-CST can also be used to develop therapies for drug-resistant microbial infection [75].


**Figure 3.** Effects of WT-CST and natural human variants of CST (Gly364Ser and Pro370Leu) on the growth of fungal species showing MIC and MIC100 of CST.


**Figure 4.** Effects of WT-CST and natural human variants of CST (Gly364Ser and Pro370Leu) on the growth of yeast species showing MIC and MIC100 of CST.
