## 4 Antifungal Peptides  
The concern generated by bacterial infections goes hand in hand with that of fungal infections especially considering both the frequency and the rapidity their resistance develops and spreads and the poor arsenal of available antifungal drugs. Fungal infections become extremely threatening especially for certain categories represented by patients with a compromised immune system due to pathological conditions, such as HIV/AIDS or autoimmune diseases and to therapeutic outcomes like chemotherapy and organ transplantation [101]. Among the fungal species _Candida albicans_, _Apergillus fumigatus_, _Cryptococcus neoformans_ and _Pneumocystis jirovecii_ are the main ones responsible for the majority of severe mycoses [102] with 90% of reported deaths [103]. Among the emerging and reemergingspecies, such as _Histoplasma capsulatum_ and _Fusarium_ spp., of note is _Candida auris_ which is considered by the Centre for Disease Control and Prevention (CDC) as an urgent global threat for its multi-drug resistance [18; 104]. The latest reports highlight also the need for efficient treatments that nowadays are based only on three major classes of antifungal drugs: azoles, echinocandins and polyenes. Of these classes, echinocandins originated from non-ribosomal AMPs synthetically optimized [101]. Fungi are eukaryotic organisms; hence, they share with mammalian cells high similarities making it difficult to identify suitable targets while minimizing the risk of adverse effects. Although toxicity is an important issue, synthetic modifications of AMPs structures have extremely improved safety leaving just a few exceptions mainly represented by erythrocyte hemolysis and nucleic acid damages [105; 106; 107]. As previously seen for antibacterial AMPs, peptides with antifungal activity may present improved affinity towards phospholipids of the fungal membrane (phosphatidylserine and phosphatidylethanolamine) suggesting a distinctive relation between structure and activity (Figure 1a (C)) [108]. The three models used to describe the pore generated in bacterial membranes (_carpetlike_, _barrel-stave_ and _toroidal_) are applicable also for AMPs acting on fungal membranes. Interestingly amphotericin B, the major representative of the polyene class of antifungal drugs, behaves as _barrel-stave_-pore forming peptide [101]. Evidence has demonstrated the existence of AMPs acting on the fungal membrane and on its components without having always clear information about their mechanism of action. Often these peptides affect the permeability of the membrane leading to ROS accumulation, oxidative stress damages, ATP release and the activation of stress-response pathways as HOG and MAPK cascade [109; 110; 111]. On the other hand, just a few AMPs have been revealed to interact with membrane components like glucosylceramides and \(\beta\)-1,3-glucans or with enzymes involved in the production of membrane components as the inositol phosphoryl ceramide synthase which is essential for the sphingolipid biosynthesis [112; 113; 114]. Membrane-active peptides have good potential and a broad-spectrum that sometimes includes both bacteria and fungi, nevertheless, as some AMPs with exclusive antifungal properties exist, it is also the case of antimicrobial peptides active against the cell wall (Figure 1b). The cell wall is an external structure proper of fungi unique in its composition since rich in glucans, chitin and mannan. The development of cell wall-active-AMPs grants high levels of safety with no or minor toxicity for mammalian cells. Most of the AMPs interfere with the synthesis of the wall components, such as \(\beta\)-1,3-glucan synthase fundamental enzyme for the production of \(\beta\)-1,3-glucans hence for the maintenance of the structural integrity (echinocandins exert this mechanism of action) and chitin synthase essential for chitin production [106]. Mannan and its glyco--and proteo-conjugates are deeply involved in fungal virulence, biofilm formation and adhesion to both biotic and abiotic surfaces included.