New potential antimicrobial peptides with amazing symmetrical structure in fungi and insects

Abstract We have discovered a new family of genes encoding potential antimicrobial peptides with unique compact and elegant structure in the genomes of several Fungi and some arthropod species. Their expression products are constituted of about 85 amino acids, including a signal peptide, and are folded into two α-helical segments connected by a short unstructured coil. Three conserved disulphide bridges between cysteines located in symmetrically mirrored positions connect the two helical domains. The two ends of the chain are thus brought together and the elongated and compact shape suggests that of a nail, potentially able to penetrate the cell membrane. A high abundance of hydrophobic residues supports such hypothesis. These peptides, that we name Hairpin Loop Peptides (HLPs), have been found in the genomes of many Fungi species but only in selected clades. Orthologues have also been discovered in the genomes of some insects, notably Hemiptera, a few other arthropods and other organisms, but are absent in plants. They appear to have originated in Fungi and then migrated to insects through horizontal gene transfer. The antimicrobial activity of HLPs is predicted by several software programmes, although this still needs to be confirmed by experimental evidence. The occurrence of HLPs in several edible mushrooms supports potential uses of these peptides in food preservation and possibly also in medical applications. Their simple and nearly rigid structure can be easily modified to improve specificity, stability and solubility, thus making these molecular weapons suitable for a variety of different applications. Significance statement The increasing emergence of bacteria resistant to current antibiotics has stimulated a rapid search for alternative treatments. In recent years, antimicrobial peptides have attracted considerable interest for their potential applications in medicine and as food preservatives. We have identified a new class of peptides primarily expressed in fungi, including edible mushrooms, and also detected in some insects and other arthropods, likely as a result of horizontal gene-transfer events. These peptides are particularly noteworthy because of their compact, elongated, and highly symmetrical structures, which give them a nail-like shape capable of penetrating cellular membranes. Such structural features suggest potential antimicrobial activity, a prediction supported by computational analyses. Their widespread presence in edible mushrooms further indicates the potential safety of these peptides for human use. Competing Interest Statement The authors have declared no competing interest.