Crocodile defensin (CpoBD13) antifungal activity via pH-dependent phospholipid targeting and membrane disruption

Abstract

Crocodilians are an order of ancient reptiles that thrive in pathogen-rich environments. The ability to inhabit these harsh environments is indicative of a resilient innate immune system. Defensins, a family of cysteine-rich cationic host defence peptides, are a major component of the innate immune systems of all plant and animal species, however crocodilian defensins are poorly characterised. We now show that the saltwater crocodile defensin CpoBD13 harbors potent antifungal activity that is mediated by a pH-dependent membrane-targeting action. CpoBD13 binds the phospholipid phosphatidic acid (PA) to form a large helical oligomeric complex, with specific histidine residues mediating PA binding. The utilisation of histidine residues for PA engagement allows CpoBD13 to exhibit differential activity at a range of environmental pH values, where CpoBD13 is optimally active in an acidic environment.

Embracing the era of antimicrobial peptides with marine organisms

“…Defensin is one of the earliest identified AMPs and it has been found in various kinds of animals including mammals, insects, and marine fish. 32–34 Defensin can be classified into α-, β-, and θ-defensins. Based on sequence prediction, only β-defensins are found in marine fish, compared to the existence of both α- and β-defensins in mammals.…”