Antimicrobial peptides are a primitive component of the innate immune system. Cathelicidins are a predominant family within mammals, contributing to host immunity through antimicrobial and immunomodulatory functions. They have been studied extensively in eutherian mammals but marsupials are relatively unexplored. Marsupials give birth to immunologically naïve young which are protected from infection by cathelicidins in the pouch. This unique reproductive physiology has encouraged lineage specific expansion of the cathelicidin gene family, resulting in numerous diverse peptides.

The Tasmanian devil (Sarcophilus harrisii) is under threat from a contagious cancer, devil facial tumour disease (DFTD). Human and bovine cathelicidins exhibit anti-tumour activity against a number of cancers. Studies in the tammar wallaby have revealed the potency of marsupial cathelicidins against drug resistant bacteria. As such, the Tasmanian devil genome provides new avenues in the search for cathelicidins with therapeutic potential to treat DFTD and resistant pathogens.

We identified six cathelicidins in the Tasmanian devil genome. Transcriptome BLAST searches show that cathelicidins are expressed in the spleen, lymph node, testis, milk and devil facial tumour. A multiple sequence alignment reveals that Tasmanian devil cathelicidins are highly variable within this species, and amongst other marsupial (tammar wallaby 19-70% similarity) and eutherian (human 34-49% similarity) cathelicidins. The sequence alignment was used to construct a neighbour joining phylogenetic tree. As expected, Tasmanian devil cathelicidins cluster with other marsupials and are distantly related to eutherians. Two Tasmanian devil peptides were orthologous to a tammar wallaby and grey short-tailed opossum cathelicidin, demonstrating the existence of ancestral cathelicidins.

Two Tasmanian devil putative mature peptides were synthesised and tested against a range of fungal pathogens. One peptide was capable of killing Candida krusei, Candida parapsilosis and was 3 and 6 times more effective against Cryptococcus neoformans and Cryptococcus gattii respectively, than the antifungal drug fluconazole. In future studies, all six cathelicidins will be tested against a range of resistant bacterial pathogens and DFTD cells. This study highlights the potential of marsupials such as the Tasmanian devil to provide new drugs to treat human and animal disease.