Cathelicidins in the Tasmanian devil (Sarcophilus harrisii)
Antimicrobial resistance is increasing, posing a threat to human and animal health. A lack of new antibiotics means alternatives such as antimicrobial peptides are urgently required. 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 altricial young which are immunologically naïve. During development the young are protected from infection by mechanisms such as cathelicidins within the pouch. This unique reproductive physiology has encouraged lineage specific expansion of the cathelicidin gene family within marsupials, resulting in numerous diverse peptides.
The Tasmanian devil (Sarcophilus harrisii) is the largest remaining carnivorous marsupial and is currently under threat from a contagious cancer, devil facial tumour disease (DFTD). Human and bovine cathelicidins exhibit anti-tumour activity against a number of cancers. Furthermore, studies in the tammar wallaby have revealed the potency of marsupial cathelicidins against multi-drug resistant bacteria. As such, release of the Tasmanian devil genome in 2012 provides new avenues in the search for cathelicidins with the therapeutic potential to treat DFTD and resistant pathogens.
We identified 7 cathelicidins in the Tasmanian devil genome which were highly variable and distantly related to eutherian cathelicidins. Six Tasmanian devil cathelicidins have been synthesised and will be tested against a range of bacteria and fungi. Preliminary antifungal testing of two cathelicidins revealed that one peptide was more effective at killing Candida krusei, Candida parapsilosis, Cryptococcus gattii and Cryptococcus neoformans than the antifungal drug fluconazole. Cytotoxic and haemolytic activity of all six cathelicidins has also been determined. Four cathelicidins did not kill human lung epithelial cells or red blood cells, and only two showed moderate cytotoxic and haemolytic activity. This study highlights the potential for marsupials such as the Tasmanian devil to provide new drugs to treat human and animal disease.