Cathelicidins in the Tasmanian devil (Sarcophilus harrisii) (#110)
The
Tasmanian devil (Sarcophilus harrisii)
is the largest remaining carnivorous marsupial. The future of the Tasmanian
devil is under threat from a contagious cancer, Devil Facial Tumour Disease
(DFTD), which has already decimated over 85% of the population. Interestingly, young
devils do not catch DFTD, and we hypothesize that antimicrobial peptides within
the mother’s milk may protect the young against infection. Cathelicidins are a
family of antimicrobial peptides within mammals which contribute to innate
immunity through antimicrobial and immunomodulatory functions. They have been studied
extensively in eutherian mammals but marsupials are relatively unexplored.
Marsupials have a short gestation period and give birth to altricial young which are
immunologically naive. During development the young are protected from microbial
infection by cathelicidins expressed in the mother’s milk, pouch epithelium and
skin of the young themselves. This unique reproductive physiology has encouraged lineage specific expansion of the cathelicidin gene family within
marsupials, resulting in numerous diverse peptides. We identified six
cathelicidins in the Tasmanian devil genome and have synthesized the mature
peptides. These will be tested against a range of pathogens, including DFTD
cells. Thus far only bacteria and fungi have been tested, with promising results.
One cathelicidin was more effective at killing Cryptococcus gattii and Cryptococcus
neoformans than the antifungal drug fluconazole. Furthermore, two
cathelicidins were capable of killing methicillin-resistant Staphylococcus aureus, vancomycin
resistant Enterococci and numerous
human clinical isolates. Cytotoxic and haemolytic activity of all cathelicidins
against human cells has also been determined and only two are moderately toxic.
This study highlights the potential for marsupials such as the Tasmanian devil
to provide new drugs to treat human and animal disease.