AMPed Up Immunity: 418 Whole Genomes Reveal Intraspecific Diversity of Koala Antimicrobial Peptides

Type: Journal article

Reference: Petrohilos C, Peel E, Silver LW, Belov K, Hogg CJ. AMPed up immunity: 418 whole genomes reveal intraspecific diversity of koala antimicrobial peptides. Immunogenetics. 2025 Jan 8;77(1):11. doi: 10.1007/s00251-024-01368-2.

Abstract

Characterising functional diversity is a vital element to understanding a species’ immune function, yet many immunogenetic studies in non-model organisms tend to focus on only one or two gene families such as the major histocompatibility complex (MHC) or toll-like receptors (TLR). Another interesting component of the eukaryotic innate immune system is the antimicrobial peptides (AMPs). The two major groups of mammalian AMPs are cathelicidins and defensins, with the former having undergone species-specific expansions in marsupials. Here, we utilised data from 418 koala whole genomes to undertake the first comprehensive analysis of AMP diversity across a mammalian wildlife species’ range. Overall, allelic diversity was lower than other immune gene families such as MHC, suggesting that AMPs are more conserved, although balancing selection was observed in PhciDEFB12. Some non-synonymous SNPs in the active peptide are predicted to change AMP function through stop gains, change in structure, and increase in peptide charge. Copy number variants (CNVs) were observed in two defensins and one cathelicidin. Interestingly, the most common CNV was the duplication of PhciCATH5, a cathelicidin with activity against chlamydia, which was more common in the southern part of the species range than the north. AMP copy number is correlated with expression levels, so we hypothesise that there is a selective pressure from chlamydia for duplications in PhciCATH5. Future studies should use phenotypic metadata to assess the functional impacts of this gene duplication.

Tasmanian devil cathelicidins exhibit anticancer activity against Devil Facial Tumour Disease (DFTD) cells

Type: Journal Article

Reference: Petrohilos, C., Patchett, A., Hogg, C.J. et al. Tasmanian devil cathelicidins exhibit anticancer activity against Devil Facial Tumour Disease (DFTD) cells. Science Report 13, 12698 (2023). doi: 10.1038/s41598-023-39901-0

Abstract

The Tasmanian devil (Sarcophilus harrisii) is endangered due to the spread of Devil Facial Tumour Disease (DFTD), a contagious cancer with no current treatment options. Here we test whether seven recently characterized Tasmanian devil cathelicidins are involved in cancer regulation. We measured DFTD cell viability in vitro following incubation with each of the seven peptides and describe the effect of each on gene expression in treated cells. Four cathelicidins (Saha-CATH3, 4, 5 and 6) were toxic to DFTD cells and caused general signs of cellular stress. The most toxic peptide (Saha-CATH5) also suppressed the ERBB and YAP1/TAZ signaling pathways, both of which have been identified as important drivers of cancer proliferation. Three cathelicidins induced inflammatory pathways in DFTD cells that may potentially recruit immune cells in vivo. This study suggests that devil cathelicidins have some anti-cancer and inflammatory functions and should be explored further to determine whether they have potential as treatment leads.