Genetic mechanisms and biological processes underlying host response to ophidiomycosis (Snake Fungal Disease) inferred from tissue-specific transcriptome analyses

There is growing concern about infectious diseases in wildlife species caused by pathogenic fungi. Detailed knowledge exists about host pathology and the molecular mechanisms underlying host physiological response to some fungal diseases affecting amphibians and bats but is lacking for others with potentially significant impacts on large groups of animals. One such disease is ophidiomycosis (Snake Fungal Disease; SFD) which is caused by the fungus Ophidiomyces ophidiicola and impacts diverse species of snakes. Despite this potential, the biological mechanisms and molecular changes occurring during infection are unknown for any snake species. To gain this information, we performed a controlled experimental infection of captive Prairie rattlesnakes (Crotalus viridis) with O. ophidiicola at different temperatures. We then generated liver, kidney, and skin transcriptomes from control and infected snakes to assess tissue specific genetic responses to infection. Given previous SFD histopathological studies and the fact that snakes are ectotherms, we expected highest fungal activity on skin and a significant impact of temperature on host response. In contrast, we found that most of the differential gene expression was restricted to internal tissues and fungal-infected snakes showed transcriptome profiles indicative of long-term inflammation of specific tissues. Infected snakes at the lower temperature had the most pronounced overall host functional response whereas, infected snakes at the higher temperature had overall expression profiles similar to control snakes possibly indicating recovery from the disease. Overall, our results suggest SFD is a systemic disease with a chronic host response, unlike acute response shown by amphibians to Batrachochytrium dendrobatidis infections. Our analysis also generated a list of candidate protein coding genes that potentially mediate SFD response in snakes, providing tools for future comparative and evolutionary studies into variable species susceptibility to ophidiomycosis. Author summary Ophidiomycosis (Snake Fungal Disease; SFD) is an infectious fungal disease in snakes that has been documented in more than 40 species over the past 20 years. Though many snake species seem vulnerable to SFD, little is known about how snake physiology changes in response to infection with the causative fungus, Ophidiomyces ophidiicola. Here we report results from the first experimental transcriptomic study of SFD in a snake host. Our goals were to identify genes with a putative role in host response, use this information to understand what biological changes occur in different tissues in snakes when infected with O. ophidiicola, and determine if temperature has an impact in these ectothermic animals. We conclude that SFD is a systemic disease with a chronic inflammation leading to deterioration of internal organs and that these physiological impacts are more pronounced at low rather than high temperatures. These results contrast with fungal infections in amphibians where hosts show an acute response mostly restricted to skin. Our list of candidate genes carry utility in potentially diagnosing genetic susceptibility to SFD in snake species of conservation concern.