More than Skin Deep: Functional Genomic Basis for Resistance to Amphibian Chytridiomycosis

Abstract

The amphibian-killing chytrid fungus Batrachochytrium dendrobatidis (Bd) is one of the most generalist pathogens known, capable of infecting hundreds of species globally and causing widespread population declines and extinctions. However, some host species are seemingly unaffected by Bd, tolerating or clearing infections without clinical signs of disease. Variation in host immune responses is commonly evoked for these resistant or tolerant species, yet to date, we have no direct comparison of amphibian species responses to infection at the level of gene expression. In this study, we challenged four Central American frog species that vary in Bd susceptibility, with a sympatric virulent strain of the pathogen. We compared skin and spleen orthologous gene expression using differential expression tests and coexpression gene network analyses. We found that resistant species have reduced skin inflammatory responses and increased expression of genes involved in skin integrity. In contrast, only highly susceptible species exhibited suppression of splenic T-cell genes. We conclude that resistance to chytridiomycosis may be related to a species’ ability to escape the immunosuppressive activity of the fungus. Moreover, our results indicate that within-species differences in splenic proteolytic enzyme gene expression may contribute to intraspecific variation in survival. This first comparison of amphibian functional immunogenomic architecture in response to Bd provides insights into key genetic mechanisms underlying variation in disease outcomes among amphibian species.

Environmental fluctuations and host skin bacteria shift survival advantage between frogs and their fungal pathogen

“…Because skin sloughing is a costly potential mechanism of defense, and we saw no reduction in pathogen load, we hypothesize that this mechanism contributes to tolerance in a different way. If sloughing in coqui frogs serves to maintain infections at bay for a fixed amount of time (cool-dry season), then this strategy could protect the host during a time that immune responses are slow, ineffective, or potentially damaging (Ellison et al, 2015). Sloughing should be further explored using microscopy or molecular techniques to determine the viability of bacteria and Bd.…”

First in Vivo Batrachochytrium dendrobatidis Transcriptomes Reveal Mechanisms of Host Exploitation, Host-Specific Gene Expression, and Expressed Genotype Shifts

“…Gene expression raw read counts were obtained for both host and pathogen using RSEM v1.2.2 (Li and Dewey 2011). As H. lemur has no available transcriptome, reads were first mapped to the Bd transcriptome, and then unmapped reads were pooled from all samples and de novo assembled into H. lemur transcripts using previously published pipelines utilizing the Trinity assembly package (Haas et al 2013; Ellison et al 2014, 2015). …”

“…Therefore, pathogens require finely tuned expression of genes during the dynamic infection process, allowing them to counter or evade host defense responses, and acquire nutrients to invest in growth and reproduction. For generalist pathogens, each host species represents a distinct selective environment, providing host-specific defense mechanisms to counter, and unique conditions for resource acquisition (Ellison et al 2015), potentially contributing to observed differences in pathogen fitness on different hosts. Thus, modulation of gene expression should be advantageous to generalist pathogens, responding optimally to a given host and mitigating costs of generalism (Leggett et al 2013).…”

Overview of chytrid emergence and impacts on amphibians

“…Still, some biotic (e.g. variation in pathogen virulence [12,16]; host ecology [10]; immunogenetic variation [17][18][19]; antimicrobial peptides [20]; skin bacteria [21,22]) and abiotic (e.g. temperature and moisture [23]; habitat [10]) factors have consistently been associated with higher probabilities of population persistence or decline across many locations.…”