Project description:Amphibian populations around the world are threatened by an emerging infectious pathogen, the chytrid fungus Batrachochytrium dendrobatidis (Bd). How can a fungal skin infection kill such a broad range of amphibian hosts? And why are certain species particularly susceptible to the impacts of Bd? Here we use a genomics approach to understand the genetic response of multiple susceptible frog species to Bd infection. We characterize the transcriptomes of two closely-related endangered frog species (Rana muscosa and Rana sierrae) and analyze whole genome expression profiles from frogs in controlled Bd-infection experiments. We integrate the Rana results with a comparable dataset from a more distantly-related susceptible species (Silurana tropicalis). We demonstrate that Bd-infected frogs show massive disruption of skin function and show no evidence of a robust immune response. The genetic response to infection is shared across the focal susceptible species, suggesting a common effect of Bd on susceptible frogs. A total of five (12-plex) chips were analyzed from 60 samples comprising 2 conditions (control and infected), 3 tissues (skin, liver and spleen) and 2 timepoints (early and late). Three biological replicates were used for each condition and tissue at each time point. Twentyfour arrays were analyzed for skin samples, 24 for liver, and 12 for spleen. The same dye, Cy5, was used for all samples.
Project description:Amphibian populations around the world are threatened by an emerging infectious pathogen, the chytrid fungus Batrachochytrium dendrobatidis (Bd). How can a fungal skin infection kill such a broad range of amphibian hosts? And why are certain species particularly susceptible to the impacts of Bd? Here we use a genomics approach to understand the genetic response of multiple susceptible frog species to Bd infection. We characterize the transcriptomes of two closely-related endangered frog species (Rana muscosa and Rana sierrae) and analyze whole genome expression profiles from frogs in controlled Bd-infection experiments. We integrate the Rana results with a comparable dataset from a more distantly-related susceptible species (Silurana tropicalis). We demonstrate that Bd-infected frogs show massive disruption of skin function and show no evidence of a robust immune response. The genetic response to infection is shared across the focal susceptible species, suggesting a common effect of Bd on susceptible frogs.
Project description:Emerging infectious diseases are of great concern for both wildlife and humans. Several highly virulent fungal pathogens have recently been discovered in natural populations, highlighting the need for a better understanding of fungal-vertebrate host-pathogen interactions. Because most fungal pathogens are not fatal in the absence of other predisposing conditions, host-pathogen dynamics for deadly fungal pathogens are of particular interest. The chytrid fungus Batrachochytrium dendrobatidis (hereafter Bd) infects hundreds of species of frogs in the wild. It is found worldwide and is a significant contributor to the current global amphibian decline. However, the mechanism by which Bd causes death in amphibians, and the response of the host to Bd infection, remain largely unknown. Here we use whole-genome microarrays to monitor the transcriptional responses to Bd infection in the model frog species, Silurana (Xenopus) tropicalis, which is susceptible to chytridiomycosis. To elucidate the immune response to Bd and evaluate the physiological effects of chytridiomycosis, we measured gene expression changes in several tissues (liver, skin, spleen) following exposure to Bd. We detected a strong transcriptional response for genes involved in physiological processes that can help explain some clinical symptoms of chytridiomycosis at the organismal level. However, we detected surprisingly little evidence of an immune response to Bd exposure, suggesting that this susceptible species may not be mounting efficient innate and adaptive immune responses against Bd. The weak immune response may be partially explained by the thermal conditions of the experiment, which were optimal for Bd growth. However, many immune genes exhibited decreased expression in Bd-exposed frogs compared to control frogs, suggesting a more complex effect of Bd on the immune system than simple temperature-mediated immune suppression. This study generates important baseline data for ongoing efforts to understand differences in response to Bd between susceptible and resistant frog species and the effects of chytridiomycosis in natural populations.
Project description:We used scRNA-seq to understand how CARD9 R101C remodels skin immunity and cell state in response to fungal infection in a mouse model of dermatophytosis.
Project description:The fungal skin disease chytridiomycosis has caused the devastating decline and extinction of hundreds of amphibian species globally, yet the potential for evolving resistance, and the underlying pathophysiological mechanisms remain poorly understood. We exposed 406 naïve, captive-raised alpine tree frogs (Litoria verreauxii alpina) to the aetiological agent Batrachochytrium dendrobatidis in two concurrent and controlled infection experiments. We investigated (A) survival outcomes and clinical pathogen burdens between populations and clutches, and (B) individual host tissue responses to chytridiomycosis. Here we present multiple interrelated datasets associated with these exposure experiments, including animal signalment, survival and pathogen burden of 355 animals from Experiment A, and the following datasets related to 61 animals from Experiment B: animal signalment and pathogen burden; raw RNA-Seq reads from skin, liver and spleen tissues; de novo assembled transcriptomes for each tissue type; raw gene expression data; annotation data for each gene; and raw metabolite expression data from skin and liver tissues. These data provide an extensive baseline for future analyses.
Project description:In the past century, recently emerged infectious diseases have become major drivers of species decline and extinction. Amphibian declines have occurred due to the fungal disease chytridiomycosis, which has exacerbated the conservation crisis of this taxonomic group. Biologists are beginning to understand what traits are important for susceptibility to this disease, but more work is needed to determine why some species succumb to disease while others do not. We conducted a laboratory experiment to examine how two toad species respond to infection in controlled environment. We selected two related species thought to differ in susceptibility – Bufo marinus (an invasive and putatively resistant species) and B. boreas (an endangered and putatively susceptible species). We measured infection intensity, body weight, histological changes at the site of infection, and genome-wide gene expression changes using a custom assay developed from transcriptome sequencing. Our results confirmed that the two species differ in susceptibility. The more susceptible species, B. boreas, experienced higher infection intensities, loss in body weight, more dramatic histological changes, and larger perturbations in gene expression. We found key differences in skin expression responses in multiple pathways including up-regulation of skin integrity-related genes in the resistant B. marinus. Together our results show intrinsic differences in host response between related species, which are likely to be an important factor in explaining variation in response to a deadly emerging pathogen in wild populations.