Molecular toolkit unlocks life cycle of the panzootic amphibian pathogen Batrachochytrium dendrobatidis.

A mphibians are facing an extinction crisis that threatens up to 50% of all species (1, 2). Uniquely, a pathogenic fungus, Batrachochytrium dendrobatidis (Bd), is now recognized as a proximate driver of these declines (3). The pathogen’s widespread global host range in 400 species of amphibian on 5 continents gives unfortunate candidacy for this being the most destructive emergence of infectious disease ever witnessed. Bd is a basal fungal lineage in the Chytridiomycota. These fungi are characteristically aquatic and flagellate, and the lack of any chytrid pathogens of vertebrates has led to the group remaining poorly characterized relative to other fungi, both at the taxonomic and molecular level. As a consequence, the mechanisms utilized by Bd to infect and cause disease in amphibians remain shrouded in mystery. The recent sequencing of two Bd genomes has created an opportunity to leverage comparative genomics and molecular biology to unlock the life cycle of this secretive fungus. The report by Rosenblum et al. (4) in a recent issue of PNAS represents the first use of this genomic information by using wholegenome arrays to compare patterns of global gene expression for two stages of Bd, the sessile sporangium and the infectious f lagellate zoospore. This new study has shown that 55% of the 9,000 genes in the Bd genome are undergoing differential expression between these two stages. Mining the predicted function of these genes by identifying similarities with genes of known function in other species (gene ontology) has provided the first clues into the higher mechanisms that orchestrate Bd growth, infection, and pathogenicity in amphibians. The acquisition of 160 fungal genomes (5) is increasingly allowing the evolutionary origin and diversification of infection-associated innovations to be mapped across the fungal pathosphere. The ecological niche that a fungus occupies is to a large extent defined by the products that it secretes, because fungi are osmotrophs and live by secreting enzymes into the environment to degrade specific polymers for nutrition. Therefore, comparing the transcriptomes of divergent lineages allows the identification of common ‘‘motifs’’ that are associated with specific ecological niches, which in the case of pathogens can translate into genes with an infection-specific role. The identification of fungalysin metallopeptidases as a gene family that has expanded to 25 members in Bd is a clue to the important function of these secreted peptides (4). Metallopeptidases have been shown to be highly up-regulated in fungi that infect human and animal skin, the Dermatophytes, accounting for up to 36% of total secreted protein extracts (6). In the dermatophytes, these proteins are associated with survival in keratin-rich tissues; skin, nails, and hair. It is well known that Bd is highly keratinophilic, surviving in the keratin-rich mouthparts of tadpoles and then infecting the keratinized stratum corneum as it is formed during metamorphosis. Therefore, that Rosenblum et al. (4) find overexpression of metalloproteases in Bd sporangia is evidence that this gene family is a key pathogenicity factor. Interestingly, only a single fungalysin was found to be more abundant in zoospores compared with sporangia. Currently, nothing is known about the mechanism that Bd zoospores use to colonize amphibian skin and to gain entrance to host cells; therefore, this gene may provide the key to unlocking this process.