A Novel Virulence Phenotype Rapidly Assesses Fungal Pathogenesis in Healthy and Immunocompromised Hosts.

The yeast is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While is the predominant species isolated in the human gastrointestinal mycobiome and is implicated in fungal infection, infections due to non-albicans species are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. Here, we utilize the nematode as a perspicuous and efficient model host system to study fungal infections of pathogens. We find that, in addition to reducing lifetime host survival, exposure to results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in hosts compromised for innate immune function and detected increased early mortality, reduced brood sizes, and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds, we reveal the pathogen potential in non-albicans species. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence. Opportunistic pathogens are commensals capable of causing disease and are serious threats to human health. It is critical to understand the mechanisms and host contexts under which opportunistic pathogens become virulent. In this work, we present a novel assay to quickly and quantitatively measure pathogen virulence in healthy and immunocompromised nematode hosts. We found that species, one of the most prominent fungal opportunistic pathogens of humans, decrease host fitness by reducing survival and impacting host reproduction. Most importantly, by measuring virulence in hosts that have intact or compromised immune function, we can reveal the pathogenic potential of opportunistic fungal pathogens.