Mus musculus (A/J) lung infection with Cryptococcus neoformans (serotype A) clinical isolates

To predict the outcomes of disseminated fungal disease, a deeper understanding of host-pathogen interactions at the site of infection is needed to identify targets for clinical intervention and diagnostic development. Cryptococcus neoformans is the causative agent of cryptococcosis, the largest infectious killer of individuals living with HIV. Cryptococcal infection begins in the lungs, with loss of immunological control leading to disseminated central nervous system disease and death. Using advanced mass spectrometry-based proteomic techniques, in vivo infection models, and patient-derived clinical strains, we explored the proteomic profiles of C. neoformans infections related to differences in strain virulence. Our findings reveal the non-lethal latent infection produces a proteomic response that drastically differs from those caused by lethal infections, and that the proteomic profiles of typical and hypervirulent infections are surprisingly similar despite differences in time-to-death.