Transcriptomic and Proteomic Approaches to Finding Novel Diagnostic and Immunogenic Candidates in .

pneumonia is the most common serious opportunistic infection in patients with HIV/AIDS. Furthermore, pneumonia is a feared complication of the immunosuppressive drug regimens used to treat autoimmunity, malignancy, and posttransplantation rejection. With an increasing at-risk population, there is a strong need for novel approaches to discover diagnostic and vaccine targets. There are multiple challenges to finding these targets, however. First, has a largely unannotated genome. To address this, we evaluated each protein encoded within the genome by comparisons to proteins encoded within the genomes of other fungi using NCBI BLAST. Second, relies on a multiphasic life cycle, as both the transmissible form (the ascus) and the replicative form (the trophozoite [troph]) reside within the alveolar space of the host. To that end, we purified asci and trophs from and utilized transcriptomics to identify differentially regulated genes. Two such genes, and , are differentially regulated in the ascus and the troph, respectively, and can be utilized to characterize the state of the life cycle , encoding a β-1,3-glucan synthase with a large extracellular domain previously identified using surface proteomics, was more highly expressed on the ascus form of GSC-1 ectodomain immunization generated a strong antibody response that demonstrated the ability to recognize the surface of the asci. GSC-1 ectodomain immunization was also capable of reducing ascus burden following primary challenge with Finally, mice immunized with the GSC-1 ectodomain had limited fungal burden following natural transmission of using a cohousing model. The current report enhances our understanding of biology in a number of ways. First, the current study provided a preliminary annotation of the genome, addressing a long-standing issue in the field. Second, this study validated two novel transcripts enriched in the two predominant life forms of These findings allow better characterization of the life cycle and could be valuable diagnostic tools. Furthermore, this study outlined a novel pipeline of -omics techniques capable of revealing novel antigens (e.g., GSC-1) for the development of vaccines against .