Unveiling Host-Pathogen Interactions in Coccidioides Respiratory Infection: Hypothetical Protein Annotation and Immune Dynamics 4401

Abstract Description Coccidioides species are soil-dwelling fungi that cause a severe respiratory disease ranked as a significant fungal pathogen by WHO. With infections expected to rise, there is an urgent need to understand the host immunity and fungal biology. This study explores early immunological responses to Coccidioides, focusing on the link between fungal proteins using bioinformatics and potential immunological outcomes using mouse infection models. Coccidioides genome contains substantial uncharacterized hypothetical proteins, which may drive pathogenicity, immune evasion, and host modulation. We characterize and functionally annotate Coccidioides immitis hypothetical protein sequences, revealing ∼9k high-quality proteins based on homology scoring, conserved domains, subcellular localization, and physicochemical properties revealing potential roles in disease and pathogenicity. We correlate these data with in-vivo Coccidioides infection single-cell RNA sequencing data demonstrating PD-L1 expressing neutrophils and contact-dependent Spp1+ macrophages dominant the early response. We next compare Coccidioides with known respiratory fungal virulence factors, identifying 300 Coccidioides unannotated proteases for structural homology analysis and prediction of host immune pathway interactions. These data elucidate the early dynamics of host immune interactions with Coccidioides, providing a foundation for further understanding of host-pathogen interactions in fungal respiratory infection. Funding Sources Supported by NIH/NIAID R15AI174173 and GEM Graduate Fellowship. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)