Pathogenic Fungal Sensing and Responses to Stressful Host Environments

Despite the ubiquity of fungi in nature, only a small fraction are pathogenic to humans, and the majority of these fungi are opportunistic and affect immunocompromised individuals. In general, pathogen emergence is restricted by the ability of fungi to sense and withstand human host environmental cues and stresses. These stress responses in fungi involve immediate survival reactions as well as long-term adaptations. Additionally, some opportunistic pathogenic behavior suggests that virulence traits evolved for environmental survival, a concept known as exaptation. This review covers recent advances in examining fungal responses to host environments and focuses on stress pathways including HOG (high osmolarity glycerol) and CWI (cell wall integrity), thermotolerance mechanisms, CO₂ and oxygen sensing, nutrient and metal stresses, pH adaptation, and antimicrobial defenses. By focusing on both conserved and specialized responses, we highlight the critical role of stress adaptation in pathogenicity and potential avenues for further research and therapeutic intervention.