Coordinated responses to host-derived stresses in C. neoformans

摘要 尽管目前已有有效的抗真菌药物，但侵袭性真菌感染仍然存在。 疾病和死亡的高流行原因，特别是在我们最脆弱的缺陷患者中 免疫系统。艾滋病、器官移植和更激进的癌症治疗都有助于 不断扩大的患者群体，他们面临这些严重感染的风险。未来的发展方向 传染病的治疗将越来越多地涉及识别特定于微生物的细胞过程。 这可以成为干预的目标。 在这项计划中，我们将研究人类真菌病原体的中心信号通路。 在感染环境中诱导的新生隐球菌(CN)。我们开始研究 CN中真菌特异的Rim信号通路作为表面被膜表达和真菌的调节 细胞健康。利用互补的转录、蛋白质组和微生物遗传技术，我们已经 这种真菌病原体中明确的环状依赖细胞事件，使微生物能够快速适应 主机环境。这些适应中的许多都是专门针对感染者的PH值而发生的 主持人。因此，我们的研究不仅涉及微生物的发病机制，而且还探索了 真核细胞感知和响应这一重要环境条件的方式。

SUMMARY Although potent antifungal agents are currently available, invasive fungal infections remain highly prevalent causes of disease and death, especially in our most vulnerable patients with defective immune systems. AIDS, organ transplantation, and more aggressive cancer treatments all contribute to ever-expanding patient groups who are at risk for these serious infections. Future directions in the treatment of infectious diseases will increasingly involve identifying microbe-specific cellular processes that can be targeted for intervention. In this proposal, we will study central signaling pathways in the human fungal pathogen Cryptococcus neoformans (Cn) that are induced in the setting of infection. We began studying the fungal-specific Rim signaling pathway in Cn as a regulator of surface capsule expression and fungal cell fitness. Using complementary transcriptomic, proteomic, and microbial genetic techniques, we have defined Rim-dependent cellular events in this fungal pathogen that allow rapid microbial adaptation to the host environment. Many of these adaptations occur specifically in response to the pH of the infected host. Therefore, our studies not only address microbial pathogenesis, but they also explore central ways in which eukaryotic cells sense and respond to this important environmental condition.