PDF(Pubmed)
Abstract：
Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival.
Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions.
Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants.
Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions.
Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants.
摘要：
真菌感染影响超过25%的全球人口。对于机会性真菌病原体，新生隐球菌,感染导致隐球菌病。在主人面前,疾病是通过阐述复杂的毒力决定因素来实现的，包括多糖胶囊，黑色素,耐热性,和胞外酶。相反，宿主通过调节和螯合过渡金属来保护自己免受真菌入侵(例如，铁,锌，铜)对微生物生长和生存很重要。
这里,我们通过基于质谱的定量蛋白质组学研究了锌利用率和真菌毒力之间的复杂关系.我们观察到核心蛋白质组以及独特的锌调节蛋白质水平特征，表明从锌充足条件下的运输和离子结合向锌限制条件下的转录和金属获取转移。此外,我们揭示了锌可用性之间的一种新的联系，耐热性,以及通过在充足的条件下检测分泌组中的Wos2直系同源物的胶囊和黑色素产生。
总的来说，我们提供了新的生物学见解，在受调节的锌条件下，在细胞重塑的C。新生梭菌的蛋白质水平，并揭示了锌稳态和真菌毒力决定子之间的新联系。
这里,我们通过基于质谱的定量蛋白质组学研究了锌利用率和真菌毒力之间的复杂关系.我们观察到核心蛋白质组以及独特的锌调节蛋白质水平特征，表明从锌充足条件下的运输和离子结合向锌限制条件下的转录和金属获取转移。此外,我们揭示了锌可用性之间的一种新的联系，耐热性,以及通过在充足的条件下检测分泌组中的Wos2直系同源物的胶囊和黑色素产生。
总的来说，我们提供了新的生物学见解，在受调节的锌条件下，在细胞重塑的C。新生梭菌的蛋白质水平，并揭示了锌稳态和真菌毒力决定子之间的新联系。
