Havel Virginia E, Wool Nathan K, Ayad David, Downey Kurtis M, Wilson Christabel F, Larsen Peter, Djordjevic Julianne T, Panepinto John C
Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Eukaryot Cell. 2011 Jul;10(7):895-901. doi: 10.1128/EC.00006-11. Epub 2011 May 20.
Adaptation to host temperature is a prerequisite for any pathogen capable of causing deep infection in humans. Our previous studies demonstrated that a Cryptococcus neoformans ccr4Δ mutant lacking the major deadenylase involved in regulated mRNA decay was defective in host temperature adaptation and therefore virulence. In this study, the ccr4Δ mutant was found to exhibit characteristics of chronic unfolded-protein response (UPR) engagement in both the gene expression profile and phenotype. We demonstrate that host temperature adaptation in C. neoformans is accompanied by transient induction of the endoplasmic reticulum (ER) stress response and that Ccr4-dependent posttranscriptional gene regulation contributes to resolution of ER stress during host temperature adaptation.
适应宿主温度是任何能够在人类体内引起深部感染的病原体的先决条件。我们之前的研究表明，新型隐球菌ccr4Δ突变体缺乏参与调控mRNA衰变的主要去腺苷酸化酶，在宿主温度适应方面存在缺陷，因此毒力也有缺陷。在本研究中，发现ccr4Δ突变体在基因表达谱和表型上均表现出慢性未折叠蛋白反应（UPR）参与的特征。我们证明，新型隐球菌的宿主温度适应伴随着内质网（ER）应激反应的短暂诱导，并且Ccr4依赖的转录后基因调控有助于在宿主温度适应过程中解决ER应激。
