Davis D, Edwards J E, Mitchell A P, Ibrahim A S
Department of Microbiology, Columbia University, New York, New York 10032, USA.
Infect Immun. 2000 Oct;68(10):5953-9. doi: 10.1128/IAI.68.10.5953-5959.2000.
The ability of Candida albicans to respond to diverse environments is critical for its success as a pathogen. The RIM101 pathway controls gene expression and the yeast-to-hyphal transition in C. albicans in response to changes in environmental pH in vitro. In this study, we found that the RIM101 pathway is necessary in vivo for pathogenesis. First, we show that rim101(-)/rim101(-) and rim8(-)/rim8(-) mutants have a significant reduction in virulence using the mouse model of hematogenously disseminated systemic candidiasis. Second, these mutants show a marked reduction in kidney pathology. Third, the rim101(-)/rim101(-) and rim8(-)/rim8(-) mutants show defects in the ability to damage endothelial cells in situ. Finally, we show that an activated allele of RIM101, RIM101-405, is a suppressor of the rim8(-) mutation in vivo as it rescues the virulence, histological, and endothelial damage defects of the rim8(-)/rim8(-) mutant. These results demonstrate that the RIM101 pathway is required for C. albicans virulence in vivo and that the function of Rim8p in pathogenesis is to activate Rim101p.
白色念珠菌对多种环境作出反应的能力对其作为病原体的成功至关重要。RIM101途径可控制基因表达以及白色念珠菌在体外对环境pH变化作出反应时的酵母-菌丝转变。在本研究中，我们发现RIM101途径在体内对发病机制是必需的。首先，我们利用血源性播散性系统性念珠菌病小鼠模型表明，rim101(-)/rim101(-)和rim8(-)/rim8(-)突变体的毒力显著降低。其次，这些突变体的肾脏病理学表现明显减轻。第三，rim101(-)/rim101(-)和rim8(-)/rim8(-)突变体在原位损伤内皮细胞的能力方面存在缺陷。最后，我们表明RIM101的一个激活等位基因RIM101-405在体内是rim8(-)突变的一个抑制因子，因为它挽救了rim8(-)/rim8(-)突变体的毒力、组织学和内皮损伤缺陷。这些结果表明，RIM101途径是白色念珠菌在体内致病所必需的，并且Rim8p在发病机制中的功能是激活Rim101p。
