An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis.
An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis.
复制标题
DOI：
10.1016/j.chom.2011.07.005
复制
发表时间：
2011-08-18
影响因子：
30.3
通讯作者：
Noble SM
中科院分区：
文献类型：
--
作者：
Chen C;Pande K;French SD;Tuch BB;Noble SM
哺乳动物的胃肠道和血流是高度不同的生物小生境，其营养物质（如铁）的浓度不同。然而，一些真菌病原微生物，如白色念珠菌，在这两种环境中都能茁壮成长。我们报道了C.白色念珠菌，控制铁的吸收，并决定其健身在这两个小生境。我们的DNA结合蛋白，调节铁的吸收，这种生物体的分析表明，两个广泛保守的铁响应转录抑制因子，Sfu1和Hap43之间的转录激活因子Sef1的进化嵌入。Sef1激活铁摄取基因，并促进血液感染的小鼠模型中的毒力，而Sfu1抑制铁摄取基因，并被证明是毒力，但促进胃肠道粘膜炎。因此，C.白色念珠菌可以在赋予对血流中的铁耗尽的抗性的遗传程序与赋予对肠道中的铁毒性的抗性的遗传程序之间交替，这可能代表了胃肠道寄生虫病原体的基本属性。
The mammalian gastrointestinal tract and bloodstream are highly disparate biological niches that differ in concentrations of nutrients such as iron. However, some commensal-pathogenic microorganisms, such as the yeast Candida albicans, thrive in both environments. We report the evolution of a transcription circuit in C. albicans that controls iron uptake and determines its fitness in both niches. Our analysis of DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved iron-responsive transcriptional repressors, Sfu1 and Hap43. Sef1 activates iron uptake genes and promotes virulence in a mouse model of bloodstream infection, whereas Sfu1 represses iron uptake genes and is dispensable for virulence but promotes gastrointestinal commensalism. Thus, C. albicans can alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut, and this may represent a fundamental attribute of gastrointestinal commensal-pathogens.
登录
查看更多内容
影响因子：
--
作者：
Forsburg, Susan L
通讯作者：
Forsburg, Susan L
影响因子：
3.4
作者：
Barelle CJ;Priest CL;Maccallum DM;Gow NA;Odds FC;Brown AJ
通讯作者：
Brown AJ
影响因子：
9.8
作者：
Jung WH;Sham A;White R;Kronstad JW
通讯作者：
Kronstad JW
影响因子：
--
作者：
Baek, Yong-Un;Li, Mingchun;Davis, Dana A.
通讯作者：
Davis, Dana A.
影响因子：
4.4
作者：
Fitzpatrick, David A.;O'Gaora, Peadar;Butler, Geraldine
通讯作者：
Butler, Geraldine