Synergistic regulation of hyphal elongation by hypoxia, CO(2), and nutrient conditions controls the virulence of Candida albicans.
Synergistic regulation of hyphal elongation by hypoxia, CO(2), and nutrient conditions controls the virulence of Candida albicans.
复制标题
DOI：
10.1016/j.chom.2013.10.008
复制
发表时间：
2013-11-13
影响因子：
30.3
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Lu Y;Su C;Solis NV;Filler SG;Liu H
白色念珠菌在酵母和菌丝形态之间可逆地转换，其中菌丝与毒力相关。菌丝的启动和维持取决于宿主环境的感知。体外菌丝维持需要菌丝特异性基因启动子的染色质重塑，尽管破坏染色质重塑不会破坏白色念珠菌在侵袭性感染期间的菌丝伸长和毒力。我们发现，缺氧和高二氧化碳的组合（但单独的条件除外）可以维持菌丝伸长，即使在缺乏营养响应染色质重塑途径的突变体中也是如此。 Ume6 是菌丝特异性基因的转录激活因子，通过 Ofd1（一种受缺氧抑制的脯氨酰羟化酶家族成员）和感知高 CO2 的未知途径的调节来稳定。仅当同时作用的 Ume6 稳定和染色质重塑途径均被阻断时，体内毒力和菌丝伸长才会减弱。冗余信号通路的进化使白色念珠菌能够适应不同的宿主环境，这可能解释了这种共生菌作为病原体的成功。
Candida albicans reversibly switches between yeast and hyphal morphologies, with hyphae being associated with virulence. Hyphal initiation and maintenance depends on host environment sensing. Hyphal maintenance in vitro requires chromatin remodeling of hypha-specific gene promoters, although disrupting chromatin-remodeling does not disrupt C. albicans hyphal elongation and virulence during invasive infection. We find that the combination of hypoxia and high CO2, but neither condition alone, maintains hyphal elongation, even in mutants lacking the nutrient responsive chromatin-remodeling pathway. Ume6, the transcriptional activator of hypha-specific genes is stabilized via regulation by Ofd1, a prolyl hydroxylase family member inhibited by hypoxia, and by an uncharacterized pathway that senses high CO2. Virulence and hyphal elongation in vivo are attenuated only when the parallelly acting Ume6 stabilization and chromatin-remodeling pathways are both blocked. The evolution of redundant signaling pathways allowing C. albicans to adapt to varied host environments may explain this commensal's success as a pathogen.
登录
查看更多内容
影响因子：
30.3
作者：
Chen C;Pande K;French SD;Tuch BB;Noble SM
通讯作者：
Noble SM
影响因子：
6.7
作者：
Cottier F;Raymond M;Kurzai O;Bolstad M;Leewattanapasuk W;Jiménez-López C;Lorenz MC;Sanglard D;Váchová L;Pavelka N;Palková Z;Mühlschlegel FA
通讯作者：
Mühlschlegel FA
影响因子：
64.5
作者：
Lo, HJ;Kohler, JR;Fink, GR
通讯作者：
Fink, GR
影响因子：
4.9
作者：
Dumitru, R;Hornby, JM;Nickerson, KW
通讯作者：
Nickerson, KW
影响因子：
3.3
作者：
Lu, Yang;Su, Chang;Chen, Jiangye
通讯作者：
Chen, Jiangye