Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Cell Host Microbe. 2013 Nov 13;14(5):499-509. doi: 10.1016/j.chom.2013.10.008.
Candida albicans reversibly switches between yeast and hyphal morphologies, with hyphae being associated with virulence. Hyphal initiation and maintenance depend 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.
白色念珠菌可在酵母和菌丝两种形态之间可逆转换，而菌丝形态与毒力相关。菌丝的起始和维持依赖于对宿主环境的感知。体外培养的菌丝维持需要对菌丝特异性基因启动子进行染色质重塑，尽管破坏染色质重塑并不影响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联合作用（而非单独作用）维持了菌丝的伸长，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。菌丝特异性基因的转录激活因子 Ume6 通过受缺氧抑制的脯氨酰羟化酶家族成员 Ofd1 的调控以及一个尚未确定的感知高二氧化碳的通路来稳定。体内毒力和菌丝伸长只有在平行作用的 Ume6 稳定和染色质重塑途径都被阻断时才会减弱。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。
