Homeostatic control of an iron repressor in a GI tract resident

The transition metal iron plays a crucial role in living cells. However, high levels of iron are potentially toxic through the production of reactive oxygen species (ROS), serving as a deterrent to the commensal fungus Candida albicans for colonization in the iron-rich gastrointestinal tract. We observe that the mutant lacking an iron-responsive transcription factor Hap43 is hyper-fit for colonization in murine gut. We demonstrate that high iron specifically triggers multiple post-translational modifications and proteasomal degradation of Hap43, a vital process guaranteeing the precision of intestinal ROS detoxification. Reduced levels of Hap43 de-repress the expression of antioxidant genes and therefore alleviate the deleterious ROS derived from iron metabolism. Our data reveal that Hap43 functions as a negative regulator for oxidative stress adaptation of C. albicans to gut colonization and thereby provide a new insight into understanding the interplay between iron homeostasis and fungal commensalism.

Automated summary

The transition metal iron is important in living cells, but high levels can be toxic. A new study finds that a mutant lacking the iron-responsive transcription factor Hap43 is better able to colonize the gastrointestinal tract. The researchers demonstrate that high iron triggers post-translational modifications and degradation of Hap43, leading to reduced levels and increased expression of antioxidant genes. This study provides insight into the interplay between iron homeostasis and fungal colonization in the gut.