Homeostatic control of an iron repressor in a GI tract resident.
Yuanyuan WangYinhe MaoXiaoqing ChenXinhuang HuangZhongyi JiangKaiyan YangLixing TianTong JiangYun ZouXiaoyuan MaChaoyue XuZili ZhouXianwei WuLei PanHuaping LiangLin ZhongChangbin ChenPublished in: eLife (2023)
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 (GI) 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 (PTMs) 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.
Keyphrases
- reactive oxygen species
- iron deficiency
- candida albicans
- oxidative stress
- transcription factor
- living cells
- dna damage
- cell death
- electronic health record
- machine learning
- genome wide
- dna methylation
- staphylococcus aureus
- long non coding rna
- fluorescent probe
- heat shock
- quality improvement
- anti inflammatory
- transition metal
- binding protein
- heat stress