Mitochondrial complex I bridges a connection between regulation of carbon flexibility and gastrointestinal commensalism in the human fungal pathogen Candida albicans

PLoS Pathogens

Lida Niu¹  Yongmin He²  Yuanyuan Wang³  Xiangjiang Zhan³  Shanshan Li⁴  Dongsheng Zhou⁴  Changbin Chen⁵  Xianwei Wu⁶  Xiaoyu Yu⁶  Xinhua Huang⁶  Ning Gao⁶  Xiaoqing Chen⁶  Jianhua Wu⁶  Yinhe Mao⁶  Wenjuan Wu⁶ 

[1] College of Life Science, Shanghai Normal University, Shanghai, China;College of Life Science, Shanghai University, Shanghai, China;Department of Dermatology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China;Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of medicine, Shanghai, China;State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China;Unit of Pathogenic Fungal Infection & Host Immunity, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China

关键词: C;    ida albicans;    Mannitol;    Biofilms;    Glucose;    Mannose;    Glycerol;    Commensalism;    Phosphorylation;   

DOI  :  10.1371/journal.ppat.1006414

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Efficient assimilation of alternative carbon sources in glucose-limited host niches is critical for colonization of Candida albicans, a commensal yeast that frequently causes opportunistic infection in human. C. albicans evolved mechanistically to regulate alternative carbon assimilation for the promotion of fungal growth and commensalism in mammalian hosts. However, this highly adaptive mechanism that C. albicans employs to cope with alternative carbon assimilation has yet to be clearly understood. Here we identified a novel role of C. albicans mitochondrial complex I (CI) in regulating assimilation of alternative carbon sources such as mannitol. Our data demonstrate that CI dysfunction by deleting the subunit Nuo2 decreases the level of NAD+, downregulates the NAD+-dependent mannitol dehydrogenase activity, and consequently inhibits hyphal growth and biofilm formation in conditions when the carbon source is mannitol, but not fermentative sugars like glucose. Mannitol-dependent morphogenesis is controlled by a ROS-induced signaling pathway involving Hog1 activation and Brg1 repression. In vivo studies show that nuo2Δ/Δ mutant cells are severely compromised in gastrointestinal colonization and the defect can be rescued by a glucose-rich diet. Thus, our findings unravel a mechanism by which C. albicans regulates carbon flexibility and commensalism. Alternative carbon assimilation might represent a fitness advantage for commensal fungi in successful colonization of host niches.

【 授权许可】

CC BY