3 years ago

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

Yongmin He, Xiangjiang Zhan, Xiaoyu Yu, Xiaoqing Chen, Shanshan Li, Xianwei Wu, Wenjuan Wu, Xinhua Huang, Changbin Chen, Ning Gao, Yuanyuan Wang, Jianhua Wu, Lida Niu, Yinhe Mao, Dongsheng Zhou

by Xinhua Huang, Xiaoqing Chen, Yongmin He, Xiaoyu Yu, Shanshan Li, Ning Gao, Lida Niu, Yinhe Mao, Yuanyuan Wang, Xianwei Wu, Wenjuan Wu, Jianhua Wu, Dongsheng Zhou, Xiangjiang Zhan, Changbin Chen

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.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.ppat.1006414

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