Abstract
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.
Highlights
Candida albicans is by far the most prevalent commensal and pathogenic Candida species
Assimilation of alternative nutrients is essential for the survival, proliferation and infection of most clinically important microbial pathogens like C. albicans in their hosts
We show that mitochondrial complex I (CI) is indispensable for proper hyphal growth and biofilm formation of C. albicans cells when mannitol, but not fermentative sugars like glucose or mannose, is used as the sole carbon source
Summary
Candida albicans is by far the most prevalent commensal and pathogenic Candida species. Once the balance is disrupted, e.g., unbalanced microbial flora after antibiotic treatment, weakened host immune response or impaired proliferation of epithelial cells, C. albicans rapidly transits from being a commensal to a pathogen and causes serious and life-threatening systemic infections [5]. Physiologically relevant carbon sources, including amino acids, fatty acids, carboxylic acids, glycerol, mannitol and N-acetylglucosamine (GlcNAc), are found at varying concentrations in different host niches and constitute major relevant nutrients for C. albicans upon infection. Lactate influences C. albicans recognition and phagocytosis by immune cells [13] These studies attest to the distinct effect of alternative carbon assimilation on the host-pathogen interaction, its contribution to virulence and commensalism. Mechanisms that C. albicans employs to cope with alternative carbon assimilation are largely unknown It remains unclear whether the regulation of carbon flexibility contributes to colonization of C. albicans in different host niches
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call