The adaptive response to iron involves changes in energetic strategies in the pathogen Candida albicans

Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to systemic diseases known as candidiasis. Its ability to grow in different morphological forms, such as yeasts or filamentous hyphae, contributes to its survival in diverse microenvironments. Iron uptake has been associated with virulence, and C. albicans has developed elaborate strategies for acquiring iron from its host. In this work, we analyze the metabolic changes in response to changes in iron content in the growth medium and compare C. albicans adaptation to the presence or absence of iron. Functional and morphological studies, correlated to a quantitative proteomic analysis, were performed to assess the specific pathways underlying the response to iron, both in the yeast and filamentous forms. Overall, the results show that the adaptive response to iron is associated with a metabolic remodeling affecting the energetic pathways of the pathogen. This includes changes in the thiol‐dependent redox status, the activity of key mitochondrial enzymes and the respiratory chain. Iron deficiency stimulates bioenergetic pathways, whereas iron‐rich condition is associated with greater biosynthetic needs, particularly in filamentous forms. Moreover, we found that C. albicans yeast cells have an extraordinary capability to adapt to changes in environmental conditions. We analyze here the adaptive response of Candida albicans cells to changes in the iron content of the culture environment. This response includes changes in intracellular redox status and the reorientation of metabolic pathways, as shown by label‐free analyses and biochemical measurements. We found that iron deficiency stimulated the TCA cycle, mitochondrial respiratory chain, and ATP production, to compensate for cellular stress, to maintain normal levels of ATP, and to ensure cell survival. Conversely, an increase of iron is associated with biosynthetic needs, especially in filamentous forms.