Abstract
Copper is an essential micronutrient required for survival in all kingdoms of life as it is used as a catalytic cofactor for many essential processes in the cell. In turn, this reactivity of copper ions makes elevated levels of free copper toxic for the cell. This dual nature of copper-essential for life but toxic at elevated levels- is used by our innate immune system in a process called nutritional immunity to combat and kill invading pathogens. In this work we explore how the fungal human pathogen Cryptococcus neoformans senses high copper stress, a copper microenvironment encountered within the host lung. We identified a specific cysteine-rich region within the copper responsive transcription factor Cuf1 to be essential for high copper stress sensing. Mutation of this region led to an impaired high copper stress adaptation, which did not affect fitness of the yeast but did impact immune recognition and inflammation inside the host lung.
Published Version
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