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A cysteine-rich domain of the Cryptococcus neoforman s Cuf1 transcription factor is required for high copper stress sensing and fungal virulence
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A cysteine-rich domain of the Cryptococcus neoforman s Cuf1 transcription factor is required for high copper stress sensing and fungal virulence
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Journal Article
A cysteine-rich domain of the Cryptococcus neoforman s Cuf1 transcription factor is required for high copper stress sensing and fungal virulence
2026
Overview
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 to 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 motif within the copper-responsive transcription factor Cuf1 to be essential for high copper stress sensing. Mutation of this motif led to an impaired high copper stress adaptation, which did not affect the fitness of the yeast but did impact the containment and distribution of yeast cells inside the host lung.
Subject
/ Cryptococcosis - microbiology
/ Cryptococcus neoformans - drug effects
/ Cryptococcus neoformans - genetics
/ Cryptococcus neoformans - metabolism
/ Cryptococcus neoformans - pathogenicity
/ Cryptococcus neoformans - physiology
/ Cysteine
/ Fungal Proteins - metabolism
/ Gene Expression Regulation, Fungal
/ Mice
/ Transcription Factors - chemistry
/ Transcription Factors - genetics
