Systematic analysis reveals an Mln1-dependent trade-off between metabolic flexibility and thermotolerance in Cryptococcus neoformans

In Cryptococcus neoformans, MLN1 loss impairs carbon-starvation gene expression and growth on non-preferred carbon sources, especially trehalose, while increasing thermotolerance.

• Why it matters: Pathogens must coordinate temperature and nutrient responses during infection, but how specific transcription factors link metabolic flexibility to stress resistance is unclear.
• What they did: The authors integrated in vivo expression profiling with signature-tagged mutagenesis infectivity data to prioritize 24 transcription factors, then dissected MLN1 regulation by Mig1 and tested mln1{Delta} phenotypes under carbon stress and heat.
• The result: mln1{Delta} cells accumulated more intracellular trehalose and showed enhanced thermotolerance, but had reduced melanization, titan cell formation, virulence in Drosophila, and brain fungal burden in mice.

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