Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway

Area of Science:

• Mycology
• Medical Microbiology
• Molecular Biology

Background:

• Candida albicans is a human fungal commensal causing mucosal and systemic infections.
• Fungal adaptation to host conditions, including nutrient availability, is crucial for virulence.
• Lactate, a product of microbiota, affects C. albicans drug resistance and immune evasion.

Purpose of the Study:

• To investigate the metabolic rewiring of C. albicans upon exposure to lactate.
• To understand the impact of lactate on iron homeostasis and virulence factors.

Main Methods:

• Genome-wide transcriptomic analysis of C. albicans.
• Gene expression profiling under lactate exposure at pH 5.
• Assessment of iron uptake and intracellular iron accumulation.
• Growth assays with iron-transport defective mutants.

Main Results:

• Lactate exposure downregulates genes in the reductive iron uptake pathway.
• Lactate promotes intracellular iron accumulation in C. albicans.
• Lactate enhances the growth of iron-transport defective C. albicans under iron limitation.
• Lactate-induced iron assimilation is independent of protein kinase A (PKA) signaling.

Conclusions:

• Lactate significantly impacts C. albicans iron homeostasis.
• Metabolic rewiring by lactate influences fungal virulence in the host.
• Understanding lactate's role in iron metabolism provides insights into nutritional immunity strategies.