The putative flavin carrier family FlcA-C is important for Aspergillus fumigatus virulence

Aspergillus fumigatus is an opportunistic fungal pathogen and the most important species causing pulmonary fungal infections. The signaling by calcium is very important for A. fumigatus pathogenicity and it is regulated by the transcription factor CrzA. We have previously used used ChIP-seq (Chromatin Immunoprecipitation DNA sequencing) aiming to identify gene targets regulated by CrzA. We have identified among several genes regulated by calcium stress, the putative flavin transporter, flcA. This transporter belongs to a small protein family composed of FlcA, B, and C. The DflcA null mutant showed several phenotypes, such as morphological defects, increased sensitivity to calcium chelating- agent ethylene glycol tetraacetic acid (EGTA), cell wall or oxidative damaging agents and metals, representative of deficiencies in calcium signaling and iron homeostasis. Increasing calcium concentrations improved significantly the DflcA growth and conidiation, indicating that DflcA mutant has calcium insufficiency. Finally, DflcA-C mutants showed reduced flavin adenine dinucleotide (FAD) and were avirulent in a low dosemurine infection model.