IDENTIFICATION OF A β-ARRESTIN INVOLVED IN THE FUNGAL HEME-IRON ACQUISITION PATHWAY

Candida albicans is a human commensal microorganism that has the ability to adapt and proliferate in different host environments such as the skin, nails and gastrointestinal tract. In addition, C. albicans is able to cause deep-seated, life-threathening infections in an immunocompromised host. In the human host, free iron is very scarce and therefore, iron acquisition is an important virulence factor for pathogenic microbes. To overcome iron starvation in the host environment, many pathogens can utilize host hemoglobin as iron source. Some fungal pathogens, including C. albicans, deploy a network of extracellular CFEM proteins that extract heme from hemoglobin, transfer it from one CFEM protein to the next across the cell wall and internalize the extracted heme via the endocytic pathway. In order to identify the components of the endocytic pathway required for heme internalization, we screened a library of C. albicans mutants deleted for one allele of a given gene, and with the second allele under TEToff control. We identified RIM8, the sole b-arrestin homolog in the C. albicans genome, as a gene involved in heme-iron utilization. b-arrestins are involved in ubiquitin-mediated internalization of transmembrane channels and receptors. Deletion of RIM8 results in disturbed trafficking of the putative heme receptor Hut1, suggesting a direct role of Rim8 in the heme internalization pathway.