P480 A novel zincophore locus in Candida auris?

POSTER SESSION 1, SEPTEMBER 21, 2022, 12:30 PM - 1:30 PM: Candida auris is an emerging multidrug-resistant human fungal pathogen that is spreading rapidly across the world and is associated with hospital-acquired invasive infections with high mortality rates. Whilst previous studies have focused on understanding the basic biology and drug resistance mechanisms of C. auris, nothing is known about the strategies underlying trace metal acquisition. Trace metals like zinc are known to be crucial for numerous biological functions across all kingdoms of life. Thus, in this study, we aimed to characterize the zinc uptake mechanisms of C. auris and determine their role in virulence. We compared the ability of C. auris to grow in zinc-restricted conditions with other pathogenic fungi belonging to the CTG and WGD clade. Regardless of the clade, we found that C. auris has a striking ability to grow under extreme zinc-limiting conditions when compared with other human pathogenic fungi. : Other fungi have been demonstrated to scavenge zinc via a zincophore locus, encoding a secreted zinc-binding protein Pra1 and its cognate receptor, Zrt101. However, in silico analysis of C. auris revealed that this species has undergone a rearrangement of the locus. The canonical zincophore gene PRA1 has translocated to another chromosome and the extracellular zinc-binding domain of the Zrt101 receptor has undergone an inverted duplication generating a novel putative zincophore. : Our qRT-PCR analysis demonstrated that both PRA1 and the novel zincophore genes were upregulated in response to neutral pH and zinc-restriction. Protein supernatant from C. auris strains also showed high zinc binding activity. Furthermore, we have generated mutants lacking the novel zincophore gene in C. auris by CRISPR/Cas9 and found that these deletion mutants exhibited perturbed growth under zinc limitation. Together our observations suggest that C. auris has evolved a unique zinc acquisition strategy from the environment and the host.