Unveiling the molecular architecture of Candida auris ribosome.

Candida auris is an emerging multidrug-resistant fungal pathogen responsible for severe healthcare-associated infections worldwide; yet, the molecular architecture of its translational apparatus remains poorly understood. Here, we present a structural and functional analysis of the C. auris ribosome. Using in-house rRNA sequencing, we found that C. auris rRNA displays substantial divergence, including the lowest 18S rRNA identity among the pathogenic Candida species examined and an unusual substitution at a functionally important nucleotide in helix h31 of the small subunit P-site region. To define the structural basis of these differences, we determined single-particle cryo-electron microscopy structures of the vacant C. auris 80S ribosome and its complexes with cycloheximide (CHX), blasticidin S (BLS), and geneticin (G418). Together with cell-free translation inhibition assays, these results establish a structural framework for understanding the C. auris ribosome and reveal how local ribosomal variation within a conserved fungal scaffold can be associated with species-specific inhibitor responses.