First Report of Candida auris Candidemia in Portugal: Genomic Characterisation and Antifungal Resistance-Associated Genes Analysis

<i>Candida auris</i> has emerged as a global public health threat due to its high mortality rates, multidrug resistance, and rapid transmission in healthcare settings. This study reports the first documented cases of <i>C. auris</i> candidemia in Portugal, comprising eight isolates from candidemia and colonised patients admitted to a major hospital in northern Portugal in 2023. Whole-genome sequencing (WGS) was performed to determine the phylogenetic relationships of the isolates, which were classified as belonging to Clade I. Genome sequencing also enabled the detection of missense mutations in antifungal resistance genes, which were correlated with antifungal susceptibility profiles determined according to EUCAST (European Committee on Antimicrobial Susceptibility Test) protocols and guidelines. All isolates exhibited resistance to fluconazole and amphotericin B according to the recently established EUCAST epidemiological cut-offs (ECOFFs). Most of the isolates showed a resistant phenotype to anidulafungin and micafungin. All isolates were resistant to caspofungin. Missense mutations identified included Y132F in <i>ERG11</i>, E709D in <i>CDR1</i>, A583S in <i>TAC1b</i>, K52N and E1464K in <i>SNQ2</i>, K74E in <i>CIS2</i>, M192I in <i>ERG4</i>, a novel mutation S237T in <i>CRZ1</i>, and variants in <i>GCN5</i>, a gene involved in chromatin remodelling and stress-response regulation. Identifying known and novel mutations highlights the evolution of antifungal resistance mechanisms in <i>C. auris</i>. These findings underscore the need for further research to understand <i>C. auris</i> resistance pathways and to guide effective clinical management strategies.