Genomic landscape of Candidozyma auris in Italy, 2019 to 2025: emerging diversity of clade I sub-lineages associated with inter-facility transmission and cross-border transfers.

Abstract

BACKGROUNDCandidozyma auris is a fungal pathogen of major concern, that frequently exhibits multidrug resistance and causes healthcare-related outbreaks worldwide. Italy experienced a large nosocomial outbreak in early 2020, with subsequent sporadic cases or small clusters in different regions.AIMTo provide an overview of the C. auris population structure, genomic diversity, and spread in Italy.METHODSGenome sequences from Italian C. auris isolates (n = 68) were obtained either from public databases, or by whole-genome sequencing of available isolates (n = 17) from previously uncharacterised and/or recently emerged (2025) cases. The sequence dataset was complemented with whole genome sequences of international isolates (n = 139) to conduct a global phylogenetic analysis based on core-genome single nucleotide polymorphisms. Genetic mutations associated with antifungal resistance were investigated.RESULTSAll Italian isolates belonged to clade I (South Asian) but were interspersed among different subclades. Subclade Ic isolates were of a single lineage, characterised by the HMG1P238H mutation. This lineage spread over four regions. Subclade Ib members were more diverse, and associated with local or imported single cases, as well as nosocomial clusters following sporadic, independent C. auris introductions from countries in southern Europe. A putative new subclade (Id) was identified, involving isolates from Italy and an eastern European country. Subclades Ib-c-d exhibited lineage-specific genetic signatures in antifungal-resistance-associated loci (CDR1, ERG11, TAC1B).CONCLUSIONSIn Italy, C. auris strains form a complex population, resulting from emergence or evolution of clade I sub-lineages following, in some instances, sporadic introductions from other European countries. Strengthened screening protocols remain essential for inter-facility transfers and for patients with prior healthcare exposure abroad.