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PubMed2026

Resistance gene mutations and phylogenetic relationships in Candidozyma auris isolates from Russia.

INTRODUCTION: Candidozyma auris is an emerging healthcare-associated fungal pathogen with a high propensity for nosocomial transmission and development of antifungal resistance. This study aimed to identify resistance-associated genomic variants and characterize the phylogenetic structure of clinical C. auris isolates circulating in Russia. METHODS: We analyzed 82 isolates collected between 2017 and 2023 from 18 hospitals in the Northwestern and Central Federal Districts of the Russian Federation. Antifungal susceptibility testing was combined with whole-genome sequencing, targeted FCY2 sequencing, and comparative phylogenomic analysis using publicly available international genomes. RESULTS: All isolates analyzed in this study belonged to clade I and showed a highly conserved profile of elevated azole MICs. The consistent detection of ERG11 (K143R), TAC1B (A640V), and CDR1 (V704L) suggests that reduced azole susceptibility in this population is associated with both target-gene alteration and efflux-mediated mechanisms. All isolates remained susceptible to echinocandins in vitro, and no resistance-conferring mutations were detected in FKS1, consistent with the absence of an echinocandin-resistant phenotype. Decreased susceptibility to flucytosine was mainly associated with the FCY2 (L383*) nonsense mutation, which was confirmed by targeted Sanger sequencing in additional isolates. Phylogenomic reconstruction showed that the Russian isolates represented a restricted segment of global clade I diversity and revealed two major geographically structured lineages corresponding to two large metropolitan areas in European Russia. DISCUSSION: The distribution of closely related isolates across hospitals supports local persistence and inter-hospital dissemination of genetically related strains. These findings provide important insights into the molecular epidemiology, antifungal resistance mechanisms, and transmission dynamics of C. auris in Russia.

Phylogeny↗

PubMed2026

Clade-dependent antifungal resistance and susceptibility in Candidozyma auris: A global scoping review.

BACKGROUND: Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant fungal pathogen that has spread globally since its first identification in 2009 and is now classified as a critical-priority pathogen by the World Health Organization. Distinct genetic clades are associated with variations in geographic distribution, antifungal susceptibility, and resistance mechanisms; however, clade-specific evidence remains fragmented. AIMS: To systematically map global evidence on clade diversity, antifungal susceptibility patterns, resistance mechanisms, and clinical implications of C. auris. METHODS: A scoping review was conducted following PRISMA-ScR guidelines. Peer-reviewed primary studies published between 2009 and September 2025 were included if they reported clade attribution and antifungal susceptibility or resistance data. PubMed/MEDLINE, Scopus, and Web of Science were searched. Two reviewers independently screened studies and extracted data using a standardized form. RESULTS: Of 2050 records identified, 105 studies met inclusion criteria, representing 29 countries and diverse study designs. Whole-genome sequencing was the most common typing method. Antifungal susceptibility varied substantially across clades. High fluconazole resistance was consistently reported (MIC 4 to >256μg/mL). Echinocandins generally retained activity, although reduced susceptibility associated with FKS1 mutations was observed. Resistance mechanisms primarily involved mutations in ERG11, FKS1, and efflux-related genes. Studies also reported challenges in healthcare-associated transmission, environmental persistence, and diagnostic misidentification. CONCLUSIONS: C. auris exhibits marked clade-dependent variability in antifungal susceptibility and resistance mechanisms. These findings support the need for clade-informed interpretation of susceptibility data, standardized surveillance, improved diagnostics, and development of novel antifungal therapies.

Antifungal Agents↗

PubMed2026

Microbe Profile: Candidozyma auris: an emergent and resilient yeast and new antifungal strategies.

Candidozyma auris is an emerging opportunistic yeast that is important because of its multidrug resistance, persistence in healthcare environments and ability to cause outbreaks. Since its discovery in 2009 in Japan, it has rapidly spread worldwide and is now recognized as a major global public health threat and was recognized by the World Health Organization (WHO) in 2022 as a critical priority fungal pathogen. Distinct phylogeographic clades demonstrate simultaneous emergence on different continents, suggesting ecological or environmental triggers. Clinical management is complicated by frequent resistance to fluconazole, reduced susceptibility to amphotericin B and echinocandins, and frequent misidentification by traditional laboratory methods. Continued genomic surveillance, improved diagnostics and new antifungal strategies are urgently needed, supported by enhanced infection prevention and control procedures.

Antifungal Agents↗

PubMed2025

Global guideline for the diagnosis and management of candidiasis: an initiative of the ECMM in cooperation with ISHAM and ASM.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

Humans↗

PubMed2026

Understanding Candidozyma (Candida) auris: genomic evolution, antifungal resistance and the growing challenges in global infection control.

Candida auris (recently renamed Candidozyma auris) is an emerging multidrug-resistant fungal pathogen, first identified in Japan in 2009. C. auris exhibits remarkable persistence on human skin and inanimate surfaces, resistance to multiple antifungals, notably fluconazole, and biofilm formation, which hinders infection control and leads to hospital outbreaks with high mortality rates. Despite ongoing research, key aspects of its reservoir origin, transmission routes and the best way to combat its spread and multidrug resistance remain unclear. Improving genomic surveillance and antifungal strategies is crucial to contain its spread and mitigate the growing public health threat posed by this resilient and potentially fatal fungal pathogen.

Humans↗

PubMed2025

Pulcherriminic acid biosynthesis and transport: insights from a heterologous system in Saccharomyces cerevisiae.

Pulcherriminic acid is an iron chelator produced by some Kluyveromyces and Metschnikowia yeasts. Its biosynthesis is encoded by the four-gene PUL cluster, where PUL1 and PUL2 are the biosynthetic enzymes, PUL3 mediates the uptake of iron-bound pulcherrimin, and PUL4 is a putative regulator. Pulcherriminic acid holds antifungal potential, as the growth of organisms unable to uptake pulcherrimin is inhibited by deficit of essential iron. Thus, a heterologous production system to further characterize and optimize its biosynthesis would be valuable. Using our in-house yeast collection and genomes available in databases, we cloned PUL1 and PUL2 genes from Kluyveromyces lactis and one of our wild Metschnikowia isolates and built an effective production system in Saccharomyces cerevisiae able to inhibit pathogenic growth. In this context, the K. lactis genes yielded faster pulcherriminic acid production than those from the Metschnikowia isolate and a combinatorial approach showed PUL1 to be the production bottleneck. We further showed that Pul3 is an importer of pulcherrimin, but also mediates the export of pulcherriminic acid and that the growth of pathogens such as Candidozyma auris and organisms encoding PUL3 in their genome, previously called "cheaters," is inhibited by pulcherriminic acid, highlighting its potential as an antimicrobial agent.

Saccharomyces cerevisiae↗