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PubMed2024

Vertebrate and invertebrate animal infection models of Candida auris pathogenicity.

Candida auris is an emerging fungal pathogen with several concerning qualities. First recognized in 2009, it has arisen in multiple geographically distinct genomic clades nearly simultaneously. C. auris strains are typically multidrug resistant and colonize the skin much better than most other pathogenic fungi; it also persists on abiotic surfaces, enabling outbreaks due to transmission in health care facilities. All these suggest a biology substantially different from the 'model' fungal pathogen, Candida albicans and support intensive investigation of C. auris biology directly. To uncover novel virulence mechanisms in this species requires the development of appropriate animal infection models. Various studies using mice, the definitive model, are inconsistent due to differences in mouse and fungal strains, immunosuppressive regimes, doses, and outcome metrics. At the same time, developing models of skin colonization present a route to new insights into an aspect of fungal pathogenesis that has not been well studied in other species. We also discuss the growing use of nonmammalian model systems, including both vertebrates and invertebrates, such as zebrafish, C. elegans, Drosophila, and Galleria mellonella, that have been productively employed in virulence studies with other fungal species. This review will discuss progress in developing appropriate animal models, outline current challenges, and highlight opportunities in demystifying this curious species.

Animals↗

PubMed2026

Antimicrobial photodynamic therapy mediated by phenothiazine photosensitizers against Candida albicans and Candida auris: a systematic review.

Fungal infections caused by Candida albicans and Candida auris represent an increasing clinical challenge, particularly due to biofilm formation and rising antifungal resistance. Antimicrobial photodynamic therapy (aPDT) has emerged as a potential alternative strategy, with phenothiazine-based photosensitizers being among the most extensively investigated compounds. This systematic review aimed to evaluate the application of phenothiazine-mediated aPDT in in vitro studies against C. albicans and C. auris. A comprehensive search was conducted in PubMed, Embase, and Scopus, including studies published within the last 10 years. Forty in vitro studies met the eligibility criteria and were synthesized descriptively due to substantial methodological heterogeneity. Overall, aPDT was associated with reductions in fungal viability, with generally greater effects reported in planktonic models compared with biofilms. Methylene blue was the most frequently investigated photosensitizer, applied across a broad range of concentrations and dosimetric parameters, resulting in variable antifungal responses. Other phenothiazine derivatives, including toluidine blue O, dimethyl methylene blue, new methylene blue, and S137, were also associated with antifungal activity under specific experimental conditions but remain comparatively underexplored. Studies involving C. auris were less frequent and suggested lower susceptibility compared with C. albicans, particularly in biofilm models. Given the substantial variability in experimental protocols, especially regarding photosensitizer concentration, light parameters, and biofilm maturation, the findings should be interpreted with caution and limit direct comparison across studies. These findings support the antifungal potential of phenothiazine-mediated aPDT while emphasizing the need for methodological standardization and expanded investigation of C. auris.

Photochemotherapy↗

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

Multi-Omics Analysis of Experimentally Evolved Candida auris Isolates Reveals Modulation of Sterols, Sphingolipids, and Oxidative Stress in Acquired Amphotericin B Resistance.

Clinical isolates of Candida auris show a high prevalence of resistance to Amphotericin B (AmB)-an uncommon trait in most Candida species. Alterations in ergosterol biosynthesis can contribute to acquired AmB resistance in C. auris laboratory strains but are rarely seen in clinical isolates. In this study, we experimentally evolved two drug-susceptible Clade II isolates of C. auris to develop AmB resistance. The evolved strains displayed a four to eight fold increase in MIC50 compared to the parental cells. We analyzed changes in their karyotype, genome, lipidome, and transcriptome associated with this acquired resistance. In one lineage, AOX2 was upregulated, and its deletion reversed the AmB resistance phenotype. The aox2Δ mutant also failed to evolve AmB resistance under experimental conditions. In the same lineage, restoring the UPC2 S332R and RTG3 S101T mutations to the wild-type allele restored AmB susceptibility. In another lineage, the ergosterol and sphingolipid pathways were observed to play a critical role, and upregulation of the ERG genes elevated the total sterol content, while significant downregulation of HSX11 (glucosylceramide synthase) resulted in lower levels of glucosylceramides. To our knowledge, this study is the first to show that AmB resistance in C. auris can be acquired through mechanisms both dependent on or independent of sterol content modulation, highlighting Aox2 and Upc2 as key regulators of amphotericin resistance.

Amphotericin B↗

PubMed2025

Candida auris outbreak in a cardiothoracic transplant intensive care unit: implications for infection prevention practices and keeping pace with an evolving landscape.

OBJECTIVE: To describe the mitigation strategies for a Candida auris outbreak in a cardiothoracic transplant intensive care unit (CTICU) and its implications for infection prevention practices. DESIGN: Retrospective cohort study from July 2023 to February 2024. SETTING: A large academic medical center. METHODS: A multidisciplinary team convened to conduct the outbreak investigation and develop mitigation strategies in the CTICU. RESULTS: From July 2023 to February 2024, 34 possible hospital-onset cases of C. auris were identified in our CTICU. Whole-genome sequencing and phylogenetic analysis based on pairwise single nucleotide polymorphism (WG-SNP) distance revealed two distinct outbreak clusters. Of the 34 patients, 11 (32.3%) were solid organ transplant recipients and 12 (35.3%) had a mechanical circulatory support device. Of the cohort, only 11/34 (32.3%) had prior exposure to high-risk healthcare facilities within six months prior to admission, as follows: acute inpatient rehabilitation facilities (AIRs) (n = 5, 14.7%), skilled nursing facilities (SNFs) (n = 3, 8.8%), and long-term acute care hospitals (LTACHs) (n = 3, 8.8%). The cohort had a median of 22.0 antibiotic-days prior to their positive results. Five (14.7%) patients had C. auris candidemia, three of whom expired likely due to infection. Infection Prevention (IP) interventions addressed several modes of transmission, including healthcare personnel hands, shared patient equipment, and the environment. CONCLUSION: Our experience suggests that the epidemiology of C. auris may be changing, pointing towards a rising prevalence in acute care settings. IP interventions targeting hand hygiene behavior and promoting centralizing cleaning and disinfection of shared patient equipment may have contributed to outbreak resolution.

Humans↗

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

Large-scale discovery platform enables identification of peptides targeting drug-resistant candidiasis.

Natural products have an unparalleled track record as sources of clinical drugs. Among them, nonribosomal peptides (NRPs) stand as one of the most therapeutically significant classes, encompassing numerous approved anti-infective and anticancer agents. Yet, discovering bioactive NRPs remains profoundly challenging due to their complex biosynthesis and chemical architecture. Here, we present NPDiscover, a pathogen-oriented, scalable bioinformatics platform that integrates genome mining, metabolomics, and machine learning to identify NRPs active against drug-resistant pathogens. Applying NPDiscover to Actinobacteria datasets, we discovered edaphochelin A, a previously unreported NRP that kills multi-drug-resistant Candida auris and Candida glabrata by disrupting respiratory chain proteins. Structural elucidation via nuclear magnetic resonance and mass spectrometry, alongside in vitro and in vivo validation, confirmed its efficacy, safety, and a mode of action distinct from existing antifungals-establishing edaphochelin A as a compelling drug candidate and NPDiscover as a powerful engine for scalable natural product discovery.

CP: biotechnology↗

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

Cryo-EM structures of Candida albicans chitin synthase Chs1 reveal a druggable translocation channel.

Invasive candidiasis is a leading cause of hospital-acquired bloodstream infections with high mortality. While the fungal cell wall is an excellent therapeutic target, inhibitor development against the essential chitin synthase (Chs) has been hampered by the absence of structural and mechanistic understanding of class II Chs, which contribute to fungal viability. Here we present cryo-electron microscopy structures of Candida albicans class II Chs (CaChs1) at 2.93-3.38 Å resolution, providing insights into its mechanisms of early elongation, chito-oligomer translocation and inhibition by the CaChs1-specific non-competitive inhibitor diynyl arylamine (DA). Chitin elongation and translocation are coupled to coordinated motion of the glycosyltransferase domain and the dimer interface. Notably, DA binds within the chitin translocation channel where a regulatory lipid resides and inhibits the enzyme by occluding product polymer extrusion. Importantly, DA showed potent synergy with the class I Chs inhibitor nikkomycin Z against C. albicans and Candida auris. These findings establish the chitin translocation channel as a druggable site for rational antifungal design.

Journal Article↗