Search Results (47)

Candidozyma auris (formerly known as Candida auris) has emerged as a formidable clinical fungal pathogen as a result of its multidrug resistance and persistent colonization capabilities. In this study, three clinical C. auris strains (namely C. auris strain 01, C. auris strain 03, and C. auris strain 13) with distinct origins were characterized to investigate their phenotypic variations and mechanisms of azole resistance. Comprehensive profiling revealed significant inter-strain differences in biofilm formation, cell surface hydrophobicity, adhesion capacity, and phospholipase activity. Testing for antifungal susceptibility showed that the three clinical strains exhibited different minimum inhibitory concentrations for multiple azoles (fluconazole, voriconazole, and itraconazole) and echinocandins (anidulafungin and micafungin). Sequencing identified Y132F mutations in the ERG11 gene of the three clinical strains. Mechanistic investigations demonstrated that fluconazole exposure significantly upregulated the expression of efflux pump genes (CDR1 and CDR2) and the genes encoding their transcriptional regulators (MDR1 and TAC1b). In a murine skin colonization model, comparing data from the standard strain C. auris strain CBS12766 and clinical strains of C. auris strain 03 and C. auris strain 13 exhibited a significantly higher fungal burden of tissue, whereas strain C. auris strain 01 showed an intermediate level. Host immunity response analysis revealed that expression of the IL-1β gene was significantly elevated in C. auris strain CBS12766-infected mice, while expression of IL-6 and CXCL-1 genes was predominantly increased in the C. auris strain 01, with TNF-α gene expression levels being comparable across all strains. Histopathological examination confirmed local infiltration of inflammatory cells and mild epidermal edema, indicating active host immune engagement. Overall, our findings highlighted substantial phenotypic heterogeneity, different colonization capacities, and differences in expression of inflammatory cytokines among the C. auris strains. Further investigations into fluconazole-response mechanisms identified enhanced efflux pump activity, along with ERG11 gene Y132F mutations and transcription factor modulation among these clinical strains. Full article

Invasive candidiasis caused by drug-resistant Candida species represents a critical global health challenge, with few novel therapeutic scaffolds under development. Here, silver nanoparticles were synthesized using a 21-day fermented Chun Mee kombucha tea extract (K-AgNPs) and characterized by UV-Vis spectroscopy, transmission electron microscopy, nanoparticle tracking analysis, and Fourier-transform infrared spectroscopy. LC-MS/MS profiling of the kombucha substrate documented a phytochemical landscape dominated by epigallocatechin (up to 122,631 µg/mL) and epigallocatechin gallate (up to 415 µg/mL), with a progressive ~80% decline in epicatechin and concomitant increases in gallic acid and chlorogenic acid across the 21-day fermentation. K-AgNPs obtained were spherical, 19.4 nm (±7.9 nm SD) in diameter, with a surface plasmon resonance peak at 415 nm. FTIR confirmed phenolic, carboxylate, and glycosidic surface capping. Antifungal susceptibility testing against eight Candida species, including the WHO critical–priority pathogen Candidozyma auris, showed concordant minimum inhibitory and minimum fungicidal concentrations of 0.80–1.60 µg/mL, confirming fungicidal activity. In vivo evaluation in Galleria mellonella larvae across six infection models demonstrated that K-AgNP treatment at the species-specific MIC significantly improved larval survival versus untreated infected controls (p < 0.01–0.001), while nanoparticle-only groups maintained ≥98% survival, indicating negligible toxicity. Co-treatment amplified total hemocyte mobilization, and K-AgNP-only larvae maintained hemocyte viability above 96% at all time points, indistinguishable from negative controls. Together, these findings demonstrate antifungal activity of K-AgNPs across the genus Candida in standardized in vitro and in vivo settings and provide justification for further investigation, including head-to-head comparison against licensed antifungals and physicochemical validation of nanoparticle stability under assay conditions. Full article

Background: Fungal ocular infections, including keratitis and endophthalmitis, remain difficult to treat due to limited antifungal efficacy, poor tissue penetration, and biofilm-mediated resistance. This study evaluated the antifungal and host-protective potential of N-(4-methoxycinnamoyl)-anthranilic acid (NMCA) against Candida albicans and the multidrug-resistant Candidozyma auris. Methods: The antifungal activity of NMCA was assessed by analyzing fungal viability over time, ergosterol levels, and its interaction with fluconazole. Its antibiofilm activity was evaluated through biomass and metabolic activity measurements, together with the expression of genes involved in adhesion (ALS3, ALS5, HWP1) and membrane homeostasis (ERG11, OLE1). In addition, infected epithelial models were used to investigate epithelial damage, intracellular fungal burden, oxidative stress, and wound closure. Results: NMCA showed promising antifungal activity (MIC80 75 μg mL⁻¹ against C. albicans and 100 µg mL⁻¹ against C. auris), inducing a time-dependent reduction in fungal viability of about 4-log10 after 24 h. The compound also reduced ergosterol levels and showed synergistic interaction with fluconazole, as indicated by FICI values of 0.203 for C. albicans and 0.375 for C. auris. Moreover, NMCA markedly inhibited biofilm formation by reducing both biomass and metabolic activity up to approximately 80%, while modulating the expression of key adhesion- and membrane-related genes. Beyond its direct antifungal effects, NMCA reduced epithelial damage and intracellular fungal burden, attenuated oxidative stress, and significantly improved wound closure (reaching 76.26% and 90.46% closure in C. albicans- and C. auris-infected cells, respectively) in infected epithelial models. Conclusions: Although limited by the use of in vitro systems, these findings highlight the multifunctional profile of NMCA, which combines antifungal, antibiofilm, and tissue-protective activities. By simultaneously targeting pathogen viability, biofilm formation, and host cell integrity, NMCA appears to be a promising adjunctive candidate for the treatment of ocular fungal infections, where both pathogen eradication and tissue preservation are crucial for clinical outcomes. Full article

Background/Objectives: The increasing burden of multidrug-resistant (MDR) microorganisms and limited resources in healthcare settings are making traditional strategies based on routine isolation of all carriers unsustainable. Methods: A clinical narrative review was conducted by searching PubMed, Web of Science, and Google Scholar for studies published between 2011 and 2025. International guidelines were analyzed to synthesize a sustainable infection control strategy. Results: High-quality evidence, including cluster-randomized trials, indicates that routine contact isolation for endemic ESBL-producing Enterobacterales (IRR: 0.99) and VRE (RR: 0.93) provides no additional benefit over standard precautions. In contrast, strict isolation remains vital for high-threat pathogens such as Carbapenem-Resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), and Candidozyma auris due to their high environmental resilience and limited treatment options. Prioritization should be guided by pathogen biology, patient-specific transmission traits (e.g., diarrhea), and facility infrastructure. Conclusions: Traditional one-size-fits-all infection control is increasingly unsustainable under resource constraints. A risk-based approach prioritizing horizontal measures for low-risk pathogens enables a more balanced allocation of limited resources toward high-threat containment. Full article

Candidozyma auris (C. auris) is an emerging healthcare-associated yeast of major epidemiological concern because of its multidrug resistance and outbreak potential. We report the recovery of a single C. auris isolate from a used face mask collected in May 2025 during a blinded dental medicine quality-control programme assessing microbial contamination in the working environment. To contextualise this finding, we analysed routine diagnostic laboratory data from 2017 to 2025. The isolate underwent whole-genome sequencing for molecular characterisation, including analysis of the ERG11 gene, and antifungal susceptibility testing by EUCAST broth microdilution. In addition, 53,802 patient-related Candida spp. isolates collected between 2017 and 2025 were reviewed retrospectively; species identification had been performed by MALDI-TOF. The environmental isolate belonged to clade III and carried the V125A/F126L substitutions in ERG11, consistent with African clade isolates and associated with intrinsically high fluconazole minimum inhibitory concentrations. No C. auris was detected in routine patient specimens during the study period, whereas Candida albicans remained the predominant species in clinical samples. These findings provide no evidence of ongoing C. auris transmission at the Medical University of Innsbruck, but highlight the need for continued vigilance and robust infection-prevention measures to limit the risk posed by isolated introductions. Full article

Polyamines, putrescine, spermidine and spermine, are essential polycationic metabolites present in all eukaryotic cells, where they regulate fundamental processes including nucleic acid stabilization, translation, and stress responses. Spermidine synthase (SPDS), a member of the aminopropyltransferase (APT) family, catalyzes the transfer of an aminopropyl group from decarboxylated S-adenosylmethionine (dc-SAM) to putrescine to form spermidine. Although genomic analyses predict the presence of SPDS homologs in multiple fungal species, polyamine biosynthesis has not been experimentally characterized in the multidrug-resistant fungal pathogen Candidozyma auris. Here, we report the biochemical and functional characterization of the C. auris spermidine synthase, CauSpe3. The CauSPE3 gene complemented a Saccharomyces cerevisiae spe3Δ mutant demonstrating conserved function in vivo. Recombinant CauSpe3 was expressed in Escherichia coli, purified and analyzed using the fluorescence-based DAB-APT assay, which uses 1,2-diacetylbenzene (DAB) for polyamine detection. CauSpe3 catalyzed efficient conversion of putrescine to spermidine in the presence of dc-SAM, with K_half values of 65.5 ± 7.11 µM for putrescine and 66.9 ± 2.09 µM for dc-SAM, and V_max values of 7.1 ± 0.57 and 7.9 ± 0.12 nmol·µg⁻¹·min⁻¹, respectively. A catalytic-site mutant and heat-inactivated enzyme showed no detectable activity, and product formation was confirmed by means of thin-layer chromatography and mass spectrometry. These findings establish CauSpe3 as a functional spermidine synthase. Full article

Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant pathogenic fungus with an increased ability to cause outbreaks in healthcare facilities, leading to poor patient outcomes. Since its initial discovery in 2009, C. auris has spread rapidly across continents and is now classified by both the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) as a critical-priority pathogen. This review summarizes current knowledge on the origin, taxonomy, microbiology, and virulence mechanisms of C. auris, emphasizing its thermotolerance, osmotolerance, and biofilm-forming capacity on biotic and abiotic surfaces, as well as aspects related to its antifungal drug resistance and management. These features, together with its genomic plasticity, contribute to persistence, transmission, and drug resistance. Emerging evidence also supports a potential link between climate change and C. auris evolution, highlighting environmental adaptation as a driver of pathogenicity. Combating C. auris will require multidisciplinary efforts to mitigate its expanding global impact. Full article

Candidozyma auris (formerly Candida auris) is frequently multidrug-resistant, resulting in limited treatment options and high mortality. Comparable mortality between C. auris candidemia and non-C. auris candidemia in recent studies requires confirmation in the Middle East after adjustment for confounders. This study aimed to compare mortality rates between patients with candidemia by C. auris and non-C. auris Candida species. We retrospectively analyzed 94 cases with candidemia between January 2019 and October 2025, including C. auris candidemia (n = 30) and non-C. auris candidemia (n = 64). Inverse probability weighting was used to balance baseline confounders between groups. The primary analysis used a weighted Cox proportional hazards model. Patients in the C. auris group had more comorbidities, greater healthcare exposure, and longer hospital stays. Crude 30-day all-cause cumulative mortality was comparable between the C. auris and non-C. auris groups (log-rank test, p = 0.8). The 30-day mortality of C. auris candidemia was similar to that of non-C. auris candidemia (adjusted HR 0.40; 95% CI 0.16–1.04; p = 0.060). Large multicenter studies involving diverse populations across different regions are warranted to validate these findings. Full article

Candidemia and invasive candidiasis remain significant causes of late-onset sepsis and mortality in very-low-birth-weight infants, especially in low- and middle-income countries. This narrative review synthesizes studies published between 2008 and 2025 in Latin America, addressing epidemiology, species distribution, antifungal susceptibility patterns, risk factors, therapeutic approaches, and clinical outcomes, with international comparisons. Accordingly, we present a qualitative narrative synthesis (see Methods) rather than a formal year-over-year temporal trend quantification. Globally, five species predominate, namely Candida albicans, C. parapsilosis sensu lato (s.I.), Candida tropicalis, Nakaseomyces glabratus, and Pichia kudriavzevii, with a sustained increase in non-albicans species and growing resistance to fluconazole. In Latin America, the burden varies depending on the hospital setting; C. parapsilosis sensu lato (s.I.) predominates in NICUs, and Candidozyma auris has emerged, associated with nosocomial outbreaks and multidrug resistance. Factors such as extreme prematurity, prolonged catheter use, parenteral nutrition, and antibiotics are consistently associated with the risk of infection. Mortality remains high, influenced by diagnostic delays and species characteristics. Standardized microbiological surveillance, accurate identification, and strategies tailored to each clinical setting are required to improve outcomes in this vulnerable population. Full article

Yeast infections are a major concern in clinical settings, and several known species are recognized for their antifungal drug resistance, especially the multidrug-resistant pathogen Candidozyma auris. It is of increasing importance to identify pathogenic yeasts to improve treatment outcomes. We present a technique to identify these yeast pathogens using machine learning with a neural network (DenseNet-201) on images obtained from laser light scattering and conventional microscopy. We performed the binary classification of seven species of pathogenic yeast based on their light scattering patterns and their microscopy images. We achieved an average classification accuracy of 95.3% for light scattering patterns and 96.6% for microscopy images of the yeast cells. We also demonstrate high classification accuracy when isolating Candidozyma auris images from all other species combined, at an average of 95.1% for light scattering patterns and 96.7% for microscopy images. The high average classification accuracies suggest that both light scattering and microscopy image data can be combined with machine learning models to classify pathogenic yeasts. Full article

Candidozyma auris is an emerging opportunistic fungal pathogen that can cause serious catheter-related blood stream infections associated with high morbidity and mortality. The traditional antifungal treatment with polyenes, azoles or echinocandins is becoming less effective due to both intrinsic and developed resistance, complicating treatment. This study demonstrates the potent fungicidal activity of carboxyl-functionalized graphene quantum dots (cGQDs) against a panel of C. auris strains, spanning clades I to V, and a Candida albicans reference strain. Photoactivation of cGQDs in suspension with 435 nm blue light killed 99.9% of the fungi within 30 min even though the majority of test strains were resistant to at least one conventional antifungal. Moreover, cGQDs coated on flexible polydimethylsiloxane surfaces and commercial catheters via electrostatic layer-by-layer deposition with alternating positively charged polydiallyldimethylammonium polymer showed strong fungicidal activity against C. auris and C. albicans. These findings show that the cGQDs, both in suspension and in a thin film coating, have potential for future clinical development. In particular, their application to catheters may help prevent Candidozyma and Candida catheter-related infections. Full article

The rising prevalence of Candidozyma auris and Candida parapsilosis, characterized by high surface persistence and biofilm-forming capabilities, challenges the efficacy of standard laundry and surface disinfection protocols. This study evaluated the effectiveness of laundry processes according to EN 17658 at 20 °C, 30 °C and 40 °C and two surface disinfectants (bead assay for biofilms) against two Candida albicans strains, C. parapsilosis, and C. auris. Results indicated that C. auris is more resilient than other strains, surviving laundry treatment with activated oxygen bleach at 40 °C; maximum efficacy required a colour powder detergent supplemented with a bleach-releasing additive at 40 °C. While alcohol- and aldehyde-based surface disinfectants were effective per EN 13697 criteria, their efficacy against biofilms—tested on glass, stainless steel, polypropylene, and PTFE—was highly dependent on both the strain and the surface material. These findings demonstrate the reduced susceptibility of C. auris to standard laundry disinfection and highlight that biofilm eradication is a complex process influenced by strain-specific attributes and surface characteristics. Full article

Invasive fungal diseases (IFDs) represent an escalating global health threat, compounded by the rapid emergence of antifungal resistance (AFR). This review synthesizes the contemporary landscape of AFR from clinical and microbiological perspectives, providing actionable insights for clinical practitioners. We examine the epidemiology of critical pathogens, including Candidozyma auris, clonal Candida parapsilosis, azole-resistant Aspergillus fumigatus, and dissect the underlying molecular mechanisms, from genetic mutations in ERG11 and cyp51A to novel emerging epigenetic and adaptive strategies. We critically appraise the diagnostic gap between phenotypic testing and clinical urgency, highlighting the role of rapid molecular assays and next-generation sequencing. Finally, we evaluate evidence-based therapeutic strategies, including the integration of novel agents such as rezafungin, ibrexafungerp, olorofim, and fosmanogepix), while emphasizing the imperative of antifungal stewardship, infection prevention and control in mitigating resistance, and “One-Health” interventions. Full article

Candida auris is a critical emerging pathogen of high priority due to its ability to develop multidrug resistance to various antifungals. Given the increase in cases associated with C. auris, it is essential to evaluate new candidates with antifungal potential. In this context, flavonoids represent a promising source for the development of new therapeutic alternatives. In this study eleven flavonoids were evaluated for their antifungal activity against C. auris strains from clades III and IV. The flavonoids showed dose-dependent inhibition of C. auris growth. Toxicity tests were conducted using the in vivo Tenebrio molitor model. The flavonoids exhibited toxicity levels either comparable to or lower than reference antifungals. Also, the study examined the ability of the flavonoids to inhibit efflux pumps. Some of the flavonoids (quercetin, fisetin, hesperetin, luteolin and apigenin) reduced efflux pump activity, which is an important feature since these pumps actively expel antifungal drugs from the cell, reducing the drug’s effectiveness. This suggests that the flavonoids might inhibit efflux pump activity, potentially enhancing the efficacy of antifungal treatments. The study supports the potential of flavonoids as new therapeutic agents for C. auris. Since they target efflux pumps, which are a significant mechanism of resistance in C. auris, flavonoids could be used either alone or in combination with existing antifungals to improve treatment outcomes. Full article

Candidozyma (Candida) auris is a fungal pathogen associated with life-threatening invasive infections and high mortality rates. It is becoming a major global public health concern due to its ability to resist multiple antifungal drugs and spread in healthcare settings. Despite this, little is known about the mechanisms underlying drug resistance, fungal development, pathogenesis, and virulence. Among the factors contributing to these processes, transporters play a central role in fungal biology, regulating nutrient acquisition, metabolite exchange, ion homeostasis, and drug efflux. However, the composition and diversity of transporter systems in C. auris remain poorly defined. Through genomic analysis, we identified 686 transporters and 125 accessory factors involved in transport in C. auris, most of which had not been characterized. These transporters and accessory factors were classified into seven classes, 22 subclasses, and 215 families, reflecting substantial functional diversity. Comparative analyses with other pathogenic Candida species and Saccharomyces cerevisiae reveal lineage-specific divergence in several transporter families. We also integrated multiple publicly available RNA-seq datasets encompassing antifungal drug exposure and drug-resistant isolates and identified subsets of transporters that are transcriptionally responsive in distinct antifungal conditions, including members of families implicated in drug transport, metabolism, and ion homeostasis. Together, this study defines the landscape of transporter systems in C. auris and highlights transporter families that may contribute to stress adaptation and antifungal responses, providing a resource for future functional and mechanistic investigations. Full article