Search Results (481)

Trichosporon is a type of non-candida yeast-like fungus. At one time, it was commonly reported in immunocompromised patients, but after the introduction of fluconazole as prophylaxis and for the treatment of fungal infections, there was a decrease in the incidence of the disease. With the introduction of echinocandins as the first line of treatment for fungal infections, and the intrinsic resistance of Trichosporon to the drug, there has been a small but increased reported incidence of the disease. Trichosporon usually causes skin infections, but invasive disease can occur in vulnerable patients. Endocarditis due to Trichosporon has been reported rarely, and usually occurs in prosthetic valves. In this paper, we report a patient with dialysis-dependent chronic kidney disease who presented with fever and was found to have native aortic valve endocarditis. In view of the large vegetation, he underwent early aortic valve replacement. Both the blood and tissue cultures grew Trichosporon spp. Post-operatively, he developed fungal septic shock, deteriorated, and died. Invasive Trichosporon disease has been associated with high rates of mortality ranging from 30 to 90%. There is limited literature on endocarditis resulting from Trichosporon. Specific treatment recommendations are unavailable, and a combination of surgery and prolonged antifungal medication will generally be required. Full article

Intestinal fungal overgrowth (IFO) is an increasingly recognized yet underexplored component of gut dysbiosis with potential implications for gastrointestinal and systemic disease. While bacterial microbiota have historically garnered research attention, recent advances in sequencing technologies have highlighted the importance of the gut mycobiome in maintaining intestinal homeostasis. Disruption of fungal–bacterial balance, particularly involving Candida albicans, C. tropicalis, and C. glabrata, may contribute to symptom generation through immune activation, epithelial barrier dysfunction, biofilm formation, and the production of toxic metabolites such as acetaldehyde and candidalysin. Emerging clinical evidence suggests that IFO is associated with persistent gastrointestinal symptoms, including bloating, abdominal discomfort, and altered bowel habits, particularly in patients who do not respond to conventional therapies targeting bacterial overgrowth. Furthermore, fungal dysbiosis involving Malassezia restricta and Saccharomyces cerevisiae has been associated with inflammatory bowel disease, metabolic disorders, and systemic immune dysregulation; however, the nature and directionality of these relationships remain incompletely understood. Despite increasing recognition, the diagnosis of IFO remains challenging due to a lack of standardized criteria and validated non-invasive tools. Therapeutic strategies, including antifungal agents such as fluconazole and nystatin, as well as microbiome-targeted interventions, show promise but require further validation. This review provides a comprehensive synthesis of current evidence regarding the epidemiology, pathophysiology, clinical manifestations, diagnostic challenges, and therapeutic implications of IFO, with particular emphasis on species-specific mechanisms. Recognition of the intestinal mycobiome as a potentially important component of gut health may provide new perspectives for understanding gastrointestinal disorders and inform future precision medicine approaches. Full article

The dimorphic fungus Talaromyces marneffei causes talaromycosis, a life-threatening fungal disease with limited treatment options. Olorofim, a first-in-class orotomide antifungal that targets pyrimidine synthesis essential for fungal growth, has low minimum inhibitory concentration (MIC) against T. marneffei and clinical efficacy against other invasive fungal diseases. Here, we tested the hypothesis that olorofim synergistically enhances amphotericin B (AmB), a potent membrane-targeting antifungal, against T. marneffei in 55 clinical isolates using a validated colorimetric checkerboard assay. The MIC was defined as the lowest drug concentration inhibiting ≥ 95% of fungal growth. Drug interactions were assessed using the fractional inhibitory concentration index (FICI), which defines ≤0.5 as synergy, 0.5 < FICI ≤ 4.0 as indifference, and FICI > 4 as antagonism. We found that interactions between AmB and olorofim were indifferent across all 55 isolates (0.5 < FICI ≤ 1.03). Time-kill assays showed an expected concentration-dependent fungicidal activity for AmB, but a concentration-independent fungistatic activity for olorofim against T. marneffei. Combinations of AmB and olorofim were also indifferent in time-kill experiments. Although synergy was not observed, and olorofim is unlikely to enhance AmB induction therapy, olorofim may have a role in the consolidation and maintenance therapy of talaromycosis. Full article

The global rise in multidrug-resistant (MDR) fungal pathogens has positioned Candida auris and Candida glabrata as major threats to public health. In recent years, these pathogens have increasingly been reported beyond traditional hospital settings, including neonatal intensive care units, long-term care facilities, oncology wards, and post-pandemic critical care environments. International surveillance bodies, including the Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO), and regional monitoring networks, have documented escalating antifungal resistance, complex outbreak dynamics, and persistent gaps in infection control implementation. C. auris has emerged as a major etiological agent of healthcare-associated outbreaks, particularly in intensive care and neonatal units. Surveillance data indicate that a high proportion of C. auris isolates exhibit resistance to azoles, often exceeding 80% in some regions, while echinocandin resistance remains variable. Resistance patterns have evolved from predominantly azole resistance to broader multidrug-resistant phenotypes, including treatment-emergent echinocandin resistance. Six genetically distinct clades (I–VI) have been identified, with Clades I, III, and IV associated with large-scale outbreaks, whereas available data suggests that Clades II, V, and VI are more geographically restricted, although evidence for the recently described clades remains limited. C. glabrata is increasingly recognized as a major cause of invasive candidiasis, with rising resistance reported across multiple regions. While reduced azole susceptibility was historically predominant, emerging evidence highlights rising dual azole–echinocandin resistance, adaptive microevolution during antifungal therapy, and biofilm-associated tolerance mechanisms. Despite these advances, significant gaps persist in global resistance surveillance and in the mechanistic understanding of virulence and antifungal adaptation. Current mitigation strategies include antifungal stewardship programs, expanded resistance testing, and strengthened surveillance systems. Advances in rapid diagnostic technologies such as matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry, polymerase chain reaction (PCR)-based assays, and genomic surveillance have improved pathogen identification and outbreak detection, although accessibility remains limited in resource-constrained settings. This review examines emerging epidemiological, genomic, and antifungal resistance trends in C. auris and C. glabrata and highlights key priorities for improving diagnosis, surveillance, stewardship, and management of multidrug-resistant Candida infections. Full article

Fungal β-1,3-glucans are structurally conserved polysaccharide components of the fungal cell wall that exhibit potent immunomodulatory activity. These molecules are recognized by pattern recognition receptors, Toll-like receptors, complement receptor 3, lactosylceramide, scavenger receptors, and EphA2. Binding of β-1,3-glucans through these receptors triggers coordinated innate and adaptive immune responses such as cytokine production, phagocytosis, and trained immunity. In addition to receptor-mediated immune activation, dietary β-1,3-glucans function as fermentable prebiotic fibers that modulate gut microbiota composition, increase short-chain fatty acid production, and strengthen epithelial barrier integrity. These combined immunological and microbiome-mediated effects position β-1,3-glucans as key regulators of gut homeostasis. Preclinical and emerging clinical evidence supports broad therapeutic potential across multiple disease domains, including inflammatory bowel disease, metabolic disorders, respiratory infections, and cancer. In oncology, β-1,3-glucans enhance anti-tumor immunity, improve responses to monoclonal antibodies and chemotherapy, and serve as promising adjuvants in vaccine-based strategies. Additionally, β-1,3-glucan is widely used as a biomarker for invasive fungal infections and represents a validated target of antifungal therapies such as echinocandins. Despite these advances, clinical translation remains limited by heterogeneity in glucan source, structure, and formulation, as well as a lack of appropriately powered, standardized human clinical trials. Future efforts should focus on clarifying mechanisms of action, as well as rigorous clinical evaluation, to fully define the therapeutic utility of fungal β-1,3-glucans. Full article

Phaeohyphomycosis is an opportunistic fungal infection caused by dematiaceous fungi and is considered uncommon in dogs, particularly when associated with visceral or systemic involvement. Pulmonary disease as a primary site of infection is rarely reported in veterinary medicine and is often associated with an unfavorable outcome. This report describes a fatal case of pulmonary phaeohyphomycosis in a dog, characterized by severe granulomatous pneumonia, vascular invasion by pigmented fungal hyphae, and the development of large vessel thrombosis. Histopathological examination revealed septate, pigmented hyphae consistent with dematiaceous fungi associated with an intense granulomatous inflammatory response. Although molecular analysis by polymerase chain reaction was unsuccessful due to the absence of amplifiable DNA in archived FFPE tissue, the clinicopathological correlation and histopathological findings were sufficient to support a diagnosis consistent with phaeohyphomycosis. Severe pulmonary inflammation likely contributed to vascular endothelial injury, resulting in pulmonary hypertension and thrombosis of major veins. This case highlights the diagnostic and clinical challenges associated with phaeohyphomycosis in dogs and emphasizes the importance of considering this infection in the differential diagnosis of chronic or progressive respiratory diseases accompanied by systemic complications. Furthermore, it reinforces the relevance of histopathology and comprehensive clinicopathological evaluation when molecular confirmation of the etiological agent is not achievable. Full article

Mucormycosis, triggered by fungi of the order Mucorales, represents a potentially fatal invasive mycosis, with death rates over 50% despite intensive therapy. The COVID-19 pandemic brought a sharp increase in cases, especially in individuals with diabetes mellitus and those undergoing immunosuppressive treatment, emphasizing significant gaps in our comprehension of disease pathogenesis. Emerging molecular studies have highlighted key virulence factors, such as the CotH family of invasins that facilitate endothelial invasion via interaction with glucose-regulated protein 78 (GRP78), complex iron acquisition systems necessary for fungal growth, and the release of mucoricin, a ricin-like toxin that impairs vascular integrity. Host defense depends mainly on innate immunity, with neutrophils and macrophages working as critical effector cells, while adaptive Th1 and Th17 responses aid in the fungal removal. Mucorales use a variety of immune evasion techniques, such as pathogen-associated molecular pattern (PAMP) masking via cell wall transformations, resistance to phagocytic death, and metabolic utilization of host factors including hyperglycemia and increased free iron in diabetic ketoacidosis (DKA). This review summarizes current evidence of the molecular processes underlying mucormycosis pathogenesis, underscoring host–pathogen interactions at the cellular and molecular levels, immune evasion tactics, and translational potential for new diagnostic and therapeutic approaches. Comprehending these molecular processes is crucial for creating efficient therapies against mucormycosis in an era of growing immunocompromised patients and expanding infectious disease synergies. Full article

Although Aspergillus fumigatus has been identified as a critical fungal pathogen by the World Health Organization, diagnosis of the various types of aspergilloses remains unsatisfactory. New biomarkers of disease and accessible test systems are needed. Moreover, new treatment concepts are required to address infections caused by this invasive pathogen. Siderophore production by A. fumigatus offers opportunities for both improved diagnosis and potential therapy. Here, we report the development of a competitive ELISA that detects ferrated triacetylfusarinine C (FeTAFC) using a recombinant monoclonal IgG [anti-FeTAFC]. The FeTAFC ELISA can detect FeTAFC in human urine, a matrix proposed to be especially suitable for disease diagnosis because of the non-invasive nature of specimen collection. In addition, a novel assay was developed to assess the in vitro inhibitory properties of the IgG [anti-FeTAFC] towards A. fumigatus mutant and wild-type growth under iron-limiting conditions. The growth of A. fumigatus ΔsidD, deficient in TAFC and precursor fusarinine C (FsC) biosynthesis, was significantly reduced (p = 0.0003) in the presence of the antibody. While the growth of A. fumigatus wild-type was less affected in the presence of the antibody, the ratio of secreted TAFC:FsC was increased due to increased conversion of FsC to TAFC—likely because of extracellular complexation of FeTAFC by the IgG [anti-FeTAFC]. This work shows the utility of the IgG [anti-FeTAFC] for the detection of A. fumigatus and initial evidence for limiting fungal growth by attenuation of FeTAFC uptake. Full article

Mesenchymal stem/stromal cells (MSCs) are widely recognized as potent modulators of inflammation and immune function in bacterial and viral infections. However, their roles in fungal disease remain comparatively under-defined despite the growing clinical burden of invasive and opportunistic mycoses. This Feature Review synthesizes emerging evidence that MSCs influence antifungal outcomes through two complementary axes: (i) host-directed effects, including modulation of immune responses, particularly macrophage responses, and tissue/barrier conditioning; and (ii) fungus-directed effects (direct antifungal activity mediated by contact-dependent mechanisms and secreted antimicrobial factors). We will summarize how MSCs reshape cytokine and chemokine networks and tune innate immune effector functions, with emphasis on macrophage polarization, pattern-recognition receptor signaling, and downstream phagocytic and fungicidal pathways. In parallel, we will review data suggesting that MSCs can interact more directly with fungal pathogens through sensing, physical engagement, and secretion of antimicrobial mediators while highlighting mechanistic uncertainties and model-dependent limitations. A dedicated section will address MSC-derived secretome products (conditioned media, extracellular vesicles) as a cell-free strategy to enhance antifungal immunity. We will critically evaluate conflicting findings across studies, highlighting that outcomes depend on pathogen and host context. Clarifying these context dependencies is essential to rationally develop MSC or secretome-based interventions that are safe, reproducible, and tailored to specific fungal pathogens and patient populations. Full article

The invasive fungal pathogen Pseudogymnoascus destructans is responsible for the collapse of several North American bat species through an infectious fungal skin disease known as White-Nose Syndrome (WNS). Recent transcriptomic studies have suggested that trace copper ion acquisition is essential for P. destructans propagation on its animal hosts. However, little is known about the mechanistic details of P. destructans adaptation occurring at the protein level. In this study, we report the global proteomic adaptation of P. destructans under chronic Cu-stress growth conditions employing chemically defined media. We identify 4340 P. destructans proteins, or approximately 47.8% of the predicted proteome, spanning a dynamic intensity range of six orders of magnitude. Chronic Cu-withholding stress leads to substantial alterations in the proteome, with 1398 differentially abundant proteins (DAPs) exhibiting statistically significant (p < 0.05) changes in protein levels compared to control growth conditions. We find that Cu-withholding stress induces increased levels of proteins associated with high-affinity Cu-acquisition, changes in intracellular superoxide dismutase (SOD) levels, and alterations in mitochondrial proteins related to aerobic respiration. In contrast, chronic Cu-overload stress leads to 390 DAPs (p < 0.05), which are more widely distributed across the proteome, with several DAPs associated with genomic stability and basic metabolism. Additionally, in this report, we present assessment of antisera products against intracellular and cell-surface protein targets of P. destructans that are effective for indicating Cu-withholding stress by western blotting. Together this report, provides insight into P. destructans adaptability to copper stress and identifies fungal proteins that may alleviate copper stress in the WNS infection niche. Full article

A history of invasive mold disease (IMD) often delays or contraindicates allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. Given the limited data on pediatric patients with pre-allo-HSCT IMD, we aimed to describe the management and clinical outcomes of a cohort of children with IMD prior to allo-HSCT through day +100 post-transplantation. Between 2021 and 2024, ten pediatric patients were identified with proven or probable IMD. Their median age was 8.5 years. The most common pathogens were Aspergillus (n = 5) and Fusarium (n = 4). Infections most frequently involved the lungs followed by paranasal sinuses, bloodstream, liver, and skin. All patients demonstrated clinical improvement before transplantation, and by day +100 post-HSCT, no IMD relapses or infection-related mortality were observed. These findings suggest that complete radiologic or clinical resolution is not a prerequisite for proceeding with transplantation. Recent IMD should not be considered an absolute contraindication to urgent allo-HSCT when clinical improvement is evident, as transplantation facilitates immune reconstitution necessary for definitive infection control. Full article

Aspergillus fumigatus is a leading cause of invasive fungal disease in humans and is classified as a critical priority threat by the World Health Organization. Triazole antifungals remain the cornerstone of therapy, yet their effectiveness is steadily being eroded by the continuous rise in drug resistance. Most resistance mechanisms trace back to mutations in Cyp51A, spawning well-defined genotypes such as TR₃₄/L98H and TR₄₆/Y121F/T289A. However, the Cyp51A genotype–phenotype landscape in A. fumigatus is far from straightforward. Isolates that share an identical TR genotype can display strikingly divergent susceptibility profiles, and mutational hotspots in Cyp51A, such as G54, M220 and G448, are linked to varying resistances, challenging assumptions about predictable resistance behavior. Complicating matters further, an expanding array of resistance mechanisms, independent of Cyp51A, is now being uncovered. This review summarizes the current state of knowledge on azole resistance in A. fumigatus, dissecting the intricate genotype–phenotype relationships, spotlighting emerging non-Cyp51A pathways and outlining future strategies to enhance the detection and clinical management of antifungal resistance. Full article

Basil essential oil (BEO) has emerged as a promising natural alternative to antibiotic growth promoters in poultry production. BEO has shown antimicrobial, antifungal, anticoccidial, antioxidant, and insecticidal properties. BEO exhibits broad antimicrobial activity against Gram-positive and Gram-negative pathogens, and modulates gut microbiota by decreasing Escherichia coli and Staphylococcus spp. Anticoccidial effects include reduced oocyst shedding, improved intestinal morphology, and downregulation of pro-inflammatory cytokines. Antifungal activity reduces fungal load and inhibits Aspergillus spp., with implications for control spoilage and aflatoxin risk. BEO at a concentration of 40 ppm was effective in preventing E. tenella invasion, showing an average reduction in invasion by 36% in primary chicken epithelial cells. Antioxidant benefits include enhanced intestinal and systemic antioxidant status. Advanced nanoformulation technologies, particularly nano-encapsulation, have substantially overcome several limitations for BEO application in poultry. Further research is still required to assess the efficacy of nano-encapsulated BEO for enhancing overall poultry industry productivity. This review synthesizes current evidence on BEO integration in the poultry production sections, from nutrition and disease control to product preservation and farm hygiene, and evaluates technological solutions that address formulation barriers. Moreover, it discusses critical research gaps and proposes future directions for enhancing BEO applications in sustainable poultry production systems. Full article

Fusarium ear rot (FER), caused by F. verticillioides, is a devastating disease in maize, leading to substantial yield losses and mycotoxin contamination. Therefore, revealing the molecular mechanisms underlying FER resistance is essential for crop breeding. Here, we performed integrated transcriptomic and metabolomic analyses on two maize inbred lines with contrasting FER resistance: the resistant line ZL30-12 (ZL30) and the susceptible line 92C0468U (92C). Following F. verticillioides inoculation, ZL30 exhibited sustained inhibition of fungal colonization and fumonisin accumulation, whereas 92C showed progressive disease development and elevated fumonisin levels. Both transcriptomic and metabolomic analyses converged on the phenylpropanoid pathway, with DEGs enriched in phenylpropanoid metabolism and DAMs enriched in phenylpropanoid biosynthesis, highlighting its central role in resistance. Further integrative analysis revealed that the lignin biosynthetic process, a key branch of phenylpropanoid metabolism, plays an important role in resistance. Several key DEGs (ZmPAL, ZmHCT, peroxidases, and ZmCOMT) and DAMs (sinapic acid, sinapaldehyde, coniferin, cinnamic acid, and caffeic acid) were differentially regulated between the two lines. Correlation analysis revealed a significant correlation between ZmCOMT expression and sinapic acid accumulation. RT-qPCR validation confirmed the expression patterns of key lignin-associated genes. The elevated activation of lignin biosynthesis in ZL30, via time-dependent induction of key genes (ZmPAL, ZmHCT, and peroxidases), suggests an increase in lignin accumulation, which likely reinforces cell wall integrity and restricts fungal invasion, thereby contributing to FER resistance. Collectively, these findings provide insights into the molecular mechanisms of FER resistance and identify key lignin-associated genes as promising targets for maize breeding. Full article

Filamentous fungal infections of breast implants remain underrecognized compared with infections caused by Candida species and bacteria, despite their potential to induce significant inflammatory pathology. This commentary highlights the distinctive ability of filamentous fungal biofilms to penetrate deeply into the implant capsule, a feature that may contribute to distinct pathogenic behaviour compared with bacterial or yeast biofilms. We discuss how this invasive behavior may contribute to the perception that reported cases represent the first documented breast implant-associated fungal infections, when in fact such infections may be under-recognised and under-investigated. By drawing attention to these mechanisms and their clinical implications, this commentary aims to stimulate greater awareness and further investigation within the fields of infectious diseases and pathogen research. Full article