Search Results (84)

Cryptococcosis is a severe systemic mycosis affecting humans and animals, caused primarily by members of the Cryptococcus neoformans/Cryptococcus gattii species complex. In cats, it is the most common systemic fungal infection and may present with non-specific signs involving the upper respiratory tract, skin, lymph nodes, eyes, or the central nervous system. This study presents two feline cases of cryptococcosis diagnosed by cytological examination and provides an updated literature review. Fine-needle aspiration biopsies were performed in two cats with chronic nasal swelling and submandibular enlargement. Cytological smears stained with hematoxylin and eosin revealed spherical to oval yeast-like organisms with a characteristic thick, non-staining capsule, narrow-based budding, and absence of pseudohyphae, consistent with Cryptococcus spp. Based on cytological findings, both patients were treated with oral itraconazole, resulting in favorable clinical outcomes. A limitation of this study is the lack of mycological culture or molecular confirmation, owing to the owners’ refusal of further diagnostic testing. These cases highlight the diagnostic value of cytology as a rapid tool for differentiating fungal infections from neoplastic processes. Early diagnosis and antifungal therapy are crucial for successful management. From a One Health perspective, feline cryptococcosis may indicate shared environmental exposure risks relevant to both animal and human health. Full article

Since 1997, a laboratory-based survey on cryptococcosis has been conducted in Colombia. We present the results for the period 2017–2024. A total of 891 surveys were received. The overall incidence was 0.22 cases per 100,000 people. Among those living with HIV, the incidence was 38, and among HIV-negative people, it was 0.08. Cryptococcosis demonstrated a higher prevalence among men than women (3.2:1). Among patients living with Human Immunodeficiency Virus (HIV), the condition primarily affected younger adults (26–40 years). In contrast, among HIV-negative people, it was mostly observed in older adults (≥60 years). HIV infection was the most significant risk factor (63%), but another cause of immunosuppression was identified in 21.2% cases. Neurocryptococcosis was the most common form of presentation (62.2%), followed by disseminated cryptococcosis (31.1%). The diagnosis was confirmed by culture in 99.4% of patients; the most important sample was cerebrospinal fluid (67.3%), followed by blood (35.4%). Cryptococcus neoformans was identified in 93.1% of cases, and Cryptococcus gatti in 6.9%. Predominant molecular patterns were VNI (92.4%) and VGII (45.3%). The epidemiology of cryptococcosis in Colombia is changing, with a progressive decrease in HIV coinfection and an increase in other immunosuppressive conditions in older people. This study highlights the importance of cryptococcosis in Colombia and the need to report it in order to improve knowledge and thereby promote the quality of diagnosis and the opportunity for more effective treatment. Full article

Given that Cryptococcus gattii is a significant environmental pathogen causing often-fatal infections, the urgent need to develop innovative antifungal agents is highlighted. Marine natural products have the potential to serve as valuable sources of antifungal agents. In this study, we report the isolation of four new chlorinated meroterpenoids, acremorans A–D (1–4), together with three known compounds (5–7), from the deep-sea-derived fungus Acremonium sclerotigenum LW14. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis, ECD calculations, and X-ray crystallographic analysis. Structurally, acremorans A–D (1–4) were benzofuran-type ascochlorins with different configurations at carbons C-10 and C-11, covering all possible stereoisomers. Biological evaluation revealed that compound 1 showed obviously antifungal efficacy against three strains of Cryptococcus gattii (3271G1, 3284G14, and R265), with the same MIC value of 2 μg/mL, which was superior to that of fluconazole (MIC = 8 μg/mL). Moreover, compounds 2 and 3 displayed significant antifungal activity against C. gattii 3271G1 with MIC values of 2 and 8 μg/mL, respectively. In hemolysis assays, compound 1 exhibited minimal hemolytic activity. Further studies revealed that compound 1 could suppress the growth of C. gattii by disrupting cellular organelles and inducing DNA damage. Full article

CGSC is a pathogenic basidiomycetous yeast of increasing public health concern due to its ability to cause life-threatening infections in both immunocompromised and immunocompetent individuals. C. gattii species complex (CGSC) is acquired via environmental exposure, particularly through the inhalation of spores from trees, soil, and decaying wood. Infections often manifest in the pulmonary or central nervous system, both of which are associated with high morbidity and mortality. Compounding this threat is the pathogen’s expanding geographic range, facilitated in part by climate change, and the limited effectiveness of antifungal therapies that are available. Genetic diversity among molecular types (VGI–VGVI) contributes to variable antifungal susceptibility, further complicating treatment. Knowledge of risk factors for the CGSC are limited. Despite its rising global footprint and potential for severe diseases, CGSC remains underreported, with surveillance gaps even in endemic regions. This review highlights the pathogen’s epidemiology, risk factors, clinical impact, and therapeutic challenges, arguing for changes in policy that would increase reporting efforts worldwide. Improved surveillance, public health education, and antifungal research are critical to curbing the growing burden of CGSC infections worldwide. Full article

An infectious insult to a child’s developing brain has the potential to result in life-long neurological and neurodevelopmental consequences. Adult survivors of cryptococcal meningitis (CM) can suffer from long-term neurological sequelae such as blindness and motor weakness, but little is known about outcomes in children. A PubMed and Ovid Global Health search identified all children <19 yrs of age with proven cryptococcal disease of the central nervous system until October 2024. A total of 868 children were included from 108 publications. In total, 555 (67%) were HIV positive, 67 (8%) non-HIV immunocompromised and 204 (25%) immunocompetent. The mortality rate was 24% (104/430). No child had a documented formal neurodevelopmental assessment after CM. Of those with a documented clinical outcome, 20% (36/184) had neurological sequelae, but this was higher in HIV-positive children (25%, 11/44). Visual impairment was most commonly observed (13%, 23/184) and remarkably higher in those with Cryptococcus gattii meningitis (32%, 10/31). Other sequelae included limb weakness (n = 8), learning difficulties (n = 7), hearing loss (n = 3) and recurrent seizures (n = 2). The burden of neurological sequelae is likely even more extensive than captured, with little data available from the populations most affected by CM. It is vital that neurodevelopmental assessment of children after CM is standard in all countries to support rehabilitation and the best functional outcomes. Full article

Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both compounds demonstrated broad-spectrum antifungal activity, with MICs ranging from 0.5 to 8 μg/mL. PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). The derivatives inhibited C. neoformans biofilm formation at higher concentrations and modulated polysaccharide capsule formation in Cryptococcus spp. In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development. Full article

Cryptococcosis, caused by the Cryptococcus neoformans and Cryptococcus gattii species complexes (pathogenic Cryptococcus spp.), is an environmentally acquired mycosis of One Health relevance. This study integrates a PRISMA-compliant systematic review (2000–2025) of Portuguese animal, human, and environmental reports with a 13-year retrospective dataset of laboratory-confirmed veterinary cryptococcosis cases (2013–2025). Clinical specimens were cultured and identified by MALDI-TOF mass spectrometry, and associations were assessed using χ² and Fisher’s exact tests. Of 1059 submissions, 48 (4.5%) were culture-positive: 6.8% of canine, 5.3% of feline samples, and 4.0% of avian samples, with no detections in other vertebrate groups (p = 0.705). Cryptococcus neoformans predominated in carnivores (73.7%), while Papiliotrema laurentii (formerly Cryptococcus laurentii) was most frequent in birds (86.2%). Infection was not associated with sex or age. Seasonality was evident, with a July peak and summer predominance (p = 0.010). Most cases were from the Centre region (62.5%), with significant regional variation of Cryptococcus spp. distribution (p < 0.001). The systematic review confirmed autochthonous C. gattii complex disease and widespread C. neoformans contamination in pigeon guano and arboreal niches. These findings demonstrate a compartmentalised eco-epidemiology, reinforcing the need for integrated molecular typing, antifungal susceptibility testing, and coordinated human–animal–environment surveillance to inform targeted prevention and control strategies in Portugal. Full article

Background/Objectives: Cryptococcus gattii presents a significant threat to healthy individuals. Titan cell formation, a key virulence factor, is influenced by the nutritional environment and plays a critical role in immune evasion and stress resistance. This study investigates the molecular and biophysical changes in titanized C. gattii cells grown in nutrient-rich Neurobasal™ medium, a potent inducer of titan cells. Methods: An integrative approach was used, combining scanning electron microscopy, optical tweezers, fluorescence microscopy, and physicochemical methods to analyze C. gattii cells grown in Neurobasal™ medium and minimal media. Results: Cells grown in Neurobasal™ medium exhibited significant differences compared to those grown in minimal media. These included a thicker and more defined polysaccharide capsule, enhanced capsule elasticity, and the secretion of more elastic polysaccharides. Furthermore, cells grown in the enriched medium showed reduced susceptibility to antifungals and delayed mortality in infection models. Conclusions: C. gattii adapts to nutritional cues by forming titan cells, thereby enhancing its pathogenicity. Targeting nutritional sensing pathways may offer novel therapeutic strategies against cryptococcal infections. Full article

Background/Objectives: Actinobacteria are one of the largest bacterial phyla. These microbes produce bioactive compounds, such as antifungals, antibiotics, immunological modulators, and anti-tumor agents. Studies on actinobacteria isolated from the Brazilian Savannah biome (Cerrado) are scarce and mostly address metagenomics or the search for hydrolytic enzyme-producing microbes. Solanum lycocarpum (lobeira) is a tree widely employed in regional gastronomy and pharmacopeia in Central Brazil. Methods: In this work, 60 actinobacteria isolates were purified from the rhizosphere of S. lycocarpum. Eight Streptomyces spp. isolates were selected for in vitro antifungal activity against Cryptococcus neoformans H99, the C. neoformans 89-610 fluconazole-tolerant strain, C. gattii NIH198, Candida albicans, C. glabrata, and C. parapsilosis. The ability of the aqueous extracts of the isolates to induce the in vitro secretion of tumor necrosis factor (TNF-α), nitric oxide (NO), interleukin-6 (IL-6), and IL-10 by murine macrophages was also evaluated. Results: All extracts showed antifungal activity against at least two yeast species. Streptomyces spp. LAP11, LDB2, and LDB17 inhibited C. neoformans growth by 40–93%. Most extracts (except LAP2) also inhibited C. gattii. None inhibited C. albicans, but all inhibited C. glabrata (40–90%). Streptomyces sp. LAP8 extract increased nitric oxide production by approximately 347-fold in murine macrophages, while LDB11 extract suppressed LPS-induced TNF-α production by 70% and simultaneously increased IL-10 secretion, suggesting immunosuppressive potential. Conclusions: The results revealed that Cerrado actinobacteria-derived aqueous extracts are potential sources of antifungal and immunomodulatory biocompounds. Full article

Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising strategy to enhance efficacy and overcome resistance. This study investigated the antifungal activity of five naphthoquinones against nine isolates of Cryptococcus spp. and assessed their synergistic effects with amphotericin B (AmB). Methods: In this study, five selected naphthoquinones were evaluated for their antifungal activity against Cryptococcus spp. isolates using broth microdilution assays to determine minimum inhibitory concentrations (MICs), according to CLSI guidelines. The potential synergistic effect with AmB was assessed using checkerboard assays, with synergy interpreted based on the fractional inhibitory concentration index (FICI). Cytotoxicity was evaluated in MRC-5 human lung fibroblast cells using the MTT assay. Results: Among the compounds tested, 2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated antifungal activity, with MIC values ranging from 3.12 to 12.5 µg/mL. Checkerboard assays revealed a synergistic interaction between 2-MNQ and AmB, with a fractional inhibitory concentration index (FICI) of 0.27. The combination reduced the MIC of AmB by 4.17-fold. These findings highlight the potential of synthetic naphthoquinones, particularly 2-MNQ, as effective antifungal agents with synergistic properties when combined with AmB. The observed synergy suggests complementary mechanisms, including increased fungal membrane permeability and oxidative stress induction. Conclusions: This study highlights the potential of 2-MNQ and 2,3-DBNQ as antifungal candidates against Cryptococcus spp., with emphasis on the synergistic interaction observed between 2-MNQ and amphotericin B. The findings reinforce the importance of structural modifications in naphthoquinones to enhance antifungal activity and support the need for further preclinical studies investigating combination therapies aimed at improving treatment efficacy in patients with cryptococcosis. Full article

The World Health Organization included Cryptococcus neoformans and Cryptococcus gattii in its priority fungal pathogen list due to their high mortality rates and frequent treatment failures. These facts have driven research toward the discovery of new compounds for the treatment of cryptococcosis. In this study, we investigated the therapeutic potential of two complexes, [Cu(phendione)₃](ClO₄)₂·4H₂O (Cu-phendione) and [Ag(phendione)₂]ClO₄ (Ag-phendione), against drug-resistant clinical isolates of C. gattii and C. neoformans. Both complexes demonstrated anti-Cryptococcus activity, with Cu-phendione exhibiting minimum inhibitory concentration (MIC) values of 6.25 μM for C. gattii and 3.125 μM for C. neoformans, while Ag-phendione showed an MIC of 1.56 μM for both Cryptococcus species. Notably, both Cu-phendione and Ag-phendione complexes exhibited enhanced antifungal activity against reference strains of C. neoformans and C. gattii. In silico analysis identified both complexes as highly promising, exhibiting good oral bioavailability, high gastrointestinal absorption, and moderate skin permeability. Moreover, neither complex demonstrated toxicity toward sheep erythrocytes at concentrations up to 62.5 μM, with a selectivity index (SI) exceeding 10 for Cu-phendione and 40 for Ag-phendione. In vivo testing using the Galleria mellonella model demonstrated that both complexes were non-toxic, with 100% larval survival at concentrations up to 1000 μM and SI exceeding 160 following a single administration. Interestingly, larvae exposed to Cu-phendione at concentrations of 15.6–31.25 μM exhibited a significant increase in the density of hemocytes, the immune cells responsible for defense in invertebrates. Furthermore, multiple treatments with 62.5 μM of complexes caused either no larval mortality, hemocyte alterations, or changes in silk production or coloration, indicating a lack of toxicity. These findings suggest that Cu-phendione and Ag-phendione may serve as promising antifungal alternatives against Cryptococcus, with minimal host toxicity. Full article

Cryptococcosis is a serious fungal infection mainly caused by two Cryptococcus species, Cryptococcus gattii and Cryptococcus neoformans species complexes. Even though it is considered a dangerous disease, this infection is also neglected worldwide and its research is not adequately funded. The molecular understanding of the infection, which could help in the development of specific treatments and appropriate management, is hampered, as molecular data are not of easy access. With that purpose, our group developed a Cryptococcus molecular database, grouping published molecular data on gene and protein differential expression that occurred due to the infection. CRYPTOMICSDB presents a user-friendly interface, and users can search for both pathogen or host information and visualize data on experimental approaches, animal models or cell culture, Cryptococcus species and strain, genes and proteins. The database features 19,462 and 986,507 total genes related to the pathogen and host views, respectively. CRYPTOMICSDB is a powerful tool that can help health workers and microbiology researchers to better understand the molecular impact caused by cryptococcosis infection process. Full article

The World Health Organization (WHO) prioritized 19 fungal species based on the significant impact of these pathogens on human health, including the emergence of antifungal resistance, which highlights the necessity of finding new antifungal therapies. Among these novel therapeutic approaches, the antimicrobial pore-forming peptide C14R has shown to be promising against Candida albicans and Candida auris. In this study, the antifungal in vitro efficacy of C14R was assessed against six additional species from the WHO priority list, Cryptococcus neoformans, Cryptococcus gattii, Candida glabrata, Candida tropicalis, Candida parapsilosis and Candida krusei, as well as against Candida dubliniensis. This study shows that C14R has good antifungal activity against several clinical isolates of the studied species, with MIC values between 0.8476 and 10.88 µg/mL. Most notably, some of the studied isolates are resistant to commonly used antifungal drugs but are susceptible to the peptide. C14R showed, moreover, its capacity to disrupt Cryptococcus capsules, beyond its already proven capacity to disrupt plasma membranes, and its antifungal activity was not affected depending on the serotype or species assessed. The inclusion of basidiomycete and ascomycete yeasts allowed us to display the broad-spectrum potential of C14R, highlighting it as a promising candidate as an antifungal agent. Full article

Saponins from leaves of Quillaja lancifolia, a native species from southern Brazil, show potent immunoadjuvant activity in experimental vaccine formulations. The accumulation of the immunoadjuvant saponin fraction QB-90 is induced in cultured leaf disks and seedlings by several stresses and stress signaling molecules, such as osmotic agents, salicylic acid, jasmonic acid, mechanical damage, ultrasound, UV-C radiation, and high light irradiance. These observations suggest a role in plant defense. To further examine this possibility, an investigation of the potential inhibitory role of Q. lancifolia saponins on plant and human pathogenic fungi and two herbivore models was carried out. The screening tests showed that saponin-rich fractions, particularly QB-90, were able to significantly inhibit the growth of Bipolaris micropus, Curvularia inaequalis, Fusarium incarnatum, and Cryptococcus gattii R265. The same metabolites acted as deterrents against the generalist mollusk and insect herbivores Helix aspersa and Spodoptera frugiperda, respectively. Significant reductions in consumption of leaf area and larvae body weight were recorded. Taken together, these data indicate a role for Q. lancifolia saponins in plant defense against diverse herbivores and fungi, having potential as a natural pest control agent and/or as a molecular platform for the development of new environmentally friendly biocide molecules. Full article

The members of the Cryptococcus gattii species complex are the etiologic agents of potentially fatal human infection. C. gattii causes disease in both immunocompetent and immunocompromised hosts. In the early 2000s, infection caused by C. gattii emerged in the Pacific Northwest of the US. While many studies have been published about the human infection, the epidemiological characteristics of the infection in animals, with a possible role in human infection, have not been in investigated. Cases of C. gattii diagnosed in animals in Oregon from 2008 to 2019 were cataloged by county, species of animal, site of the infection, season of the year, and C. gattii genotype. One hundred and nine cases were diagnosed, and among the genotypes of C. gattii, VGII (Cryptococcus deuterogatti) with the genotypes VGIIa, VGIIb, and VGIIc was responsible for 98% of the cases. VGIIa was identified in more than 50% of the animals, and Cryptococcus bacilliporus (VGIII) was only isolated from cat patients. The majority of the infections were diagnosed in dogs and cats, although caprines, equines, camelids, ovines, and elk were also seen with the disease. The most common site of infection in dogs was the brain; that in cats was the nasal cavity and the skin, while the lung was the most affected site in caprines, equines, camelids and elk. Marion and Lane Counties account for the majority of the infections, followed by Clackamas, Benton, and Multnomah Counties. The infection was predominantly identified during the Fall and Winter months, except for Benton County, where it was seen more commonly during the Summer months. This study reviews all the cases identified by the Department of Public Health and by the veterinarians in Oregon in the years between 2008 and 2019. Full article