Search Results (2,039)

Background: Antifungal resistance among Candida species and related genera, coupled with the lack of new drugs, poses a significant threat to public health. Several studies have demonstrated a relationship between virulence factors and resistance. Current objectives include identifying new targets and searching for new natural molecules. Carvacrol, a natural phenolic compound, has been shown to have antimicrobial properties; however, its impact on the virulence of species other than Candida albicans and related yeast genera remains underexplored. Methods: The antifungal activity of carvacrol was evaluated against clinical isolates of Candidozyma auris, Meyerozyma guilliermondii, and Candida dubliniensis, as well as its effect on adhesion, hydrophobicity, biofilm formation and osmotic stress tolerance. In vivo activity was assessed using the Galleria mellonella infection model at MIC concentrations. Results: Carvacrol inhibited adherence and significantly reduced both early and preformed biofilms in M. guilliermondii and C. dubliniensis. In C. auris, the compound produced a modest reduction in biofilm activity but significantly enhanced larval survival in the in vivo model (~20%, p < 0.01). Carvacrol also induced increased tolerance of C. auris to osmotic stress, suggesting activation of adaptive pathways. Conclusions: Carvacrol exhibits species-specific effects, acting as an antivirulence modulator in M. guilliermondii and C. dubliniensis and attenuating virulence in vivo in C. auris. These findings support the potential of carvacrol as an adjuvant antifungal strategy, particularly against C. auris, and highlight the relevance of targeting virulence traits to reduce selective pressure and limit antifungal resistance. Full article

Currently, the increased incidence of invasive fungal infections globally is posing a significant challenge to public health. Due to drug resistance issues, the clinical efficacy of existing antifungal drugs is seriously insufficient, while new drug development progresses slowly. Consequently, there is an urgent need to discover and develop novel antifungal therapeutics. Natural products have the characteristics of wide sources and few adverse reactions and are one of the sources for developing antifungal drugs. Numerous studies have shown that many compounds isolated from plants and traditional Chinese medicine have antifungal activity and diverse antifungal mechanisms. Thymol, a monoterpene phenol compound from thyme (Lamiaceae), has multiple biological functions such as antibacterial, antioxidant, and anti-inflammatory. Recent research has found that thymol has strong antifungal activity, and its molecular mechanisms involve cell membrane rupture, interference with cell wall synthesis, disruption of mitochondrial function and energy metabolism, inhibition of biofilm, inhibition of virulence factor expression, inhibition of key enzymes, and induction of cell apoptosis. This review aimed to summarize the antifungal activity of thymol and the underlying molecular mechanisms, safety, and potential clinical applications. Emerging technologies in thymol delivery systems and future research directions are also discussed. The comprehensive analysis aims to provide a detailed understanding of fungal infections and the role of thymol in antifungal treatment, offering insights for further research and clinical practice. 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

Patients with leukemia are at heightened risk for invasive fungal infections (IFIs) due to profound immunosuppression caused by both the malignancy and its treatment. Chemotherapy-induced neutropenia, mucosal barrier disruption, and impaired innate and adaptive immune responses create a highly permissive environment for opportunistic fungal pathogens. Antifungal prophylaxis, particularly in acute myeloid leukemia (AML), has become a cornerstone in reducing IFI-related morbidity and mortality. This review outlines the immunopathogenic mechanisms underlying susceptibility to IFI and discusses current evidence on the optimal timing and therapeutic strategies for antifungal intervention. The clinical utility of key antifungal agents, namely, posaconazole, isavuconazole, and voriconazole, is critically evaluated. We also examine the potential role of emerging agents such as opelconazole, which enables targeted pulmonary delivery and prolonged epithelial retention, representing a promising approach to IFI prevention. Drug-specific considerations, including pharmacokinetics, drug–drug interactions, toxicity profiles, and cost-effectiveness, are analyzed in the context of clinical decision-making. Finally, we emphasize the importance of tailoring antifungal strategies based on leukemia subtype, immunosuppressive status, and individual patient factors to optimize outcomes and support antifungal stewardship in hematologic malignancies. Full article

(1) Background: Invasive fungal diseases (IFDs) represent significant challenges in clinical practice, particularly among immunocompromised individuals, leading to substantial morbidity and mortality. The present document aims to provide evidence-based consensus for the timely initiation of antifungal treatment, focusing on early empiric approaches among immunocompromised patients. (2) Methods: A multidisciplinary expert panel of nine healthcare professionals (HCPs) reviewed the literature, including guidelines and consensus reports (2013–2023; PubMed, Scopus). The panel defined appropriate empiric antifungal approaches for invasive candidiasis, aspergillosis, and mucormycosis among hematological and critically ill patients. Consensus was defined as ≥75% agreement. (3) Results: A total of 47 statements were included. The experts recommend that early targeted antifungal therapy is critical for high-risk patients with suspected IFDs. Empiric therapy may be initiated before definitive diagnosis, considering the local fungal prevalence and the patient’s risk category. Close monitoring is essential, and switching between antifungal classes may be necessary for patients who experience deterioration or side effects. The transition from intravenous to oral therapy depends on the specific infection, the availability of therapeutic drug monitoring, and the patient’s progress. (4) Conclusions: Implementing this targeted, early approach may improve the outcomes of vulnerable patients with IFDs. Full article

Mangrove ecosystems along the Indian Ocean coast show great biodiversity, adapting to harsh environmental conditions of high salinity and higher organic matter, and they are a host for a range of microbial communities with special features that produce unique secondary metabolites. Of this, mangrove-associated endophytic fungi, the second largest ecological group of marine fungi, show the greater potential, being a diverse pool for discovering novel bio-actives with pharmacological and biotechnological interest. This review summarizes the research findings on structural diversity and the associated pharmacological activities of secondary metabolites produced by mangrove-associated fungi along the Indian Ocean coast reported over the period of 2002–2025, based on the literature retrieved from Google Scholar. The total of 302 secondary metabolites is presented mainly from classes of polyketides (208), alkaloids (34), and terpenoids (60). Interestingly, 164 compounds were identified, as first reported in those publications. These compounds have been reported to show diverse biological activities, and the most prominent activities are cytotoxic, antibacterial, antifungal, antioxidant, enzyme inhibitory, and anti-inflammatory effects. The structural novelty and pharmacological activities of these metabolites highlight the importance of mangrove fungi as promising sources for new drug discovery and advancing industrial biotechnology. Therefore, this review highlights the insight into the possible application of these chemical compounds in the future drug industry, as well as in biotechnology for advancing human well-being. Furthermore, though significant progress has been made in exploring the fungi community from mangroves of the African and Middle Eastern coasts, the Indian coast mangrove fungi are yet to be explored more for novel discoveries. Full article

Invasive Candida infections in the neonatal intensive care unit (NICU) are associated with significant morbidity and mortality, particularly among extremely preterm neonates. Early treatment with antifungals is critical to improve survival rates and avoid long-term adverse outcomes. Prevention with antifungal prophylaxis in high-risk neonates has been shown to reduce the prevalence of invasive Candida infections effectively. However, the irrational and/or inappropriate use of antifungals has been documented. This narrative review aims to provide an overview of the rationales for the inappropriate use of antifungals in the NICU, the consequences that ensue, and the promising strategy of antifungal stewardship programs to optimize antifungal use. The nonspecific clinical presentation of systemic Candida infections and the lack of rapid, accurate diagnostic techniques for Candida identification and specification in most settings lead to a high rate of empirical treatment in neonates without a proven infection. Moreover, evidence on the optimal dosing of antifungal agents and the treatment duration in the neonatal population is lacking, which may result in excessive or subtherapeutic drug exposure. Antifungal misuse is associated with microbiological consequences, including the emergence of antifungal-resistant Candida strains, and clinical consequences, such as drug toxicities and alterations in the intestinal mycobiome. It is therefore imperative to optimize antifungal use in the NICU. The implementation of antifungal stewardship programs, which, through a multidisciplinary approach, aim to improve diagnosis and guide clinicians on antifungal selection, dosing, and duration for both prevention and treatment according to the local epidemiology, represents a promising strategy for antifungal optimization in the NICU. Full article

Ellagic acid (EA), a naturally occurring phenolic compound, has garnered significant interest as a potential antifungal agent owing to increasing fungal resistance and a scarce therapeutic pipeline. This review consolidates the evidence of the broad-spectrum activity of EA against critical priority pathogens, including Candida auris and Cryptococcus neoformans. We highlight its multi-target mechanisms of action, such as the impairment of cell wall integrity and plasma membrane disruption resulting from the inhibition of ergosterol biosynthesis, and inhibition of key enzymes, such as laccase. In addition to its direct growth-inhibitory effects, EA exhibits antivirulence properties, reducing biofilm formation and hyphal morphogenesis. Notably, it demonstrates synergistic potential with conventional antifungals, such as fluconazole, enhancing efficacy and potentially hindering the emergence of resistance. Although its poor solubility and bioavailability pose therapeutic challenges, advanced formulations such as liposomal systems show promise for improving its delivery. We conclude that EA is a promising candidate for developing new antifungal strategies, particularly as a synergistic agent or in nanoformulations, warranting further investigation to translate its potential into clinical practice. Full article

Diseases associated with yeast pathogens have become an increasingly serious global health issue. The range of virulence factors and the development of mechanisms of resistance have posed a significant challenge in the fight against these types of infections. Lectins, proteins capable of reversibly binding to carbohydrates and glycoconjugates, have been assessed as antifungal agents. This review shows that lectins have demonstrated versatility and significant potential as therapeutic agents against Candida, Nakaseomyces and Cryptococcus. These molecules act through diverse mechanisms, including disruption of fungal cell membranes, induction of oxidative stress, inhibition of ergosterol biosynthesis, and interference with mitochondrial and lysosomal functions. Some lectins have been shown to inhibit yeast-to-hyphae morphological transitions and biofilm formation, which are critical virulence factors for pathogenic yeasts. Moreover, some lectins have shown potential to enhance the efficacy of conventional antifungal drugs through synergistic interactions, though these effects can depend on the fungal isolate. Beyond in vitro activity, translational considerations remain underdeveloped in the context of antifungal applications of lectins. Some lectins exhibit minimal toxicity, while others require careful dosing due to potential toxicity or undesired immunogenicity. Delivery and stability also present challenges, though strategies such as chemical modifications and topical, mucosal, or nanoparticle-based formulations show promise. Overall, the multifaceted antifungal activities of lectins highlight their promising role as innovative candidates in the development of novel therapies to address the growing challenge of yeast pathogen resistance. However, significant knowledge gaps persist, highlighting the urgent need for coordinated research that bridges in vitro findings with practical pharmacological applications. Full article

Polyelectrolyte microspheres based on a polymer containing sulfonate groups are considered promising drug delivery systems for encapsulating drugs and ensuring their prolonged release. In this study, gel microparticles based on various sulfonate-containing polymers were formed, and their potential as drug delivery systems was evaluated, particularly for the controlled administration of the cytotoxic anthracycline antibiotic doxorubicin and the antifungal drug fuchsine. An undeniable advantage of such gel microspheres is the presence in their structure of sulfonate groups localized both in the surface layer and in the volume. The main monomers used were styrene-4-sulfonic acid sodium salt and 3-sulfopropyl methacrylate potassium salt; spherical, porous microparticles were obtained via free-radical reverse suspension polymerization. Microsphere properties (size, porosity, pore structure, electrical surface properties, and swelling) were tailored by changing the nature of the sulfonate, using a comonomer (vinyl acetate or ethyl acrylate), adding a co-solvent, or modulating the crosslinker composition, which influenced drug loading efficiency (doxorubicin, fuchsine). The gel-like structure of the microspheres was confirmed, and the sulfonate groups were found to be distributed throughout both the surface layer and the internal volume of the microspheres. A comparison was also made with non-porous polymer particles containing sulfonate groups. The sorption capacity of the gel microspheres for doxorubicin was 2.2 mmol/g, significantly higher than the 0.4 mmol/g observed for the non-porous reference particles. The obtained values of doxorubicin sorption on gel microspheres are over 60 times higher than the values reported in the literature. Full article

Natamycin, a polyene macrolide antifungal, has long been used as a food preservative and is the only Food and Drug Administration (FDA)-approved topical treatment for fungal keratitis. While its safety is supported by specific ergosterol interaction and minimal systemic absorption, current research mainly focuses on short-term effects, often overlooking long-term, developmental, and microbiome-related impacts. In food applications, questions remain about cumulative exposure and potential disruptions to gut microbiota. For ophthalmology, advanced delivery methods like nanocarriers and hydrogels enhance drug penetration but may alter pharmacokinetics and pose formulation challenges. Regulatory approvals have historically depended on established safe use and limited toxicological data, emphasizing the need for more systematic evaluations. Zebrafish (Danio rerio) represent a promising yet underutilized model for addressing significant gaps in research, particularly in the realms of microbiome studies, ocular health, developmental processes, and multigenerational effects. When paired with omics technologies, zebrafish facilitate comprehensive system-level mapping of drug-induced outcomes. This review consolidates existing evidence and positions zebrafish as a vital translational link between in vitro assays, mammalian models, and clinical practice. Additionally, it proposes a framework to ensure the effective and scientifically supported use of natamycin in both food and medicinal applications. Full article

Cutaneous infections caused by dematiaceous fungi are rare in the general population but are increasingly recognized in solid organ transplant recipients as a consequence of prolonged immunosuppression. When Alternaria species are confirmed as the causative agents of a skin infection, the condition is referred to as alternariosis. These infections may clinically resemble bacterial or neoplastic lesions and require accurate diagnosis and individualized therapy. We report one case of cutaneous alternariosis in a kidney transplant recipient receiving tacrolimus-based immunosuppression. The patient was a 47-year-old woman who sustained minor trauma to her knee three months after transplantation. She developed an ulcerated, crusted lesion, which coincided with severe neutropenia. Histology, culture and molecular identification confirmed A. infectoria. Treatment included systemic azole therapy (voriconazole followed by isavuconazole) and surgical excision, resulting in resolution without recurrence. This case highlights the importance of early recognition of alternariosis in transplant recipients. Successful management typically requires combined surgical and systemic antifungal therapy, with careful monitoring of drug interactions and immunosuppressive levels to prevent toxicity or rejection. Full article

Candida albicans, a commensal and opportunistic fungal pathogen, is a major clinical concern due to its ability to cause infections ranging from mild mucosal conditions to life-threatening systemic diseases, particularly in immunocompromised patients. Its capacity to form biofilms on medical devices further complicates treatment by enhancing antifungal resistance and immune evasion. In the search for novel therapeutic strategies, the lysine-enriched amphibian-derived temporin B analog, TB_KKG6K, has emerged as a promising antifungal agent. This study demonstrates that TB_KKG6K exhibits potent fungicidal activity against planktonic C. albicans cells, with a low potential to induce adaptation or resistance. TB_KKG6K has no adverse impact on the anti-Candida efficacy of standard antifungal drugs when applied in combination, interacting additively with amphotericin B and caspofungin in a fungicidal mode of action. Additionally, TB_KKG6K effectively reduces biofilm maturation on silicone elastomers, a material commonly used in medical devices, further highlighting its therapeutic potential. These data together with our previous documentation of minimal cytotoxicity and irritation potential in human cells makes TB_KKG6K a strong candidate for combating both planktonic and biofilm-associated C. albicans infections. These findings underscore the dual efficacy of TB_KKG6K and its potential to address the challenges posed by C. albicans in clinical settings. Full article

This study evaluated the in vitro interaction of 5-fluorouridine (5-FUrd) with antifungal drugs and examined the role of efflux pumps in 5-FUrd resistance. Eleven reference Candida strains and twenty-three clinical C. albicans isolates from gynecological patients were tested. The antifungal activity of 5-FUrd alone and in combination with amphotericin B, fluconazole, voriconazole, caspofungin, and flucytosine was assessed using the checkerboard microdilution method. Efflux pump activity was evaluated using two inhibitors: carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and verapamil. 5-FUrd exhibited antifungal activity against both the reference and clinical Candida strains, with MIC values ranging from 0.1 µg/mL to 409.6 µg/mL. The checkerboard assays revealed primarily no interactions in the reference Candida strains, whereas the reference C. albicans and clinical C. albicans isolates showed notable synergy between 5-FUrd and fluconazole, voriconazole, or caspofungin. The efflux pump inhibitors reduced the MICs of 5-FUrd in the resistant strains of C. lusitaniae, C. kefyr, and particularly C. krusei, suggesting efflux-mediated resistance mechanisms. This study highlights the potential of 5-FUrd, alone or combined with azoles or caspofungin, as an adjunct therapy against Candida infections. It also suggests that reduced susceptibility may be linked to efflux pump activity in certain strains. Full article

Fungi constitute a diverse kingdom of eukaryotic organisms with remarkable adaptability, ranging from saprophytic decomposers to lethal human pathogens. This review synthesizes current insights into fungal adaptations that underline pathogenesis, focusing on enzymatic strategies including hydrolytic enzymes, metabolic and physiological plasticity such as thermotolerance and nutrient flexibility, and evasion of host immunity via mechanisms like melanin production and biofilm formation. We detail fungal survival tactics including spore formation and genomic and epigenetic plasticity, which contribute to resilience and evolution under environmental and host-imposed stresses. The escalating emergence of antifungal resistance and the global impact of environmental changes underscore urgent clinical challenges. Advances in diagnostics, novel therapeutics incorporating AI-assisted drug discovery, and integrated One Health approaches are poised to combat this growing threat. This comprehensive overview aims to guide future research and inform clinical management of fungal infections in an era of dynamic microbial evolution and environmental upheaval. Full article