Search Results (118)

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

Vulvovaginal candidiasis (VVC) represents a widespread gynaecological challenge, affecting approximately 75% of women at some point during their reproductive years, with a significant subset progressing to recurrent forms (RVVC). Classical azoles and polyenes remain the cornerstone of therapy. However, their clinical utility is undermined by the rise of azole-resistant non-Candida albicans species, the capacity of Candida to form biofilms, and a complex variety of host-related factors that complicate disease expression and therapeutic response. This narrative review provides a critical up-to-date examination of the therapeutic landscape, integrating current diagnostic algorithms with pharmacological strategies for both acute, recalcitrant and recurrent VVCs. We assess the efficacy and safety of established antifungal agents alongside the breakthrough introduction of novel drug classes, with a particular interest in the oral triterpenoid ibrexafungerp and the tetrazole oteseconazole, which offer new mechanisms of action for cases that fail to respond to standard regimens. Furthermore, we address the management of a special clinical scenarios, including pregnancy and lactation, and explore promising emerging innovative approaches such as mucoadhesive formulations, immunomodulatory approaches, and alternative non-antifungal therapies. Ultimately, this review aims to support clinical decision-making by balancing the accessibility and user-friendliness of conventional treatments with the targeted precision offered by modern antifungal agents. Full article

The continuous release of pharmaceutical compounds into aquatic environments poses significant challenges to environmental sustainability, as conventional wastewater treatment plants are often ineffective in removing recalcitrant and bioactive molecules. In this study, the adsorption performance of nanoclay was systematically evaluated for the removal of nystatin, a polyene antifungal of emerging environmental concern, from aqueous solutions. The effects of solution pH, adsorption kinetics, equilibrium isotherms, and adsorption mechanisms were investigated under environmentally relevant conditions. Nanoclay exhibited outstanding removal efficiency, exceeding 98% across a wide pH range (3–11), thereby demonstrating strong operational robustness and minimal sensitivity to pH variations. Structural and spectroscopic analyses (XRD and FTIR) confirmed that adsorption occurred predominantly on the external surface of the nanoclay, without significant disruption of its lamellar structure, and was governed mainly by hydrophobic interactions and hydrogen bonding. Kinetic data were best described by the pseudo-second-order model, with rapid equilibrium achieved within approximately 20 min, indicating high affinity between nystatin and the adsorbent surface. Equilibrium data were best fitted by the Sips isotherm model, reflecting surface heterogeneity and a favorable adsorption process, with a high maximum adsorption capacity of approximately 911 mg/g. A preliminary cost analysis revealed low raw material costs, while energy consumption, particularly during drying, was identified as the main economic limitation. Overall, the results highlight Nanoclay as an efficient, robust, and promising adsorbent for the sustainable removal of hydrophobic pharmaceutical contaminants from water and wastewater. Full article

Among Candida species, several are major opportunistic fungal pathogens capable of causing a wide spectrum of infections, ranging from superficial mucosal conditions to severe systemic diseases. Their success as human pathogens is largely due to their ability to rapidly adapt to diverse host environments and develop resistance to antifungal agents. Experimental evolution provides a powerful framework for understanding these adaptive processes by observing evolutionary change in real-time. Although most studies rely on in vitro systems and a limited set of Candida species, there is strong evidence that genome plasticity, including aneuploidy, loss of heterozygosity, and copy number variation, plays a central role in driving rapid adaptation. Experimental evolution has also been applied to study the dynamics of antifungal resistance, particularly to azoles, although relatively fewer studies have explored resistance to echinocandins and polyenes. This review summarizes current knowledge on experimental evolution in pathogenic Candida species, with a focus on genome plasticity, adaptation to host-imposed stress, and particularly on the emergence of antifungal resistance. It also identifies critical research gaps, including the need for broader species coverage, investigation of underexplored antifungal classes, and evaluation of combined therapies. A deeper understanding of these dynamics is essential to improve antifungal strategies and counter the growing threat of drug-resistant Candida spp. infections. Full article

Rice blast, caused by the fungus Magnaporthe oryzae, is a devastating disease that threatens global food security, causing annual yield losses of 10–30%. Consequently, novel control strategies beyond conventional fungicides are urgently needed. Tetramycin, a polyene macrolide antibiotic, is known for its broad-spectrum antifungal activity. However, the specific mechanisms underlying its efficacy against rice blast remain to be fully elucidated. In this study, we demonstrate that tetramycin confers resistance through a dual mode of action. First, in vitro assays revealed that tetramycin directly inhibits M. oryzae mycelial growth. Second, and more critically, it functions as a potent immune elicitor in Oryza sativa. Transcriptome analysis coupled with physiological assays showed that tetramycin treatment triggers a rapid oxidative burst, characterized by significantly elevated activities of key defense enzymes, including superoxide dismutase, peroxidase, phenylalanine ammonia lyase, and polyphenol oxidase (PPO). This oxidative response is further orchestrated through the simultaneous activation of the jasmonic acid (JA) and salicylic acid (SA) signaling pathways, as evidenced by the distinct upregulation of their respective biosynthetic genes and hormone levels. Collectively, these findings indicate that tetramycin not only acts as a direct fungicide but also primes the rice innate immune system via a synergistic reactive oxygen species-JA-SA signaling network, offering a sustainable strategy for rice blast management. Full article

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such as cardiotoxicity, associated with impurities like RT6 (albonoursin). The fundamental analytical techniques for quality control are outlined. Furthermore, the clinical applications and combination therapy strategies of nystatin in treating oral diseases, vaginitis, and otitis externa are summarized in detail. Regarding biosynthesis, the assembly mechanism of nystatin A₁ via the type I polyketide synthase pathway and its subsequent modification processes are thoroughly discussed. Emphasis is placed on the latest advances and potential of gene-editing technologies, particularly CRISPR/Cas9, in the targeted knockout of genes responsible for toxic components and in optimizing production strains to enhance nystatin yield and purity. Finally, this review prospects the future development of nystatin towards improved safety and efficacy through structural optimization, innovative delivery systems, and synthetic biology strategies, aiming to provide a reference for its further research and clinical application. 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

Coccidioides immitis and C. posadasii are the causative agents of coccidioidomycosis (CM) or Valley Fever, endemic to the alkaline deserts of North and South America. Clinical treatment of CM is predominantly limited to the triazole and polyene drug classes. There are limited therapeutic options for the treatment of CM, most commonly requiring prolonged courses of therapy with established antifungal agents such as azoles and Amphotericin B, which often lead to toxicity and drug resistance. Clearly, there is a need to develop novel and better antifungal drugs against CM. This review examines both repurposed and recently discovered compounds in various stages of development for the treatment of CM. Full article

Amphotericin: B (AmpB)-resistant Candida (C.) species, such as C. parapsilosis, are among the most common causes of invasive fungal infections, posing significant challenges in hospital settings. Although AmpB is considered the first-line treatment owing to its broad-spectrum fungicidal activity, its use is hampered by severe side effects and the emergence of acquired resistance, particularly in C. parapsilosis, which exhibits reduced susceptibility to polyene, azole, and echinocandin-based antifungal drugs. Here, we present findings on photodynamic therapy (PDT) that targets the opportunistic fungal pathogens C. parapsilosis and C. albicans via the use of photosensitizers from the iodocyanine and newly developed iodinated Methylene blue families. These compounds contain heavy iodine atoms that increase the production of reactive oxygen species (ROS), the agents responsible for oxidative cellular damage, via the heavy-atom effect, which promotes intersystem crossing (ISC) and triplet-state formation. A strong antifungal effect was observed against AmpB-resistant C. parapsilosis, indicating a correlation between the quantum yield of ROS generation and the photosensitizing efficacy under near-infrared (NIR) light irradiation. The combination of efficient cellular uptake and enhanced ROS generation positions iodinated photosensitizers as promising candidates for the treatment of drug-resistant Candida strains. Full article

This study presents a model investigation into the development of tolerance to polyene antifungal drugs (nystatin and natamycin) in strains of Malassezia pachydermatis. This species, commonly associated with external ear canal infections in dogs, has emerged as increasingly significant in the broader context of growing fungal resistance to treatment. In the experiment, 10 strains of M. pachydermatis were passaged over a period of 105 weeks on media containing sublethal concentrations of nystatin and natamycin. Minimal inhibitory (MIC) and minimal fungicidal concentration (MFC) values were regularly assessed to monitor tolerance development. The results revealed a varied response among the strains: Some were eliminated during the process, while others showed a gradual increase in MIC values, up to fivefold in the case of nystatin. In several strains, acquired resistance remained stable even after passaging in drug-free conditions, whereas others reverted to their original susceptibility. The model demonstrated that resistance does not emerge immediately; significant changes appeared only after 30–45 passages. The authors propose this model as a valuable tool for tracking sequential changes that lead to resistance development. Such an approach may support targeted therapy development and help identify strains predisposed to drug adaptation. These findings hold promise for assessing therapeutic risk in immunosuppressed patients and for building resistance datasets that can support artificial intelligence algorithms in predicting fungal resistance mechanisms. Full article

Candida spp. are common components of normal microbiota in the oral cavity. However, Candida albicans can be a primary cause of superficial infections in the oral cavity and esophagus, especially in immunocompromised individuals. While these infections are rarely life-threatening, they can significantly impair quality of life and, in severe cases, progress to hematogenous dissemination. Oral candidiasis often exhibits as pseudomembranous, erythematous (atrophic), chronic hyperplastic, denture stomatitis, or angular cheilitis. Esophageal candidiasis is typically diagnosed by upper endoscopy, which involves histological examination and brushing. Clinical guidelines recommend topical antifungal agents for mild oral candidiasis, and systemic agents for moderate-to-severe disease or when topical therapy fails. However, azole antifungals pose a substantial risk of drug–drug interactions, primarily due to the inhibition of cytochrome P450 enzymes and drug transporters, which dramatically alters the pharmacokinetics of co-administered drugs. Additionally, amphotericin B, a polyene macrolide antibiotic, may cause nephrotoxicity and electrolyte disturbances (e.g., hypokalemia and hypomagnesemia). Moreover, the co-administration of nephrotoxic drugs may augment the toxicity associated with amphotericin B. Therefore, this review aimed to provide a comprehensive overview of the management of oral and esophageal candidiasis from the viewpoint of clinical pharmacology, with a particular focus on drug–drug interactions and adverse effect profiles. Full article

Oral Candida infections result from the overgrowth of this opportunistic fungus in the oral mucosa. Risk factors include immunosuppression, antibiotic or corticosteroid use, xerostomia, and conditions such as diabetes mellitus. Fungal resistance in Candida spp. has become a significant challenge, especially due to the excessive use of conventional antifungals such as azoles, echinocandins, and polyenes. Therefore, this study aims to determine the spectrum of antifungal activity of Juglans regia and assess its cytotoxicity on hepatocytes. Thus, a broth microdilution test was conducted according to the CLSI (M27-A3) guidelines. After initial screening, biofilm tests were conducted using the crystal violet (CV) and metabolic activity assays (MTT). Cytotoxicity was evaluated on human hepatocytes (HEPG2). The J. regia extract showed dose-dependent antifungal activity. At a concentration of 200 mg/mL, inhibition was greater according to the CV test in Candida albicans (31%) and Candida tropicalis (30.4%), while the MTT assay indicated a greater reduction in viability in C. albicans (61%) and C. glabrata (53.5%). At 100 mg/mL, C. albicans remained sensitive (37.7% CV; 71.6% MTT), while C. krusei and C. dubliniensis showed low viability by MTT (18.4% and 11.8%, respectively). At 50 mg/mL, C. albicans remained affected (74.3% MTT), but C. krusei, C. dubliniensis, and C. guilliermondii showed the lowest viability values (≤19.4% MTT), suggesting greater sensitivity to lower concentrations. These results indicate variation in susceptibility between species, with C. albicans being consistently inhibited, while C. krusei and C. dubliniensis responded better to lower doses. The extract showed cytocompatibility when applied to human hepatoma cells (HEPG2) and therefore holds significant potential for developing a new therapeutic approach. Full article

Invasive fungal infections (IFIs) are one of the most significant public health challenges worldwide. Yet, research and communication thereof were left behind for a long time, until the WHO published a priority pathogens list to guide research, development, and public health action in October 2022. Indeed, due to the rising number of immunocompromised patients at risk and the high level of morbidity, mortality, and economic burden they entail, especially in low- and middle-income countries, IFIs are a serious public health threat. Fungal infections due to dimorphic fungi face additional challenges such as limited knowledge outside of endemic areas and restricted availability of antifungal molecules in areas affected by these infections. The number of related deaths per year is estimated at 2.5 million, but non-governmental organisations make a wider estimation, due to the difficulties in early in vitro diagnostic and troublesome collection and analysis of epidemiological data. Despite this fact, the therapeutic toolbox addressing these infections remains limited, with only four main families of molecules available so far. The antifungal therapeutic supply is composed of very toxic polyenes, the weakly selective and nearly unused 5-fluorocytosine, and azoles, some of which are becoming increasingly inefficient against IFIs. In the 2000–2020s, the fourth arising family consisted of safer semisynthetic echinocandins. Unfortunately, nowadays, more and more fungal isolates encountered in intensive care units exhibit a low susceptibility to echinocandins or are even multiresistant. In this review, we expose the current treatments available to fight against invasive fungal infections. We recall the discovery and physico-chemical aspects of these substances leading to structure/activity and structure/properties relationships. We particularly focus on the to-date resistances and their molecular mechanisms. We finally list some of the most relevant antifungal drug candidates, as they were freshly overviewed by the World Health Organization in April 2025, highlighting the importance of the molecular dimension of this pursuit toward the expansion of the antifungal therapeutic toolbox. Full article

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of “One Health” strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy. Full article

Fusariosis is an infection caused by the fungus Fusarium spp., which is pathogenic to both plants and humans. The disease presents several clinical manifestations and epidemiological patterns. Current treatment relies on azoles and polyenes, but increasing antifungal resistance requires the exploration of new therapeutic options. This study reviewed patents related to the treatment of Fusariosis from the last 15 years (up to June 2023). The search identified 318 patents, categorized by identification code, publication date, type of application and mechanism of action, using the International Patent Classification and Cooperative Patent Classification systems. In addition, we conducted a bibliographic search in the PubMed database using the same criteria to identify the number of scientific articles. Of the 318 patents, 21 targeted Fusarium infections in humans. The years 2014 and 2018 stood out with three patents each, while the same period recorded an average of 58 published articles. The patents addressed mechanisms such as drug delivery, gene expression, immunotherapy, engineered drugs, and novel compounds. This research highlights the urgent need for continued innovation in therapeutic technologies to effectively treat Fusarium wilt. Full article