Search Results (141)

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 search for novel antiviral agents against Newcastle disease virus (NDV) remains a priority in industrial poultry farming due to the virus’s high contagiousness and associated economic losses, prompting evaluation of polyene macrolides as potential therapeutic candidates. We employed a comprehensive approach combining computational modeling (molecular docking and dynamics simulation) and laboratory experiments to investigate the antiviral potential of natamycin, nystatin, and filipin complex against three NDV strains. Molecular docking analysis indicated binding sites for macrolides within the hydrophobic regions of surface glycoproteins HN and F, with binding energies ranging from −6.5 to −10.5 kcal/mol, while 50 ns molecular dynamics simulation confirmed complex stability. Laboratory testing using fluorescence-based neuraminidase assays demonstrated dose-dependent inhibitory activity with IC₅₀ values of 0.0043 ± 0.0015 mg/mL for filipin complex, 0.0117 ± 0.0029 mg/mL for nystatin, and 0.0220 ± 0.0138 mg/mL for natamycin, with similar ranking observed for fusion inhibition (EC₅₀ values of 0.00053 ± 0.00039, 0.00545 ± 0.00560, and 0.01196 ± 0.00965 mg/mL, respectively). While filipin complex exhibited the highest antiviral activity, its significant cytotoxicity limits therapeutic application, whereas natamycin demonstrated a favorable safety profile consistent with its GRAS status. These findings indicate that natamycin exhibits a favorable safety-to-efficacy profile in vitro, warranting further in vivo investigation to clarify its mechanism of action and establish practical application protocols for NDV control in poultry. Full article

Yeasts have attracted increasing attention as potential alternatives to traditional bacterial probiotic strains due to their physiological resilience and functional versatility. However, the probiotic potential of yeast strains associated with Mexican cocoa bean fermentation remains largely unexplored. Therefore, this study aimed to conduct a preliminary screening of physiological and surface-related traits associated with probiotic functionality in four autochthonous Saccharomyces cerevisiae strains (YCTA5, YCTA9, YCTA14, and YCTA16), previously isolated from cocoa fermentation, using Saccharomyces boulardii (Jarrow Formulas^®) as a reference strain. Evaluated parameters included tolerance to temperature, pH, and bile salts; hemolytic activity; survival in vitro under gastrointestinal (GI) conditions; bile salt hydrolase activity; auto-aggregation; co-aggregation; hydrophobicity; and response to antifungal agents (fluconazole, ciclopirox, nystatin, and clotrimazole). All yeast strains grew at 37 °C and at pH 4–8 and showed no hemolytic activity. All strains exhibited high auto-aggregation (>70%) and hydrophobicity values ranging from 55 to 88%. In the coaggregation assay, strains YCTA9, YCTA14, and YCTA16 showed moderate interactions with Escherichia coli, Bacillus cereus, and Listeria innocua, with some combinations exceeding 50%. Nevertheless, none of the yeast strains exhibited measurable growth at pH 2; bile salt tolerance was limited to 0.1% Oxgall, and viability decreased by approximately 54–56% after simulated gastrointestinal transit. These findings indicate that although some strains exhibited promising surface-related properties, significant physiological constraints restrict their probiotic potential under the tested conditions. Therefore, the studied yeast strains should be regarded as preliminary candidates requiring further validation. This work provides a first-stage evaluation for identifying functional yeast strains from Mexican cocoa bean fermentation, serving as a basis for future in vitro and in vivo studies. Full article

In this study, we investigated the antifungal potential of methanolic extracts and essential oils obtained from five medicinal plants (Salvadora persica, Mentha spicata, Achillea millefolium, Matricaria chamomilla, and Zingiber officinale) against 25 clinical isolates of Candida albicans collected from patients with denture stomatitis. Antifungal susceptibility was assessed using broth microdilution as the primary method, with agar diffusion assays performed to provide complementary visual confirmation. Nystatin was included as a reference control. Across the tested samples, essential oils consistently showed stronger antifungal effects than the corresponding methanolic extracts. Notably, Z. officinale essential oil exhibited the highest level of activity, inhibiting 15 out of 25 isolates and, in several cases, demonstrating efficacy comparable to or exceeding that of nystatin. Chemical profiling by GC–MS indicated that the ginger essential oil was dominated by sesquiterpene and monoterpene hydrocarbons, with zingiberene (21.49%) being the major constituent, followed by β-sesquiphellandrene, α-curcumene, sabinene, and α-citral. This terpene-rich composition may contribute to the observed antifungal activity, potentially through the disruption of fungal cell membrane integrity. Taken together, these results suggest that Z. officinale essential oil represents a promising natural antifungal candidate for the management of denture-associated C. albicans infections. Further studies, including biofilm-based assays and in vivo evaluations, will be necessary to confirm its clinical applicability. To the best of our knowledge, this study is among the first to comparatively assess these five medicinal plants against clinical C. albicans isolates derived specifically from denture stomatitis patients. Full article

Propolis is a bee product with a complex chemical composition that exhibits remarkable antifungal activity against C. albicans and can inhibit resistant biofilms thanks to its content of compounds such as flavonoids and phenolic acids. Its efficacy varies depending on its geographic origin: European propolis inhibits the initial formation of biofilms, while Brazilian propolis is superior at inhibiting mature biofilms. This product also possesses fungicidal and fungistatic properties comparable in efficacy to conventional drugs, such as nystatin, fluconazole, and chlorhexidine. The use of nanotechnology, such as nanoparticles or nanorods, has overcome the low solubility of propolis compounds, improving their bioavailability and reducing cell adhesion and hyphal formation. Moreover, the integration of propolis into dental materials demonstrate its versatility for preventing recurrent infections. The study of isolated compounds such as pinocembrin, galangin, and chrysin has facilitated the identification of specific mechanisms of action, and the application of molecules such as guttiferone E in photodynamic therapies and the discovery of quorum-sensing inhibitors, such as kaempferol, using in silico models have opened new avenues for blocking yeast communication and virulence. These findings position propolis as a multifaceted and promising therapeutic alternative, although there is a need to optimize formulations to ensure clinical safety and biocompatibility. In this review, we analyze research published around the world over the last 15 years on the effects of propolis against C. albicans biofilms. Full article

Endocrine therapy is the mainstay for estrogen receptor (ER) α-positive breast cancer (BC), yet many patients display acquired resistance. We then screened natural compounds using human ERα-positive BC cells and identified perillyl alcohol (POH), a monoterpene from perilla, that reduces ERα protein levels. Chemoproteome analysis using POH-immobilized nanomagnetic beads revealed adenine nucleotide translocase 2 (ANT2), a mitochondrial inner membrane protein, as a direct target of POH. Molecular dynamics (MD) simulations predicted POH binding to the central pore of ANT2, which functions in ATP transport. ANT2 depletion reduced ERα levels, and public datasets indicate that high ANT2 expression correlates with poor prognosis in ERα-positive BC. POH also inhibited the growth of Tamoxifen- and Fulvestrant-resistant BC cells. RNA sequencing showed that fatty acid elongation-related genes were upregulated in Fulvestrant-resistant cells but downregulated by ANT2 depletion. Both ANT2 depletion and POH treatment led to the accumulation of intracellular lipid droplets in Fulvestrant-resistant cells, consistent with impaired fatty acid elongation. Finally, in silico screening using MD simulations identified venetoclax and nystatin as potential ANT2 pore binders. Both compounds reduced ERα levels in ERα-positive BC cells and increased lipid droplet formation in Fulvestrant-resistant cells. These findings highlight ANT2 as a druggable target against endocrine-resistant BC. Full article

Candida species can shift from commensal organisms to opportunistic pathogens. Both Candida albicans and non-albicans Candida (NAC) species colonize oral biofilms and periodontal pockets, where they may contribute to inflammation and the progression of periodontal disease. This study aimed to determine the prevalence and antifungal susceptibility profiles of Candida species in individuals with different stages of periodontal disease. A cross-sectional study was conducted in 100 participants whose periodontal status was clinically evaluated. Saliva samples were cultured on chromogenic agar for yeast isolation, species identification was confirmed by MALDI-TOF MS, and antifungal susceptibility to fluconazole, clotrimazole, nystatin, and amphotericin B was assessed. Candida spp. was detected in 35% of participants, where C. albicans was the most prevalent species, followed by Nakaseomyces glabratus (formerly Candida glabrata), Candida parapsilosis, Candida dubliniensis, and Candida tropicalis. Species distribution varied according to periodontal status, with N. glabratus predominating in early periodontitis and C. albicans appeared more frequently in higher severe stages of periodontitis. Susceptibility testing showed resistance of C. albicans to clotrimazole (63.6%) and nystatin (22.7%), whereas amphotericin B and fluconazole remained effective. NAC species, particularly N. glabratus, exhibited resistance to nystatin and variable resistance to clotrimazole but remained susceptible to amphotericin B. These findings underscore the importance of early detection and personalized antifungal strategies for managing periodontal disease complicated by Candida colonization. Full article

Boron is a chemically distinctive bioelement whose electron-deficient structure enables reversible coordination with oxygen-rich functional groups such as diols and hydroxyls. This property allows boron to modulate molecular stability, conformation, and biological reactivity, giving rise to both beneficial pharmacological effects and toxicological outcomes. This review examines the dual biological role of boron through the framework of bioactive boron-containing natural products and natural compounds capable of forming reversible boron complexes. Particular attention is given to naturally occurring boron-containing antibiotics, including the polyketide macrodiolides boromycin, aplasmomycin, tartrolons, and hyaboron, where boron plays a direct structural and functional role in antimicrobial activity. These compounds demonstrate how boron coordination can influence ion transport, membrane interactions, and molecular assembly, contributing to potent antibacterial properties. Beyond intrinsically boron-containing metabolites, many natural antibiotics and toxins possess oxygen-rich architectures capable of forming transient borate complexes through vicinal 1,2-diol motifs. Examples include polyene macrolide antibiotics such as amphotericin B, fungichromin, and nystatin, as well as tetracyclines, rifamycins, and macrolides such as sorangicin A, where boron coordination may affect solubility, aggregation, ionophoric behavior, and biological selectivity. Similar chemistry is observed in marine neurotoxins and polyether toxins—including tetrodotoxin, saxitoxin derivatives, azaspiracids, pectenotoxins, ciguatoxins, and gambierones—whose hydroxyl-rich frameworks enable reversible interactions with boron species present in seawater. Such complexation may enhance aqueous stability and contribute to trophic transfer and bioaccumulation within marine ecosystems. By framing boron as a molecular “double edge,” this review integrates chemical, biological, and environmental perspectives to highlight how boron coordination can simultaneously enhance antimicrobial activity while influencing toxicity and ecological persistence. Recognizing the role of boron in shaping the activity of natural products provides new insight into antibiotic function, toxin behavior, and the broader impact of boron chemistry in biological systems. 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

Background/Objectives:  Candida infections constitute a significant category of healthcare-associated infections. In studies aiming to develop new antifungal agents against Candida species, the importance of their virulence factors has been emphasized. Methods: This study included 100 Candida isolates obtained from patients hospitalized in intensive care units. Standard microbiological and molecular methods were employed for species identification. Virulence factors were determined through protease, phospholipase, hemolysis, and biofilm activity assays per-formed on the Candida strains. The EUCAST liquid microdilution method was used to assess antifungal susceptibility. Results: Based on sequencing results, 39 isolates were identified as Candida albicans and 61 as non-albicans Candida species. The accuracy of species identification was found to be 71% for Chromagar Candida and 87% for the MALDI-TOF MS system, compared to sequencing. Protease activity was positive in 52% of the isolates, phospholipase in 42%, hemolytic activity in 77%, and biofilm formation in 48%. Kruskal–Wallis analysis revealed no statistically significant interspecies differences in MIC distributions for amphotericin B, fluconazole, itraconazole, or nystatin (p > 0.05), although species-specific trends were observed, with higher fluconazole MICs in C. albicans and lower MIC values in C. tropicalis.  Conclusions: Determining the distribution of Candida species, as well as their virulence factors and antifungal MIC profiles, is of great importance for developing appropriate treatment strategies and reducing related morbidity and mortality. Full article

This review is a comprehensive investigation of avian candidiasis, mainly caused by Candida albicans, although the prevalence of non-albicans Candida species has increased in domestic and wild birds. Avian candidiasis causes significant economic losses in poultry production through increased mortality, cost of treatments, and reduced growth rates, particularly in young birds and intensive farming operations. The pathogenesis section provides a description of the molecular virulence factors such as adhesin-mediated attachment (ALS, Agglutinin-Like Sequence family; HWP1, Hyphal Wall Protein 1), yeast-to-hypha morphogenesis, tissue damage by Candidalysin, biofilm formation on mucosal and abiotic surfaces, and secreted hydrolytic enzymes including secreted aspartyl proteinases (SAPs) and phospholipases. The identified predisposing factors include immunosuppression, malnutrition, abuse of antibiotics, bad husbandry, and crop stasis. The diagnostic methods discussed encompass cytological analysis and fungal culture on selective media to more sophisticated methods of molecular analysis (PCR, MALDI-TOF MS, and NGS). Antifungal susceptibility investigations indicate that nystatin and amphotericin B are still very effective against most avian isolates and that resistance to the azoles is on the rise, especially with respect to the non-albicans Candida species. Nystatin is still the first-line treatment of localized infections; azoles are still used for resistant or systemic infections despite their hepatotoxicity. Sanitation, proper nutrition, and proper use of antimicrobials are essential to prevent diseases. The knowledge gaps comprise the absence of avian-specific pharmacokinetic information, poor knowledge of species-species virulence phenotypes, and the lack of point-of-care diagnostics. The need to have integrated One Health surveillance systems is emphasized by the zoonotic potential of the avian Candida reservoirs. 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

Background: Cutaneous wounds are common in outpatient care, but national patterns of who manages them and how antimicrobials are used remain unclear. Objectives: To characterize outpatient specialty involvement and antimicrobial use for acute and chronic cutaneous wound visits in the United States. Methods: We conducted a retrospective cross-sectional analysis of 2011–2019 National Ambulatory Medical Care Survey (NAMCS) data. Cutaneous wound visits were identified using prespecified ICD-9-CM and ICD-10-CM codes and classified as acute (open or traumatic wounds and burns) or chronic (pressure injuries and lower-limb ulcers). Survey weights were applied to estimate national visit volumes, specialty shares, and antimicrobial utilization patterns. Results: We identified 45.1 million cutaneous wound visits, representing 0.8% of all outpatient visits, of which about two thirds were acute and one third chronic. Primary care physicians accounted for the largest share of wound visits, while dermatologists managed 3.9% of overall wound visits, 2.4% of acute visits, and 7.4% of chronic visits. Among 156.6 million medications recorded at wound visits, antimicrobials represented 13.1% overall, 14.9% in acute visits, and 10.2% in chronic visits. Cephalexin accounted for 32.1% of antimicrobial medications overall and 39.2% in acute visits, whereas chronic wound visits had a more heterogeneous antimicrobial profile that included topical mupirocin, cephalexin, trimethoprim–sulfamethoxazole, and topical nystatin. Conclusions: Outpatient cutaneous wound care in the United States is delivered predominantly by primary care clinicians and relies heavily on a small set of systemic and topical antimicrobials, highlighting opportunities to strengthen antimicrobial stewardship and expand dermatology’s role in chronic wound management. Full article

Saliva is essential for maintaining oral health, and conditions like hyposalivation increase the risk of diseases. To address this, artificial saliva (AS) formulations incorporated with antimicrobials have been proposed. This study aimed to evaluate the antimicrobial activity and determine the minimum inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of AS formulations containing nystatin (Nys), chlorhexidine diacetate 98% (Chx), and silver nanoparticles (AgNp) against Candida albicans biofilm. The fungistatic and fungicidal properties of six groups (AS; AS + AgNp 2 mM; AS + AgNp 4 mM; AS + AgNp 6 mM; AS + Nys; AS + Chx) were assessed using the XTT colorimetric assay. Additionally, 35 denture base heat-polymerized acrylic resin specimens were prepared and treated with the antimicrobials, serving as substrates for C. albicans biofilm development over 3, 6, and 12 h. Biofilm growth was quantified by CFU/mL counting. All analyses were performed with a significance level of p < 0.05. Results demonstrated fungal load inhibition and a reduction in metabolic activity across all experimental groups (p < 0.05). Notably, AS + Nys, AS + Chx, and AS + AgNp 6 mM exhibited similar and significant inhibitory effects against C. albicans biofilm. Full article

Head and neck cancer (HNC) patients frequently experience alterations in the oral environment following radiotherapy, including xerostomia and impaired mucosal integrity, which may favour fungal overgrowth. This study aimed to characterise oral Candida colonisation in radiotherapy-treated HNC patients and compare it with that of healthy individuals. Unstimulated saliva samples from 61 HNC patients and 100 controls were cultured on chromogenic agar, and isolates were identified using API 20C AUX or MALDI-TOF. Salivary flow was measured to quantify xerostomia. A representative subset of isolates (10 per group) underwent antifungal susceptibility testing by disk diffusion according to CLSI/EUCAST criteria. Candida colonisation was significantly higher in HNC patients than in controls (64.6% vs. 20%, p < 0.001), with greater species diversity and increased detection of non-albicans yeasts, including C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei. All HNC patients exhibited reduced salivary flow. Azole resistance was more frequent among HNC isolates (26%) than among controls (10%), whereas all isolates remained susceptible to amphotericin B and nystatin. These findings indicate that radiotherapy-associated xerostomia substantially alters the oral mycobiota and underscore the importance of routine species-level identification and antifungal susceptibility testing in HNC patients to guide clinical decision-making. Full article