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22 pages, 3133 KB  
Article
Anandamide Targets Membrane Integrity in Non-Albicans Candida: A Novel Antifungal Approach
by Goldie Wolfson, Doron Steinberg, Itzhack Polacheck and Maya Korem
J. Fungi 2026, 12(8), 616; https://doi.org/10.3390/jof12080616 - 16 Aug 2026
Abstract
Fungal infections remain a major threat to human health, with non-albicans Candida (NAC) species causing more than half of all clinical cases and many strains gaining resistance to current treatments rapidly. Previously, N-arachidonoyl ethanolamine (anandamide, AEA) has been studied and shown to [...] Read more.
Fungal infections remain a major threat to human health, with non-albicans Candida (NAC) species causing more than half of all clinical cases and many strains gaining resistance to current treatments rapidly. Previously, N-arachidonoyl ethanolamine (anandamide, AEA) has been studied and shown to possess antibacterial and antifungal properties against various bacteria and Candida albicans. Given the previous findings, we aim here to expand the current preliminary research on AEA to investigate its antifungal activities against clinically relevant NAC species in vitro: Candida glabrata, Candida parapsilosis, and Candidaozyma auris. The minimum inhibitory concentration (MIC) and growth curve analysis determined planktonic inhibition. MTT metabolic assay and ATP production via BacTiter-Glo luminescence assay evaluated biofilm formation. Membrane fluidity, polarization and efflux pump activity were examined using fluorescence probes Laurdan, DiS-C3(3), and Rhodamine 6G, respectively. Reactive oxygen species (ROS) were assessed using DCFH-DA. Biofilm architecture and cell viability were analyzed by spinning disk confocal microscopy (SDCM). AEA reduced MIC values and slowed planktonic growth, while MTT and ATP assays demonstrated a pronounced dose-dependent reduction in biofilm metabolic activity. Membrane-targeted effects revealed increased fluidity and permeability at 125 µg/mL. Notably, AEA rapidly impaired efflux pump activity and induced intracellular ROS production. This effect was accompanied by reduced cell viability, increased proportions of PI-positive cells, and enhanced intracellular dye retention, as confirmed by SDCM. Together, these findings demonstrate that AEA exerts antifungal activity by disrupting membrane integrity and associated cellular functions and provide the first comparative characterization of species-specific membrane and oxidative stress responses to AEA across three major clinically relevant multidrug-resistant NAC species. Full article
(This article belongs to the Section Fungal Pathogenesis and Disease Control)
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18 pages, 3050 KB  
Article
RcAlb-PepII Perturbs the Proteomic Profile of Cryptococcus neoformans, Shutting Down Proteins Involved in Fungal Survival
by Nicholas Silva dos Santos Filho, Lua Silva, Rossana de Aguiar Cordeiro, Patrícia Gomes Lima, Nilton Araripe dos Santos Neto, Pedro Victor da Rocha Lima, Francisco Italo Rodrigues Gomes, João Lucas Timbó Mororó, José Hélio de Araújo Filho, Felipe Pantoja Mesquita and Pedro Filho Noronha Souza
Microorganisms 2026, 14(8), 1800; https://doi.org/10.3390/microorganisms14081800 - 15 Aug 2026
Viewed by 29
Abstract
Antimicrobial peptides (AMPs) occur naturally in living organisms and play an essential role in defense against pathogens. Consequently, these peptides are significant in public health research as alternatives in addressing microbial resistance. Here, we present the proteomic profile of Cryptococcus neoformans treated with [...] Read more.
Antimicrobial peptides (AMPs) occur naturally in living organisms and play an essential role in defense against pathogens. Consequently, these peptides are significant in public health research as alternatives in addressing microbial resistance. Here, we present the proteomic profile of Cryptococcus neoformans treated with RcAlb-PepII, an AMP derived from the 2S albumin of Ricinus communis seed cake. This research is noteworthy, as C. neoformans is an emerging fungal pathogen classified by the World Health Organization (WHO) as a critical threat. Proteomic analysis revealed depletion of proteins involved in DNA and RNA metabolism, reduced protein biosynthesis, and mitochondrial damage-associated proteins in C. neoformans following RcAlb-PepII treatment. These findings advance the understanding of the therapeutic profile of AMPs and underscore their importance in combating critical pathogens. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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26 pages, 12863 KB  
Article
Exploring the Molecular Mechanism of Cinnamaldehyde Intervening in Ochratoxin A-Induced Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Comorbidity: An Integrated Approach Based on Network Pharmacology, Network Toxicology and Molecular Docking
by Mingli Shen, Qingping Shi, Shuang Gao, Beiyan Chen and Jieru Han
Pharmaceuticals 2026, 19(8), 1283; https://doi.org/10.3390/ph19081283 - 13 Aug 2026
Viewed by 152
Abstract
Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it [...] Read more.
Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article
(This article belongs to the Special Issue Network Pharmacology of Natural Products, 3rd Edition)
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41 pages, 2097 KB  
Systematic Review
Active Screening for C. auris Colonisation: A Preventive Step or an Excessive Measure? A Systematic Review
by Margarida Alves, Elisabete Ricardo and Sofia Costa de Oliveira
J. Fungi 2026, 12(8), 603; https://doi.org/10.3390/jof12080603 - 13 Aug 2026
Viewed by 241
Abstract
Background: Patients’ and surfaces’ colonisation play a pivotal role in C. auris transmission. Understanding how, when, and where screening for colonisation should be done is important to control the spread. Methods: This systematic review searched studies regarding C. auris patient colonisation, without previous [...] Read more.
Background: Patients’ and surfaces’ colonisation play a pivotal role in C. auris transmission. Understanding how, when, and where screening for colonisation should be done is important to control the spread. Methods: This systematic review searched studies regarding C. auris patient colonisation, without previous outbreaks, until October 2024. Patient demographic and clinical data, sample type, collecting procedure, laboratory methods for strain identification, Clade determination, and susceptibility profile were collected. Results: Thirty-eight studies published between 2019 and 2023 across 18 countries were included using well-established inclusion criteria. Various body sites were screened mainly in patients admitted to intensive care units (ICUs). Patients had various comorbidities and were more commonly colonised during hospitalisation, compared to admission. Most of the isolates belonged to Clade I. Of 19 studies determining antifungal susceptibility, 15 reported resistance, mainly to azoles. Azole resistance was consistently associated with ERG11 substitutions (Y132F/K143R in Clade I, and V125A/F126L in Clade III). Conclusions: Healthcare workers should be on high alert for older, long-term hospitalised, ICU patients with comorbidities and co-colonisation with other pathogens. Composite bilateral axilla-groin sampling should remain the standard minimum approach. Additional anatomical sites may be considered. Well-equipped laboratories are vital for precision identification and antifungal susceptibility testing. Full article
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14 pages, 281 KB  
Article
Phytochemical Screening and Antimicrobial Activity Evaluation of Armenian Chaerophyllum bulbosum L.
by Neli Ghukasyan, Naira Shaboyan, Elena Arutinian, Arshaluys Ghazaryan, Vahe Hovhannisyan, Gayane Poghosyan, Marine Hovhannisyan, Kostandin Manukyan, Greta Ulikhanyan, Sona Feschyan, Maya Hovsepyan, Lusine Danielyan, Hrachya Hovhannisyan, Naira Chichoyan and Serkos Haroutounian
Molecules 2026, 31(16), 2806; https://doi.org/10.3390/molecules31162806 - 12 Aug 2026
Viewed by 179
Abstract
This study is the first report on the chemical composition and antimicrobial activity of Chaerophyllum bulbosum L. sampled from the Armenian flora. Essential oil (EO) and hydrosol were obtained from the aerial parts by hydrodistillation, and their chemical compositions were determined by GC–MS, [...] Read more.
This study is the first report on the chemical composition and antimicrobial activity of Chaerophyllum bulbosum L. sampled from the Armenian flora. Essential oil (EO) and hydrosol were obtained from the aerial parts by hydrodistillation, and their chemical compositions were determined by GC–MS, identifying a total of 48 volatiles. The EO was composed of 60.42% monoterpenes and their oxygenated derivatives and 18.75% sesquiterpenes and their oxygenated derivatives, while the hydrosol was composed of 75% oxygenated monoterpenes, with the remaining 20% and 5% being monoterpenes and sesquiterpenoids respectively. Pulegone (21.55%) was identified as the major constituent. With regard to the non-volatile fraction, the methanolic extract displayed a total phenolic content of 1.17 ± 0.03 mg GAE/g dry weight and a total flavonoid content of 0.62 ± 0.02 mg QE/g, as well as significant antioxidant capacity, with IC50 values of 2.87 ± 0.06 μg Trolox/g dried plant sample for the DPPH assay and 46.87 ± 1.2 μmol Fe2+/g dried plant sample for the FRAP assay. The evaluation of EO and hydrosol antimicrobial properties revealed notable antibacterial activity against Gram-positive bacteria, with inhibition zones ranging from 13.5 to 20 mm. The respective minimum inhibitory concentration (MIC) values ranged from 0.4 to 6.0 mg/mL for the EO and from 62.5 to 400 μL/mL for hydrosol, while the minimum bactericidal concentration (MBC) values ranged from 0.8 to 10.0 mg/mL and from 125 to 800 μL/mL, respectively. Streptococcus mutans was the most susceptible microorganism (MIC = 0.4 mg/mL), whereas Pseudomonas aeruginosa was the most resistant (MIC = 6.0 mg/mL). Both the EO and hydrosol exhibited antifungal activity against Candida albicans, with inhibition zones of 13.0 ± 1.2 mm and 11.0 ± 0.8 mm, respectively. The MIC and MBC values were 1.0 and 2.0 mg/mL for the EO, while the respective values for the hydrosol were 400 and 800 μL/mL. These findings highlight the C. bulbosum plant as a promising source of bioactive compounds with significant activity against Gram-positive bacteria and moderate antifungal effects that may be associated with the high content of pulegone, a monoterpene known for its membrane-disruptive properties. Full article
59 pages, 3297 KB  
Review
Therapeutic Failure in Invasive Fungal Infections: Beyond Antifungal Resistance—A Narrative Review
by Pilar Rivas-Pinedo and José Millán Oñate Gutiérrez
J. Fungi 2026, 12(8), 596; https://doi.org/10.3390/jof12080596 - 11 Aug 2026
Viewed by 307
Abstract
Invasive fungal infections (IFIs) are associated with high morbidity and mortality, particularly in immunocompromised or critically ill patients and in those with complex comorbidities. Despite advances in mycological diagnosis and antifungal therapy, outcomes remain poor in a significant proportion of patients. In clinical [...] Read more.
Invasive fungal infections (IFIs) are associated with high morbidity and mortality, particularly in immunocompromised or critically ill patients and in those with complex comorbidities. Despite advances in mycological diagnosis and antifungal therapy, outcomes remain poor in a significant proportion of patients. In clinical practice, a poor response is often attributed to microbiological resistance. This interpretation may lead to empirical treatment escalation, combination therapy without a clear indication, increased toxicity, clinically relevant drug–drug interactions, and inefficient use of healthcare resources. However, therapeutic failure rarely results from a single mechanism. More often, it reflects the interaction among host vulnerability, pathogen characteristics, delayed, incomplete, or incorrect diagnosis, insufficient antifungal exposure, and inadequate source control. This narrative review presents a structured clinical approach to evaluating suboptimal responses in IFIs without attributing them solely to antifungal resistance. It examines cross-cutting determinants and specific patterns associated with invasive aspergillosis, invasive candidiasis and persistent candidemia, cryptococcal meningitis, mucormycosis, infections caused by rare filamentous fungi, and disseminated endemic mycoses. It also presents clinical algorithms, checklists, and potential quality indicators to distinguish true from apparent failure, identify modifiable factors, and support transparent clinical decision-making within antifungal stewardship programs. The proposed framework supports the assessment of non-response through systematic diagnostic and therapeutic reassessment, timely source control, and identification of modifiable gaps in care. Full article
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34 pages, 4075 KB  
Article
Linker Engineering of Hybrid Triazole-Thiazolidine Antifungals Identifies a Promising Lead Against Drug-Resistant Candida Species
by Alexander Yu. Rudenko, Olga A. Komarova, Alexander Yu. Simonov, Ratislav M. Ozhiganov, Dmitrii A. Averianov, Sofiia R. Kuklich, Ekaterina A. Guseva, Sofya Y. Sokolskaya, Lyudmila G. Kuz’mina, Natalia E. Grammatikova, Alexander B. Kulko, Victoria A. Bidiuk, Sofia S. Mariasina, Vasiliy A. Ivlev, Peter V. Sergiev, Vladimir I. Polshakov, Alexey B. Mantsyzov and Igor B. Levshin
Pharmaceuticals 2026, 19(8), 1260; https://doi.org/10.3390/ph19081260 - 10 Aug 2026
Viewed by 242
Abstract
Background: The emergence of antifungal resistance and the limited number of clinically available antifungal drug classes necessitate the development of new agents with improved efficacy and safety. We investigated how linker architecture influences the antifungal activity and lead properties of hybrid triazole-thiazolidine derivatives. [...] Read more.
Background: The emergence of antifungal resistance and the limited number of clinically available antifungal drug classes necessitate the development of new agents with improved efficacy and safety. We investigated how linker architecture influences the antifungal activity and lead properties of hybrid triazole-thiazolidine derivatives. Methods: A focused library of triazole-thiazolidine hybrids incorporating alkylamine, amide, cyclic amine, 2-hydroxypropyl, and thiazepane linkers was synthesized and characterized. Antifungal activity was evaluated against reference strains and clinical isolates of Candida spp., Aspergillus fumigatus, dermatophytes, and Cryptococcus neoformans. Structure–activity relationships were analyzed by molecular docking. Selected compounds were further assessed by SCRAPPY profiling, fluorescence microscopy, mammalian-cell cytotoxicity assays, acute oral toxicity studies, and evaluation of microsomal stability and interactions with human CYP450 isoforms. Results: Linker architecture strongly influenced antifungal potency. Amide- and cyclic amine-containing hybrids were generally the most active, whereas simple alkylamide derivatives showed narrower activity profiles. Compound 28 emerged as the most promising lead, exhibiting sub-microgram MIC values against several Candida isolates, particularly C. parapsilosis, and retaining measurable activity against an azole-resistant C. albicans strain. Docking generated putative CYP51-binding models, while SCRAPPY profiling and fluorescence microscopy revealed an azole-like cellular response consistent with perturbation of sterol-associated homeostasis. Compound 28 was tolerated at 300 mg/kg in an acute oral study but showed concentration- and time-dependent cytotoxicity and rapid CYP3A4-mediated microsomal metabolism. Conclusions: Systematic variation of linker architecture identified compound 28 as a promising exploratory antifungal lead. Further optimization should focus on improving metabolic stability and cytotoxicity, together with direct target validation, pharmacokinetic characterization, and in vivo efficacy studies. Full article
(This article belongs to the Section Medicinal Chemistry)
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21 pages, 3113 KB  
Article
Essential Oils as Potential Alternatives to Synthetic Fungicides for the Control of Two Fusarium Head Blight Pathogens
by Renata Žvirdauskienė, Renata Baranauskienė, Dalia Čižeikienė, Daiva Žadeikė and Simona Paulikienė
Appl. Sci. 2026, 16(16), 7959; https://doi.org/10.3390/app16167959 - 10 Aug 2026
Viewed by 250
Abstract
Fusarium head blight of cereal, caused by fungi of the genus Fusarium spp., reduces yield and accumulates mycotoxins. The increasing resistance of pathogens to synthetic fungicides encourages the search for natural alternatives. This work aims to determine the chemical composition of essential oils [...] Read more.
Fusarium head blight of cereal, caused by fungi of the genus Fusarium spp., reduces yield and accumulates mycotoxins. The increasing resistance of pathogens to synthetic fungicides encourages the search for natural alternatives. This work aims to determine the chemical composition of essential oils (EOs) of caraway, sage, and pine and to evaluate their antifungal activity against Fusarium graminearum and Fusarium culmorum. The composition of EOs was determined by gas chromatography and gas chromatography–mass spectrometry, and activity was assessed by agar dilution to determine mycelial growth inhibition and EC50, with the effect evaluated by two-way ANOVA. Caraway EO, belonging to the carvone chemotype (carvone 57.57%, limonene 35.86%), had the highest antifungal activity (EC50 = 727 ppm), sage EO (cis-thujone 29.59%, camphor 21.74%) had an average activity (EC50 = 1017 ppm), and pine EO, rich in α-pinene and δ-3-carene, had the lowest activity (EC50 > 3000 ppm). The antifungal activity was determined by the compounds’ chemical nature, not by their amount. Low EO concentrations (125–250 ppm) elicited a biphasic response, promoting mycelial growth (zero effect point ≈ 269–295 ppm); therefore, insufficient dosage could increase the risk of mycotoxin contamination. Carvone-rich caraway EO exhibited the highest antifungal activity among the oils tested and is worthy of further investigation as a potential tool for sustainable control of Fusarium head blight in cereals. Full article
(This article belongs to the Special Issue Advances in Food Safety and Microbial Control, 2nd Edition)
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24 pages, 3387 KB  
Article
Antimicrobial Photodynamic Inactivation Using Riboflavin 5′-Phosphate and a 450 nm Diode Laser: An In Vitro Dose-Optimisation Study
by Maciej Łopaciński, Anna Mertas, Anna Kuśka-Kiełbratowska, Elżbieta Bobela, Eleftherios Terry R. Farmakis, Dariusz Skaba and Rafał Wiench
Pharmaceutics 2026, 18(8), 977; https://doi.org/10.3390/pharmaceutics18080977 - 8 Aug 2026
Viewed by 194
Abstract
Background: Rising antifungal and antibiotic resistance among Candida species, Staphylococcus aureus, and Enterococcus faecalis has renewed interest in antimicrobial photodynamic therapy (aPDT) as a resistance-independent strategy. Riboflavin 5′-phosphate is a biocompatible, blue-light-activated photosensitizer, but standardized dosing across fungal and bacterial targets [...] Read more.
Background: Rising antifungal and antibiotic resistance among Candida species, Staphylococcus aureus, and Enterococcus faecalis has renewed interest in antimicrobial photodynamic therapy (aPDT) as a resistance-independent strategy. Riboflavin 5′-phosphate is a biocompatible, blue-light-activated photosensitizer, but standardized dosing across fungal and bacterial targets is lacking. Objective: The aim of this study was to systematically optimize pre-irradiation incubation time, photosensitizer volume, irradiation time, and laser power for riboflavin 5′-phosphate aPDT (450 nm diode laser) against C. albicans, C. glabrata, C. krusei, S. aureus, and E. faecalis, and compare species susceptibility under optimized conditions. Methods: ATCC strains were treated with 0.1% riboflavin 5′-phosphate across four groups (photodynamic, photosensitizer-only, laser-only, control) in a staged design optimizing incubation (1–30 min), photosensitizer volume (50–150 µL), irradiation time (10–120 s), and power (50–400 mW). Viable counts (CFU/mL) were quantified. Results: Significant reductions occurred only with combined light-plus-photosensitizer treatment. Optimal parameters were 15 min incubation, 100 µL photosensitizer for Candida spp. (50 µL for bacteria), and 120 s at 400 mW, though C. albicans and C. krusei plateaued by 60 s. Maximum reductions were modest: 53.5% (C. albicans), 46.7% (S. aureus), 37.9% (C. glabrata), 35.9% (C. krusei), and 26.5% (E. faecalis), all below 1 log10. A significant light × photosensitizer interaction, confirming photodynamic specificity, was seen for C. albicans, C. glabrata, and S. aureus, but not C. krusei or E. faecalis. Conclusions: Riboflavin 5′-phosphate aPDT under 450 nm light produces reproducible, dose-dependent, species-specific antimicrobial activity, best suited as an adjunctive rather than stand-alone therapy pending biofilm and in vivo validation. Full article
(This article belongs to the Section Clinical Pharmaceutics)
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10 pages, 243 KB  
Review
Candida Infections: Epidemiology, Clinical Manifestations and Quality-of-Life Burden
by Ana R. Miljković
Microbiol. Res. 2026, 17(8), 154; https://doi.org/10.3390/microbiolres17080154 - 7 Aug 2026
Viewed by 299
Abstract
Candida infections represent a major global public health challenge and remain among the most common opportunistic fungal infections worldwide. Although Candida albicans remains the predominant pathogen, the incidence of infections caused by non-albicans species, particularly Candidozyma auris, has increased substantially in recent [...] Read more.
Candida infections represent a major global public health challenge and remain among the most common opportunistic fungal infections worldwide. Although Candida albicans remains the predominant pathogen, the incidence of infections caused by non-albicans species, particularly Candidozyma auris, has increased substantially in recent years. Candida infections range from superficial mucocutaneous disease to invasive life-threatening infections associated with high morbidity and mortality. In addition to clinical burden, growing evidence indicates a substantial negative impact on health-related quality of life, particularly among patients with recurrent vulvovaginal candidiasis and chronic fungal infections. Full article
14 pages, 646 KB  
Article
Antifungal Susceptibility and Cyp51A Gene Variation Analysis of Aspergillus fumigatus Isolated from Soils in Tea-Growing Areas of Guizhou, China
by Duanyong Zhou, Yixian Liu, Mingyue Wang, Cai Yang, Ying Zhang and Jianping Xu
Microorganisms 2026, 14(8), 1704; https://doi.org/10.3390/microorganisms14081704 - 4 Aug 2026
Viewed by 256
Abstract
Aspergillus fumigatus is the predominant pathogenic fungus responsible for aspergillosis. In recent years, the global detection rate of azole-resistant A. fumigatus has continuously increased, and the extensive application of agricultural azole fungicides has been recognized as a crucial driving factor for the emergence [...] Read more.
Aspergillus fumigatus is the predominant pathogenic fungus responsible for aspergillosis. In recent years, the global detection rate of azole-resistant A. fumigatus has continuously increased, and the extensive application of agricultural azole fungicides has been recognized as a crucial driving factor for the emergence and spread of resistance mutations in environmental A. fumigatus. Previous investigations conducted by our research team in karst vegetable fields of Guizhou Province revealed that the triazole resistance rate of local A. fumigatus was only 0.49%, which was markedly lower than those reported in most previous studies in China and outside of China. To supplement the prevalence data of azole resistance across different habitats in this region, a total of 191 environmental A. fumigatus strains were isolated from nine tea plantations across Guizhou. In this study, two clinically prevalent azole drugs, itraconazole and voriconazole, were used for antifungal susceptibility testing, and the triazole target gene cyp51A of all isolates was sequenced and analyzed. Antifungal susceptibility results demonstrated that the MIC ranges of the tea plantation A. fumigatus population were 0.015–0.5 μg/mL for itraconazole and 0.031–0.25 μg/mL for voriconazole, with no evidence of triazole resistance. Genetic analysis identified ten different gene mutations among 29 isolates, all of which were classified as non-resistance-associated mutations. Among these mutations, four were synonymous mutations, including 267G→A, 540G→A, 1074A→G, and 1362T→C, while six were non-synonymous mutations, including 137T→A, 514A→G, 743A→C, 744T→A, 765C→G, and 1279G→A. These non-synonymous mutations resulted in five amino acid substitutions in 25 strains, namely F46Y, M172V, N248T/K, D255E, and E427K. The N248T/K mutation exhibited the highest mutational frequency of 0.1309 (25/191) and was distributed across all nine sampling sites. Correlation analyses indicated that no significant correlations were observed between all detected variant loci and MICs of isolates to itraconazole and voriconazole. Phylogenetic analysis revealed that the six sequence types of cyp51A in Guizhou tea plantations were broadly intermixed with those from other parts of China and outside of China. We discussed the implications of these results in the management of antifungal resistance. Full article
(This article belongs to the Special Issue Ecology and Genetics of Medically Important Fungi)
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19 pages, 1863 KB  
Article
Cold Atmospheric Plasma Disrupts Microbial Wound Bioburden: In Vitro, Porcine MRSA Biofilm, and Clinical Fluorescence Evidence from Bench to Bedside
by Steven Jeffery, Ahmad Wakaf, Lennart Marlinghaus, Sören Gatermann, Thomas Meyer, Joel Gil, Ivan Jozic and Stephen C. Davis
Biomedicines 2026, 14(8), 1750; https://doi.org/10.3390/biomedicines14081750 - 3 Aug 2026
Viewed by 387
Abstract
Background: Biofilm-associated microbial burden is a major barrier to wound healing and is increasingly difficult to control in the era of antimicrobial resistance. This translational study evaluated the antimicrobial performance and tissue compatibility of a commercially available large-area cold atmospheric plasma (CAP) system [...] Read more.
Background: Biofilm-associated microbial burden is a major barrier to wound healing and is increasingly difficult to control in the era of antimicrobial resistance. This translational study evaluated the antimicrobial performance and tissue compatibility of a commercially available large-area cold atmospheric plasma (CAP) system (CPTpatch®/CPTcube®; Coldplasmatech GmbH, Greifswald, Germany) across in vitro, porcine, and clinical patient settings. Methods: CAP was tested against seven wound-relevant bacterial species, including multidrug-resistant strains, and the fungus Candida albicans in vitro, in two porcine MRSA-infected deep dermal wound models, and in a clinical service-evaluation cohort of 20 chronic lower-limb wounds in 14 patients; 17 wounds had evaluable longitudinal MolecuLight® (Toronto, ON, Canada) fluorescence series. Results: In vitro, CAP induced rapid multi-log killing across the bacterial panel and showed a marked antifungal effect against C. albicans. In porcine MRSA wounds, CAP reduced bacterial burden versus sham by 1.65, 1.89, and 2.04 log10 CFU/g on Days 4, 8, and 11, equivalent to 97.8%, 98.7%, and 99.1% reductions. In a 72-h post-inoculation MRSA biofilm model, the strongest 5×/week regimen achieved 2.51 log10 (99.69%) and 3.18 log10 (99.93%) reductions versus baseline after 2- and 4-min CAP exposures, respectively. Clinically, twice-weekly CAP was associated with a significant decline in MolecuLight® fluorescence grades over 5 weeks (p < 0.001); effective surface disinfection at 5 weeks was observed in 16/17 evaluable wounds. Conclusions: From bench to bedside, the investigated CAP system delivered rapid broad-spectrum antimicrobial activity, reduced MRSA burden in biofilm-infected porcine wounds, and was associated with clinically measurable suppression of wound surface bioburden while remaining tissue-sparing. These findings support further controlled studies to define clinical benefit in wound care. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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17 pages, 13179 KB  
Article
Antifungal Effects of Plant Extracts on Saffron Corms Infected with Three Pathogens
by Zhihao Xu, Zheren Tong, Hanxiang Huang, Hongyu Xu, Shaoxian Wang, Zhiwen Zhang, Tao Lv, Fujia Luan, Peishi Feng, Jianhong Zhang, Zijin Xu and Ping Wang
Agronomy 2026, 16(15), 1475; https://doi.org/10.3390/agronomy16151475 - 2 Aug 2026
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Abstract
Background: Saffron corm rot causes significant yield losses worldwide. Although synthetic pesticides are commonly used for management, their overuse can lead to increased fungal resistance and pose a risk to public health. Numerous plants possessing antifungal properties hold significant potential for development as [...] Read more.
Background: Saffron corm rot causes significant yield losses worldwide. Although synthetic pesticides are commonly used for management, their overuse can lead to increased fungal resistance and pose a risk to public health. Numerous plants possessing antifungal properties hold significant potential for development as biocontrol agents against saffron corm rot. Result: In this study, the efficacy of biocontrol agents derived from natural plants was evaluated for managing saffron corm rot. Aqueous and 70% ethanol extracts from 15 plants were investigated for antifungal activity and virulence suppression against three saffron pathogens: Fusarium oxysporum, Penicillium citrinum, and Aspergillus brasiliensis. Antifungal activity experiments indicated that clove ethanol extract at a concentration of 20 mg/mL exhibited the highest inhibition rate, with values of 93.27 ± 0.0% for Fusarium oxysporum, 86.47 ± 5.55% for Penicillium citrinum, and 68.65 ± 2.40% for Aspergillus brasiliensis. Compared with the model group, clove ethanol extract significantly reduced corm rot and normalized the metabolism of infected corms. On day 30, compared with the model group (34.3 ± 3.7%), the rot rate of clove-treated corms was reduced to 17.2 ± 1.4%, and on day 60, it was reduced to 27.5 ± 1.5% (versus 52.9 ± 3.3% in the model group). Compared with the model group, the levels of soluble sugar, starch, α-amylase, soluble protein, and superoxide dismutase in clove-treated infected corms approached those observed in the control group. Field trials confirmed that clove ethanol extract effectively improved plant growth and reduced the disease severity index (37.00 ± 3.51) in infected corms. Conclusion: Clove ethanol extract is a promising candidate to replace or reduce the use of synthetic pesticides. It provides a theoretical and practical basis for the biocontrol of saffron corm rot. Full article
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14 pages, 3291 KB  
Article
Integrated Phytochemical Profiling, Spectroscopic Analysis, and Molecular Docking Evaluation of Ethanolic Plant Extracts Against Candida Receptor (1IYK)
by Jacob Mathew Philip, Krishnan Mahalakshmi, Helen Mary Abraham and Leena Sankari Sankar
J. Fungi 2026, 12(8), 573; https://doi.org/10.3390/jof12080573 - 1 Aug 2026
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Abstract
Background: The increasing prevalence of antifungal resistance among Candida albicans isolates necessitates the exploration of alternative antifungal strategies and novel molecular targets. Plant-derived bioactive compounds represent a promising source of antifungal agents; however, their chemical composition and mechanisms of action remain insufficiently characterized. [...] Read more.
Background: The increasing prevalence of antifungal resistance among Candida albicans isolates necessitates the exploration of alternative antifungal strategies and novel molecular targets. Plant-derived bioactive compounds represent a promising source of antifungal agents; however, their chemical composition and mechanisms of action remain insufficiently characterized. Methods: Ethanolic extracts of Azadirachta indica leaves and Ficus benghalensis aerial roots were subjected to qualitative phytochemical screening, gas chromatography–mass spectrometry (GC–MS), and Fourier transform infrared (FTIR) analysis to characterize their bioactive constituents. Molecular docking studies were performed to evaluate the interaction of selected phytochemicals with C. albicans N-myristoyltransferase (PDB ID: 1IYK), a validated antifungal drug target. Results: Phytochemical screening revealed the presence of alkaloids, carbohydrates, and phenolic compounds in both extracts, while saponins were detected only in A. indica. GC–MS analysis demonstrated greater chemical diversity in A. indica, including fatty acids and phenolic derivatives, compared with F. benghalensis, which was dominated by terpenoids and long-chain hydrocarbons. FTIR analysis confirmed functional groups relevant to protein–ligand interactions. Molecular docking showed favorable binding interactions between several A. indica–derived compounds and N-myristoyltransferase, whereas compounds from F. benghalensis did not exhibit detectable binding under the conditions tested. Conclusions: The integrated phytochemical and in silico analyses provide insight into the antifungal potential of A. indica, suggesting possible interactions between identified phytochemicals and the selected drug target protein. This study highlights the value of combining chemical characterization with target-based computational screening in the rational exploration of plant-derived antifungal agents. Full article
(This article belongs to the Section Fungal Pathogenesis and Disease Control)
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25 pages, 42736 KB  
Review
Functionalization and Enhanced Modification of Soy Protein Adhesives: A Review
by Fei Xiao, Jiaquan Liu, Wenhao Li, Jingyi Guo, Qiong Zheng, Yiqiang Wu, Mingjie Guan, Cheng Li and Jiarong She
Forests 2026, 17(8), 908; https://doi.org/10.3390/f17080908 - 1 Aug 2026
Viewed by 203
Abstract
Adhesive technologies have expanded rapidly and are now widely employed across diverse industrial sectors. However, conventional wood adhesives emit substantial amounts of formaldehyde and rely on fossil-derived feedstocks, posing risks to human health and the environment. Developing sustainable, multi-functional bio-based adhesives has therefore [...] Read more.
Adhesive technologies have expanded rapidly and are now widely employed across diverse industrial sectors. However, conventional wood adhesives emit substantial amounts of formaldehyde and rely on fossil-derived feedstocks, posing risks to human health and the environment. Developing sustainable, multi-functional bio-based adhesives has therefore become increasingly important. As a renewable, environmentally friendly, bio-based material, soy protein shows strong potential to replace formaldehyde-based adhesives in plywood. This review summarizes the molecular structure, bonding mechanisms, and recent advances in functional soy protein adhesives. Topics include bonding strength, water resistance, anti-mold and antibacterial performance, flame retardancy, and electromagnetic shielding. The review discusses theoretical foundations and application prospects for green adhesives and outlines opportunities to design and fabricate high-value, multi-functional bio-based composites. Full article
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