Jorge Alvarruiz, Alba Cecilia Ruiz-Gaitán, Marta Dafne Cabanero-Navalon, Javier Pemán, Rosa Blanes-Hernández, Santiago de Cossio, Victor Garcia-Bustos
{"title":"Phenotypic Impact and Multivariable Assessment of Antifungal Susceptibility in <i>Candida auris</i> Survival Using a <i>Galleria mellonella</i> Model.","authors":"Jorge Alvarruiz, Alba Cecilia Ruiz-Gaitán, Marta Dafne Cabanero-Navalon, Javier Pemán, Rosa Blanes-Hernández, Santiago de Cossio, Victor Garcia-Bustos","doi":"10.3390/jof11060406","DOIUrl":"10.3390/jof11060406","url":null,"abstract":"<p><p>The novel pathogen <i>Candida auris</i> has rapidly become a major health threat due to its high virulence, resistance to multiple antifungal agents, and remarkable environmental persistence. This study evaluated the influence of phenotypic traits and antifungal minimum inhibitory concentrations (MICs) on <i>C. auris</i> virulence using a <i>Galleria mellonella</i> infection model. Ten clinical strains, categorized as aggregative or non-aggregative, were analyzed for antifungal susceptibility and survival outcomes. All strains exhibited fluconazole resistance, with variable susceptibilities to other antifungals. Survival analysis revealed that the non-aggregative phenotype was independently associated with reduced survival in <i>G. mellonella</i> (HR = 2.418, <i>p</i> = 0.015), while antifungal MICs and invasive origin were not significant independent predictors of mortality in an elastic net-adjusted multivariable model. Strong correlations were observed between certain antifungal MICs, suggesting potential cross-resistance patterns; however, no independent association with virulence was identified. These results suggest that <i>C. auris</i> possesses not only an enhanced ability to develop antifungal resistance but also the capacity to do so without incurring fitness costs that could attenuate its virulence.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12193718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ozone Treatment Inhibited the Blue Mold Development and Maintained the Main Active Ingredient Content in <i>Radix astragali</i> Infected by <i>Penicillium polonicum</i> Through Activating Reactive Oxygen Species Metabolism.","authors":"Jihui Xi, Qili Liu, Qingru Zhang, Zhiguang Liu, Huali Xue, Yuqin Feng","doi":"10.3390/jof11060402","DOIUrl":"10.3390/jof11060402","url":null,"abstract":"<p><p><i>Radix astragali</i> is a homologous plant of medicine and food with a variety of health benefits. However, our previous study showed that blue mold, caused by <i>Penicillium polonicum</i>, is the most important postharvest disease of fresh <i>R. astragali</i> during storage. Ozone, as a strong oxidizing agent, can effectively control the occurrence of postharvest diseases in fruits and vegetables. Nevertheless, there are few research studies on the effect of ozone-treated fresh Chinese traditional medicine. In this study, we investigated the effect of ozone gas on the postharvest blue mold development, mycotoxin accumulation, and main active component contents in fresh <i>R. astragali</i> infected by <i>P. polonicum</i>, and analyzed the possible action mechanism on ROS metabolism. The result indicates that ozone application significantly inhibited the development of postharvest blue mold caused by <i>P. polonicum</i> infection, reduced the disease incidence, disease index, and weight loss rate, maintained the main active ingredients in fresh <i>R. astragali</i> by activating ROS metabolism, enhanced the antioxidant enzymatic activity, thus avoiding oxidative damage caused by excessive ROS accumulation, and maintained the integrity of the cell membrane, ultimately controlling the occurrence of blue mold of <i>R. astragali</i>. Moreover, ozone treatment also maintained the contents of the main active ingredients in <i>R. astragali</i> before 14 d during <i>P. polonicum</i> infection. In addition, the amount of active ingredients of astragaloside I, calycosin-7-glucoside, and ononin in the ozone-treated group was higher than that in the control group during the storage period. We speculate that, under the action of ozone, astragaloside IV was converted into astragaloside II by oxidative modification and astragaloside II was further oxidized to astragaloside I, resulting in the accumulation of astragaloside I. Similarity, the hydrogen atoms (-H) on the benzene ring in formononetin were oxidized to phenolic hydroxyl groups (-OH) to generate calycosin, which was further converted into calycosin-7-glucoside, resulting in calycosin-7-glucoside accumulation. This study will provide the theoretical basis for ozone commercial application to control the occurrence of postharvest diseases of <i>R. astragali</i>.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhengfei Cao, Tao Wang, Hui He, Yuling Li, Xiuzhang Li
{"title":"Multiomics Provides a New Understanding of the Effect of Temperature Change on the Fermentation Quality of <i>Ophiocordyceps sinensis</i>.","authors":"Zhengfei Cao, Tao Wang, Hui He, Yuling Li, Xiuzhang Li","doi":"10.3390/jof11060403","DOIUrl":"10.3390/jof11060403","url":null,"abstract":"<p><p><i>Ophiocordyceps sinensis</i> is a medicinal fungus with significant nutritional and utilization value. Temperature is a crucial factor influencing its growth, as temperature changes can impact enzyme activity, metabolite content, and gene expression during fungal cultivation. Currently, there are limited reports on the effects of temperature on the quality of fungal fermentation. This study focuses on <i>O. sinensis</i> and conducts temperature stress culture experiments. The results indicate that the optimal culture temperature range is between 18 and 23 °C, with extreme temperatures negatively affecting the morphology, growth rate, sporulation, and antioxidant systems of the strains. Further metabolomic and transcriptomic analyses revealed that differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were primarily enriched in four metabolic pathways: linoleic acid metabolism, arginine and proline metabolism, and lysine degradation. Many significantly enriched metabolites across various pathways appear to be predominantly regulated by ribosomal and RNA polymerase genes. Furthermore, we cultured <i>O. sinensis</i> mycelium at various temperatures and observed that a significant number of genes and metabolites associated with apoptosis and senescence were expressed at 28 °C. This led to cell damage, excessive energy consumption, and ultimately inhibited mycelial growth. In summary, this study elucidates the response mechanisms of <i>O. sinensis</i> to key metabolic pathways under different temperature growth conditions and explores factors contributing to strain degradation.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ping Lu, Jiaqi Wang, Xiaoli Wang, Dan Wang, Haojie Shi
{"title":"Up-Frameshift Factors from Phytopathogenic Fungi Play a Crucial Role in Nonsense-Mediated mRNA Decay.","authors":"Ping Lu, Jiaqi Wang, Xiaoli Wang, Dan Wang, Haojie Shi","doi":"10.3390/jof11060404","DOIUrl":"10.3390/jof11060404","url":null,"abstract":"<p><p>The nonsense-mediated mRNA decay (NMD) is extensively involved in physiological, pathological, and stress response processes in humans and plants. However, the NMD in phytopathogenic fungi has not yet been thoroughly investigated. In this study, we identified and performed domain analysis on the core components of the NMD in ten globally widespread phytopathogenic fungi that cause significant economic losses. The core components of NMD in these fungi exhibit high similarity to their homologous genes in humans, while also possessing certain specificities. The core factors of the NMD, including the Up-frameshift factors (UPFs) and the exon junction complex (EJC), are generally conserved among phytopathogenic fungi. Notably, suppressors with morphological effects on genitalia (SMG) genes are absent in these fungi, which bears some similarity to the EJC-independent NMD degradation mechanism observed in <i>Saccharomyces cerevisiae</i>. Interestingly, plant pathogenic fungi contain highly homologous genes of the EJC complex, suggesting the presence of an EJC-dependent NMD degradation mechanism. In summary, our findings demonstrate that NMD are prevalent in plant pathogenic fungi, providing a research foundation for subsequent studies on NMD in their growth, development, and involvement in pathogenic processes.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jialiang Pan, Zhijun Yu, Wenhao Dai, Chunhe Lv, Yifan Chen, Hong Sun, Jie Chen, Junxin Gao
{"title":"Genomic Insights into <i>Neofusicoccum laricinum</i>: The Pathogen Behind Chinese Larch Shoot Blight.","authors":"Jialiang Pan, Zhijun Yu, Wenhao Dai, Chunhe Lv, Yifan Chen, Hong Sun, Jie Chen, Junxin Gao","doi":"10.3390/jof11050399","DOIUrl":"10.3390/jof11050399","url":null,"abstract":"<p><p>Larch shoot blight, caused by the fungus <i>Neofusicoccum laricinum</i>, threatens larch (<i>Larix</i> spp.) forests across northeastern China, jeopardizing both timber productivity and ecological stability. This study aimed to investigate the genomic diversity, population structure, and potential adaptive mechanisms of <i>N. laricinum</i> across contrasting climatic regions. To achieve this, we conducted whole-genome resequencing of 23 <i>N. laricinum</i> isolates collected from three major provinces-Heilongjiang, Inner Mongolia, and Jilin-that represent distinct climatic zones ranging from cold-temperate to relatively warmer regions. We identified ~219.1 K genetic variants, offering a detailed portrait of the pathogen's genomic diversity. Population structure analyses, including principal component analysis and phylogenetic tree, revealed clear genetic differentiation aligning with geographic origin and climate. Functional annotation (GO and KEGG) highlighted enrichment in metabolic, stress-response, and membrane transport pathways, suggesting potential adaptation to varied temperature regimes and environmental pressures. Moreover, region-specific variants-particularly missense and stop-gain mutations-were linked to genes involved in ATP binding, oxidoreductase activity, and cell division, underscoring the fungus's capacity for rapid adaptation. Collectively, these findings fill a critical gap in the population genetics of <i>N. laricinum</i> and lay a foundation for future disease management strategies to larch shoot blight under changing climatic conditions.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabiana Dellai, Alberto Pagotto, Francesco Sbrana, Andrea Ripoli, Giacomo Danieli, Alberto Colombo, Denise D'Elia, Monica Geminiani, Simone Giuliano, Assunta Sartor, Carlo Tascini
{"title":"The Impact of Epidemiological Trends and Guideline Adherence on Candidemia-Associated Mortality: A 14-Year Study in Northeastern Italy.","authors":"Fabiana Dellai, Alberto Pagotto, Francesco Sbrana, Andrea Ripoli, Giacomo Danieli, Alberto Colombo, Denise D'Elia, Monica Geminiani, Simone Giuliano, Assunta Sartor, Carlo Tascini","doi":"10.3390/jof11050400","DOIUrl":"10.3390/jof11050400","url":null,"abstract":"<p><p>Invasive candidiasis represents a major global health concern, with incidence and mortality rates expected to rise due to medical advancements and unavoidable risk factors. This retrospective, multicentric study was conducted in eight hospitals in a northeastern Italian region, enrolling adult patients diagnosed with candidemia from 1 January 2018 to 31 December 2022. Epidemiological trends and clinical characteristics were analyzed and compared to those from a prior regional study (2009-2011), allowing a fourteen-year comparative evaluation. A shift in species distribution was observed, with a decline in <i>Candida albicans</i> (from 65.7% to 57.8%) and a rise in non-<i>albicans</i> species, particularly the <i>Candida parapsilosis</i> complex (from 16.1% to 18.2%). Guideline adherence was assessed applying the EQUAL <i>Candida</i> score; scores ≥ than 11.5 were independently associated with improved in-hospital survival (HR 3.51, <i>p</i> < 0.001). Among individual score components, empiric echinocandin therapy and central venous catheter removal correlated with better outcomes. Centers with routine infectious disease (ID) consultations showed higher survival and adherence, reinforcing the value of specialist involvement. These findings support local epidemiological and management practice surveillance program adoption to address context-specific gaps, promote the adoption of best practices in <i>Candida</i> BSI management-as expanded ID specialist consultations and education programs-and, ultimately, reduce candidemia-related mortality rates.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caroline Danner, Yuriy Karpenko, Robert L Mach, Astrid R Mach-Aigner
{"title":"<i>Act1</i> out of Action: Identifying Reliable Reference Genes in <i>Trichoderma reesei</i> for Gene Expression Analysis.","authors":"Caroline Danner, Yuriy Karpenko, Robert L Mach, Astrid R Mach-Aigner","doi":"10.3390/jof11050396","DOIUrl":"10.3390/jof11050396","url":null,"abstract":"<p><p><i>Trichoderma reesei</i> is a well-established industrial enzyme producer and has been the subject of extensive research for various applications. The basis of many research studies is the analysis of gene expression, specifically with RT-qPCR, which requires stable reference genes for normalization to yield reliable results. Yet the commonly used reference genes, <i>act1</i> and <i>sar1</i>, were initially chosen based on reports from the literature rather than systematic validation, raising concerns about their stability. Thus, properly evaluated reference genes for <i>T. reesei</i> are lacking. In this study, five potentially new reference genes were identified by analyzing publicly available transcriptome datasets of the <i>T. reesei</i> strains QM6a and Rut-C30. Their expression stability was then evaluated under relevant cultivation conditions using RT-qPCR and analyzed with RefFinder. The two most stable candidate reference genes were further validated by normalizing the expression of the well-characterized gene <i>cbh1</i> and comparing the results to those obtained using <i>act1</i> and <i>sar1</i>. Additionally, <i>act1</i> and <i>sar1</i> were normalized against the new reference genes to assess the variability in their expression. All five new reference genes exhibited a more stable expression than <i>act1</i> and <i>sar1</i>. Both in silico and RT-qPCR analysis ranked the so far uncharacterized gene, <i>bzp1</i>, as the most stable. Further, we found that <i>act1</i> and <i>sar1</i> have strain- and condition-dependent expression variability, suggesting that they are unsuitable as universal reference genes in <i>T. reesei</i>. Based on these results, we propose to use the combination of <i>bzp1</i> and <i>tpc1</i> for the normalization in RT-qPCR analysis instead of <i>act1</i> and <i>sar1</i>.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Whole-Genome Sequencing and Comparative Genomic Analysis of Three Clinical Bloodstream Infection Isolates of <i>Trichosporon austroamericanum</i>.","authors":"Takanori Horiguchi, Takashi Umeyama, Hiroko Tomuro, Amato Otani, Takayuki Shinohara, Masahiro Abe, Shogo Takatsuka, Ken Miyazawa, Minoru Nagi, Yasunori Muraosa, Yasutaka Hoshino, Takashi Sakoh, Hideki Araoka, Naoyuki Uchida, Tomoyoshi Kaneko, Yuko Nagano, Hiroki Tsukada, Taiga Miyazaki, Yoshitsugu Miyazaki","doi":"10.3390/jof11050401","DOIUrl":"10.3390/jof11050401","url":null,"abstract":"<p><p><i>Trichosporon austroamericanum</i> is a recently described yeast species related to <i>Trichosporon inkin</i> and exclusively isolated from clinical specimens. However, its genomic features and pathogenic potential remain poorly understood. In this study, we performed whole-genome sequencing on three blood-derived isolates from patients with invasive fungal infections and comparative analyses with 13 related <i>Trichosporon</i> species. The three isolates yielded high-quality assemblies of 9-10 scaffolds (~21 Mb), facilitating reliable comparisons. While most species had comparable genome sizes, <i>Trichosporon ovoides</i>, <i>Trichosporon coremiiforme</i>, and <i>Cutaneotrichosporon mucoides</i> displayed large, fragmented genomes, suggestive of polyploidy. ANI analysis and phylogenetic trees based on ANI and single-copy orthologs supported the classification of <i>T. austroamericanum</i> as a distinct clade with moderate intraspecific divergence. Using the <i>Galleria mellonella</i>, a model for fungal pathogenicity, all <i>T. austroamericanum</i> strains reduced larval survival, and NIIDF 0077300 exhibited virulence comparable to <i>T. asahii</i> and greater than <i>T. inkin</i>. To explore the gene-level differences associated with pathogenicity, we performed ortholog analysis based on single-copy genes. This revealed a unique Zn(II)<sub>2</sub>Cys<sub>6</sub>-type transcription factor gene (OG0010545) present only in NIIDF 0077300 and <i>T. asahii</i>. These findings highlight the genomic diversity and infection-associated traits of <i>T. austroamericanum</i>, providing a framework for future functional studies.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhigang Hao, Lei Pan, Jiaqing Xu, Chengxuan Yu, Jianqiang Li, Laixin Luo
{"title":"FGSE02, a Novel Secreted Protein in <i>Fusarium graminearum</i> FG-12, Leads to Cell Death in Plant Tissues and Modulates Fungal Virulence.","authors":"Zhigang Hao, Lei Pan, Jiaqing Xu, Chengxuan Yu, Jianqiang Li, Laixin Luo","doi":"10.3390/jof11050397","DOIUrl":"10.3390/jof11050397","url":null,"abstract":"<p><p>Fungal phytopathogens employ effector proteins and secondary metabolites to subvert host immunity. Effector proteins have attracted widespread interest in infection, especially for unknown, unreported genes. However, the type of protein remains much less explored. Here, we combined transcriptome analysis and functional validation to identify virulence-associated genes in <i>Fusarium graminearum</i> during fungi infection. A unique secreted protein, FGSE02, was significantly upregulated in the early infection stage. Proteomic characterization revealed that the protein contains a functional signal peptide but lacks known domains. The transient expression of FGSE02 in <i>Nicotiana benthamiana</i> induced rapid cell death, while gene knockout stains reduced fungal virulence without affecting growth. Our findings highlight FGSE02 as a key virulence factor, offering potential targets for disease control. Taken together, the results of this study identify a pathogenic factor and provide new insights into the development of green pesticides.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myricetin Exerts Antibiofilm Effects on <i>Candida albicans</i> by Targeting the RAS1/cAMP/EFG1 Pathway and Disruption of the Hyphal Network.","authors":"Melda Meral Ocal, Merve Aydin, Esra Sumlu, Emine Nedime Korucu, Ali Ozturk","doi":"10.3390/jof11050398","DOIUrl":"10.3390/jof11050398","url":null,"abstract":"<p><p>Increasing antifungal resistance and side effects of existing drugs demand alternative approaches for treating <i>Candida</i> (<i>C.</i>) infections. This study aimed to comprehensively evaluate the antifungal efficacy of myricetin (MYR), a natural flavonoid, against both fluconazole (FLC)-resistant and susceptible clinical <i>Candida</i> strains, with a particular focus on its inhibitory effects on <i>C. albicans</i> biofilms. Antifungal susceptibility was evaluated on <i>Candida</i> spp. by the broth microdilution method, and the impact of myricetin on <i>C. albicans</i> biofilms was determined using the Cell Counting Kit-8 (CCK-8) assay. To understand the molecular mechanisms underlying the antibiofilm properties of myricetin, expression analysis of genes in the RAS1/cAMP/EFG1 pathway (<i>ALS3</i>, <i>HWP1</i>, <i>ECE1, UME6</i>, <i>HGC1</i>) and cAMP-dependent protein kinase regulation (<i>RAS1, CYR1, EFG1</i>) involved in the transition from yeast to hyphae was performed. Field emission scanning electron microscopy (FESEM) was used to study the ultrastructural changes and morphological dynamics of <i>Candida</i> biofilms after exposure to MYR and FLC. The in vivo toxicity of myricetin was evaluated by survival analysis using the <i>Galleria mellonella</i> model. Myricetin significantly suppressed key genes related to hyphae development (<i>RAS1</i>, <i>CYR1</i>, <i>EFG1</i>, <i>UME6</i>, and <i>HGC1</i>) and adhesion (<i>ALS3</i> and <i>HWP1</i>) in both clinical and reference <i>Candida</i> strains at a concentration of 640 µg/mL. FESEM analysis revealed that myricetin inhibited hyphae growth and elongation in <i>C. albicans</i>. This study highlights the promising antibiofilm potential of myricetin through a significant inhibition of biofilm formation and hyphal morphogenesis.</p>","PeriodicalId":15878,"journal":{"name":"Journal of Fungi","volume":"11 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}