Frontiers in fungal biology最新文献

{"title":"The fungus <i>Escovopsis</i> (<i>Ascomycota</i>: <i>Hypocreales</i>): a critical review of its biology and parasitism of attine ant colonies.","authors":"Simon Luke Elliot, Quimi Vidaurre Montoya, Marcela Cristina Silva Caixeta, Andre Rodrigues","doi":"10.3389/ffunb.2024.1486601","DOIUrl":"10.3389/ffunb.2024.1486601","url":null,"abstract":"<p><p>Two biological phenomena that contribute to increasing complexity in biological systems are mutualistic symbiotic interactions and the evolution of sociality. These two phenomena are also of fundamental importance to our understanding of the natural world. An organism that poses a threat to one or both of these is therefore also of great interest as it represents a challenge that mutualistic symbioses and social organisms have to overcome. This is the case with the fungus <i>Escovopsis</i> (<i>Ascomycota</i>: <i>Hypocreales</i>), which attacks the fungus garden of attine ants (<i>Formicidae</i>: <i>Attina</i>) such as the leaf cutters. This parasite has attracted much high-profile scientific interest for considerable time, and its study has been fruitful in understanding evolutionary, ecological and behavioural processes. Despite this, much of the biology and ecology of this organism remains unknown. Here we discuss this fungus and three sister genera (<i>Escovopsioides</i>, <i>Luteomyces</i> and <i>Sympodiorosea</i>) that until recently were considered as a single group. We first describe its position as the most highly specialised microbial symbiont in this system other than the mutualistic fungal cultivar itself and as that of greatest scientific interest. We then review the taxonomic history of the group and its macroevolution and biogeography. We examine what we know of its life cycle in the field - surprisingly little is known of how it is transmitted between colonies, but we explain what is known to date. We then review how it interacts with its host(s), first at the level of its direct interaction with the basidiomycete host fungi wherein we show the evidence for it being a mycoparasite; then at the colony level where empirical evidence points towards it being a parasite with a very low virulence or even merely a opportunist. Finally, we offer directions for future research.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"5 ","pages":"1486601"},"PeriodicalIF":2.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can whole genome sequencing resolve taxonomic ambiguities in fungi? The case study of <i>Colletotrichum</i> associated with ferns.","authors":"Andrea Menicucci, Salvatore Iacono, Madalena Ramos, Chiara Fiorenzani, Natalia Aparecida Peres, Lavern Wayne Timmer, Antonio Prodi, Riccardo Baroncelli","doi":"10.3389/ffunb.2025.1540469","DOIUrl":"https://doi.org/10.3389/ffunb.2025.1540469","url":null,"abstract":"<p><strong>Introduction: </strong>The genus <i>Colletotrichum</i> comprises numerous fungal species with diverse ecological roles, including plant pathogenic, endophytic, and saprophytic lifestyles. Accurate species identification is crucial for understanding host-pathogen interactions, disease epidemiology, and fungal ecology. However, taxonomic classification within <i>Colletotrichum</i> remains challenging due to genetic complexity and phenotypic plasticity. Conventional approaches such as single-gene analyses and multilocus sequence typing (MLST) frequently fail to resolve closely related taxa, leading to misidentifications that hinder species delimitation and comparative evolutionary studies. Whole-genome sequencing (WGS) offers a promising alternative by providing genome-wide resolution for phylogenetic analysis. This study investigates <i>Colletotrichum</i> isolates associated with the fern <i>Rumohra adiantiformis</i> and evaluates the effectiveness of WGS in addressing taxonomic uncertainties.</p><p><strong>Methods: </strong>A total of 18 <i>Colletotrichum</i> isolates, including fern-associated strains, were analyzed. Genomic DNA was extracted and sequenced using the Illumina NovaSeq platform. High-quality genome assemblies were generated, and gene prediction was conducted using AUGUSTUS. Orthogroup assignment and phylogenomic analysis were performed based on single-copy orthologs, and phylogenetic trees were constructed using MLST and WGS-based approaches. Comparative analyses were carried out to assess the taxonomic resolution provided by WGS in relation to traditional methods.</p><p><strong>Results: </strong>Genome-wide phylogenomic analysis revealed distinct evolutionary lineages among <i>Colletotrichum</i> isolates that MLST failed to resolve, highlighting host and geographic differentiation. High-quality genome assemblies were obtained, with 98.3% of genes assigned to orthogroups, indicating strong genomic conservation. Phylogenetic analyses confirmed a close relationship between <i>Rumohra adiantiformis</i>-associated isolates and <i>Colletotrichum filicis</i>, reinforcing the effectiveness of WGS in species identification.</p><p><strong>Discussion: </strong>These findings demonstrate the superiority of WGS over MLST in resolving species boundaries and reconstructing evolutionary relationships. The enhanced resolution provided by genome-wide data enables more accurate taxonomic classification, reducing misidentifications and improving our understanding of fungal biodiversity. By refining <i>Colletotrichum</i> taxonomy, WGS facilitates ecological and pathogenic studies, offering a robust framework for future research in fungal systematics and plant pathology. As sequencing technologies continue to advance, WGS is expected to become a standard tool for fungal species delineation and evolutionary studies.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"6 ","pages":"1540469"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First report of the emerging pathogenic yeast <i>Candida palmioleophila</i> in commercially relevant fish from southeastern Brazil.","authors":"Manoel M E Oliveira, Viviane Felix Moraes Lima, Gisela Lara da Costa, Barbara de Oliveira Baptista, Julia Auad Augusto, Rachel Ann Hauser-Davis","doi":"10.3389/ffunb.2025.1545572","DOIUrl":"10.3389/ffunb.2025.1545572","url":null,"abstract":"<p><p>The emerging fungal pathogen <i>Candida palmioleophila</i> (<i>C. palmioleophila</i>) has been increasingly detected in environmental and animal samples, although studies in this regard are still scarce, especially in fisheries contexts. This study reports the first-time detection of <i>C. palmioleophila</i> in a commercially relevant fish species belonging to the Sciaenidae family (<i>Cynoscion</i> sp.), indicating its potential emergence as a pathogen in Brazil. We applied CHROMagar Candida Plus medium identification associated to Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for the identification of <i>C. palmioleophila</i> isolates. Although only one fish specimen was shown to be contaminated by <i>C. palmioleophila</i>, this study provides the first evidence of this yeast circulating in commercially relevant fish species in Brazil, highlighting the potential risks associated with this emerging pathogen.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"6 ","pages":"1545572"},"PeriodicalIF":2.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dispensable genome and segmental duplications drive the genome plasticity in <i>Fusarium solani</i>.","authors":"Abbeah Navasca, Jatinder Singh, Viviana Rivera-Varas, Upinder Gill, Gary Secor, Thomas Baldwin","doi":"10.3389/ffunb.2025.1432339","DOIUrl":"10.3389/ffunb.2025.1432339","url":null,"abstract":"<p><p><i>Fusarium solani</i> is a species complex encompassing a large phylogenetic clade with diverse members occupying varied habitats. We recently reported a unique opportunistic <i>F. solani</i> associated with unusual dark galls in sugarbeet. We assembled the chromosome-level genome of the <i>F. solani</i> sugarbeet isolate strain SB1 using Oxford Nanopore and Hi-C sequencing. The average size of <i>F. solani</i> genomes is 54 Mb, whereas SB1 has a larger genome of 59.38 Mb, organized into 15 chromosomes. The genome expansion of strain SB1 is due to the high repeats and segmental duplications within its three potentially accessory chromosomes. These chromosomes are absent in the closest reference genome with chromosome-level assembly, <i>F. vanettenii</i> 77-13-4. Segmental duplications were found in three chromosomes but are most extensive between two specific SB1 chromosomes, suggesting that this isolate may have doubled its accessory genes. Further comparison of the <i>F. solani</i> strain SB1 genome demonstrates inversions and syntenic regions to an accessory chromosome of <i>F. vanettenii</i> 77-13-4. The pan-genome of 12 publicly available <i>F. solani</i> isolates nearly reached gene saturation, with few new genes discovered after the addition of the last genome. Based on orthogroups and average nucleotide identity, <i>F. solani</i> is not grouped by lifestyle or origin. The pan-genome analysis further revealed the enrichment of several enzymes-coding genes within the dispensable (accessory + unique genes) genome, such as hydrolases, transferases, oxidoreductases, lyases, ligases, isomerase, and dehydrogenase. The evidence presented here suggests that genome plasticity, genetic diversity, and adaptive traits in <i>Fusarium solani</i> are driven by the dispensable genome with significant contributions from segmental duplications.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"6 ","pages":"1432339"},"PeriodicalIF":2.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi <i>Alternaria alternata</i> BRN05 isolated from seeds of <i>Swietenia macrophylla</i> king.","authors":"Piyush Kumar, Sai Anand Kannakazhi Kantari, Ranendra Pratap Biswal, Prasanth Ghanta, Malleswara Dharanikota","doi":"10.3389/ffunb.2025.1447609","DOIUrl":"10.3389/ffunb.2025.1447609","url":null,"abstract":"<p><p>There is a growing demand for new diabetes drugs with fewer side effects to replace current medications known for their adverse effects. Inhibition of α-glucosidase responsible for postprandial hyperglycemia among diabetes patients is a promising strategy for managing the disease. This study aims to explore and identify novel bioactive metabolites with anti-diabetes potential from <i>Alternaria alternata</i> BRN05, an endophytic fungus isolated from a well-known medicinal plant <i>Swietenia macrophylla</i> King. Ethyl acetate extracts of <i>Alternaria alternata</i> BRN05 grown in full-strength (EFS) and quarter-strength (EQS) media, respectively were evaluated for their α-glucosidase inhibitory activities. Based on IC₅₀ values, EQS exhibited significantly greater inhibitory activity (0.01482 ± 1.809 mg/mL) as compared to EFS (1.16 ± 0.173 mg/mL) as well as acarbose control (0.494 ± 0.009 mg/mL). EFS and EQS were subjected to metabolic profiling using Ultra-High-Performance Liquid Chromatography - Electrospray Ionization - Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-ESI-QTOF-MS). A total of nineteen metabolites from EFS and twenty from EQS were tentatively identified based on MS/MS fragmentation. Molecular docking analysis revealed that twelve among these exhibited greater binding energies than that of acarbose (-6.6 kcal/mol). Molecular Dynamics (MD) simulations of 3',4',7-trihydroxyisoflavanone (THF) and alternariol 9-methyl ether (AME) from EQS, exhibiting high binding energies (-7.5 and -7 kcal/mol, respectively), were performed to investigate their interactions with human intestinal α-glucosidase. Results suggest THF possesses strong inhibitory potential, making it a promising candidate for diabetes management.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"6 ","pages":"1447609"},"PeriodicalIF":2.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSE-8, a filamentous fungus-specific Shr3-like chaperone, facilitates endoplasmic reticulum exit of chitin synthase CHS-3 (class I) in <i>Neurospora crassa</i>.","authors":"Samantha Verónica González-Téllez, Meritxell Riquelme","doi":"10.3389/ffunb.2024.1505388","DOIUrl":"10.3389/ffunb.2024.1505388","url":null,"abstract":"<p><p>Chitin is a crucial structural polysaccharide in fungal cell walls, essential for maintaining cellular plasticity and integrity. Its synthesis is orchestrated by chitin synthases (CHS), a major family of transmembrane proteins. In <i>Saccharomyces cerevisiae</i>, the cargo receptor Chs7, belonging to the Shr3-like chaperone family, plays a pivotal role in the exit of Chs3 from the endoplasmic reticulum (ER) and its subsequent activity in the plasma membrane (PM). However, the auxiliary machinery responsible for CHS trafficking in filamentous fungi remains poorly understood. The <i>Neurospora crassa</i> genome encodes two orthologues of Chs7: chitin synthase export (CSE) proteins CSE-7 (NCU05720) and CSE-8 (NCU01814), both of which are highly conserved among filamentous fungi. In contrast, yeast forms only possess a single copy CHS export receptor. Previous research highlighted the crucial role of CSE-7 in the localization of CHS-4 at sites of cell wall synthesis, including the Spitzenkörper (SPK) and septa. In this study, CSE-8 was identified as an export protein for CHS-3 (class I). In the <i>Δcse-8</i> knockout strain of <i>N. crassa</i>, CHS-3-GFP fluorescence was absent from the SPK or septa, indicating that CSE-8 is required for the exit of CHS-3 from the ER. Additionally, sexual development was disrupted in the <i>Δcse-8</i> strain, with 20% of perithecia from homozygous crosses exhibiting two ostioles. A <i>Δcse-7;Δcse-8</i> double mutant strain showed reduced N-acetylglucosamine (GlcNAc) content and decreased radial growth. Furthermore, the loss of cell polarity and the changes in subcellular distribution of CSE-8-GFP and CHS-3-GFP observed in hyphae under ER stress induced by the addition of tunicamycin and dithiothreitol reinforce the hypothesis that CSE-8 functions as an ER protein. The current evidence suggests that the biogenesis of CHS exclusive to filamentous fungi may involve pathways independent of CSE-mediated receptors.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"5 ","pages":"1505388"},"PeriodicalIF":2.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new name for an old problem-<i>Colletotrichum cigarro</i> is the cause of St John's wilt of <i>Hypericum perforatum</i>.","authors":"Lana-Sophie Kreth, Ulrike Damm, Monika Götz","doi":"10.3389/ffunb.2024.1534080","DOIUrl":"10.3389/ffunb.2024.1534080","url":null,"abstract":"<p><p>A major problem for St John's wort (<i>Hypericum perforatum</i>) is St John's wilt, which can lead to reduced crop yields and even complete crop losses. In the past, the pathogen was referred to as <i>Colletotrichum gloeosporioides</i> or occasionally as <i>Colletotrichum</i> cf. <i>gloeosporioides</i> based on morphology. Although a strain from this host had been re-identified as <i>C. cigarro</i> in taxonomic studies, there is uncertainty about the identity of the St John's wilt pathogen, which is generally still addressed as <i>C. gloeosporioides</i> in applied science. In a multi-locus [internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), and glutamine synthetase (GS)] analysis of the <i>C. gloeosporioides</i> species complex, all isolates obtained from newly collected symptomatic <i>H. perforatum</i> stems and seeds from Germany and Switzerland were identified as <i>C. cigarro.</i> Although they belonged to the same haplotype, the morphology of the isolates was very variable. Pathogenicity tests demonstrated that only <i>C. cigarro</i> strains from <i>H. perforatum</i> cause symptoms on <i>H. perforatum</i>, whereas other <i>Colletotrichum</i> species tested only caused latent infection of <i>H. perforatum</i>.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"5 ","pages":"1534080"},"PeriodicalIF":2.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Fungal virulence.","authors":"Jaime David Acosta-España, Antonio José de Jesus Evangelista, Jonathas Sales de Oliveira, Rosana Serpa","doi":"10.3389/ffunb.2024.1530202","DOIUrl":"https://doi.org/10.3389/ffunb.2024.1530202","url":null,"abstract":"","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"5 ","pages":"1530202"},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and screening of wood-decaying fungi for lignocellulolytic enzyme production and bioremediation processes.","authors":"Anna Civzele, Linda Mezule","doi":"10.3389/ffunb.2024.1494182","DOIUrl":"10.3389/ffunb.2024.1494182","url":null,"abstract":"<p><p>The growing demand for novel enzyme producers to meet industrial and environmental needs has driven interest in lignocellulose-degrading fungi. In this study, lignocellulolytic enzyme production capabilities of environmental fungal isolates collected from boreal coniferous and nemoral summer green deciduous forests were investigated, using Congo Red, ABTS, and Azure B as indicators of cellulolytic and ligninolytic enzyme productions. Through qualitative and quantitative assays, the study aimed to identify promising species for lignocellulose-degrading enzyme secretion and assess their potential for biotechnological applications. Primary screening tests showed intensive enzyme secretion by certain isolates, particularly white rot fungi identified as <i>Trametes pubescens</i> and <i>Cerrena unicolor</i>. These fungi exhibited high efficiency in degrading Congo Red and Azure B. The isolates achieved up to a 93.30% decrease in Congo Red induced color intensity and over 78% decolorization of Azure B within 168 hours. Within 336 hours, these fungi reached nearly 99% removal of Congo Red and up to 99.79% decolorization of Azure B. Enzyme activity analysis confirmed the lignin-degrading capabilities of <i>T. pubescens</i>, which exhibited laccase activity exceeding 208 U/mL. Furthermore, <i>Fomitopsis pinicola</i> showed the highest cellulose-degrading potential among the studied fungi, achieving cellulase activity over 107 U/L during Congo Red decolorization. Previously undescribed enzyme-producing species, such as <i>Peniophora cinerea</i>, <i>Phacidium subcorticalis</i>, and <i>Cladosporium pseudocladosporioides</i>, also demonstrated promising lignocellulolytic enzyme production potential, achieving up to 98.65% and 99.80% decolorization of Congo Red and Azure B, respectively. The study demonstrates novel candidates for efficient lignocellulolytic enzyme production with broad biotechnological applications such as biomass conversion, wastewater treatment, textile dye and other complex chemical removal, and environmental remediation.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"5 ","pages":"1494182"},"PeriodicalIF":2.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimal domain peptides derived from enterocins exhibit potent antifungal activity.","authors":"Dorrian G Cohen, Theresa M Heidenreich, Jason W Schorey, Jessica N Ross, Daniel E Hammers, Henry M Vu, Thomas E Moran, Christopher J Winski, Peter V Stuckey, Robbi L Ross, Elizabeth Arsenault Yee, Felipe H Santiago-Tirado, Shaun W Lee","doi":"10.3389/ffunb.2024.1506315","DOIUrl":"10.3389/ffunb.2024.1506315","url":null,"abstract":"<p><p>The antimicrobial peptide (AMP) circularized bacteriocin enterocin AS-48 produced by <i>Enterococcus</i> sp. exhibits broad-spectrum antibacterial activity via dimer insertion into the plasma membrane to form membrane pore structures, compromising membrane integrity and leading to bactericidal activity. A specific alpha-helical region of enterocin AS-48 has been shown to be responsible for the membrane-penetrating activity of the peptide. The canon syn-enterocin peptide library, generated using rational design techniques to have ninety-five synthetic peptide variants from the truncated, linearized, membrane-interacting domain of enterocin AS-48, was screened against three clinically relevant fungal strains: <i>Cryptococcus neoformans</i>, <i>Candida albicans</i>, and <i>Candida auris</i> for potential antifungal activity. Twelve peptides exhibited antifungal activity against <i>C. neoformans</i>, and two peptides exhibited activity against <i>C. albicans</i>. The fourteen active antifungal peptides were minimally cytotoxic to an immortalized human keratinocyte cell line (HaCats). Four select peptides were identified with minimum inhibitory concentrations (MICs) below 8 µM against <i>C. neoformans</i>. In 36-hour cell growth tests with these fungicidal peptides, fungicidal peptide no. 32 displayed inhibitory properties comparable to the leading antifungal medication fluconazole against <i>C. neoformans</i>. Screening of peptide no. 32 against a deletion library of <i>C. neoformans</i> mutants revealed that the mechanism of action of peptide no. 32 may relate to multivesicular bodies (MVBs) or polysaccharide capsule targeting. These findings importantly demonstrate that naturally derived AMPs produced by bacteria can be sourced, engineered, and modified to exhibit potent antifungal activity. Our results will contribute to the development of broad treatment alternatives to fungal infections and lend themselves to direct implications for possible treatment options for <i>C. neoformans</i> infections.</p>","PeriodicalId":73084,"journal":{"name":"Frontiers in fungal biology","volume":"5 ","pages":"1506315"},"PeriodicalIF":2.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}