Search Results (448)

Vairimorpha ceranae (formerly Nosema ceranae) is an obligate intracellular parasite that poses a major threat to the health of the honey bee. Circular RNAs (circRNAs) have been recognized as key regulators in gene expression and pathogen–host interactions. However, their expression patterns and regulatory roles in V. ceranae infection remain largely unexplored. In this study, we performed circRNA profiling in V. ceranae spores (NcCK) and the midguts of Apis mellifera ligustica workers at 7 d post inoculation (dpi) and 10 dpi (Nc7T and Nc10T) based on transcriptome sequencing, followed by in-depth investigation of the regulatory roles of differentially expressed circRNAs (DEcircRNAs). In total, 243 circRNAs were identified in V. ceranae, with lengths predominantly ranging from 201 to 400 nucleotides. Comparative analysis screened 70 and 192 DEcircRNAs in the NcCK vs. Nc7T and NcCK vs. Nc10T comparison groups, respectively, with a significant majority being downregulated. The parental genes of these DEcircRNAs were significantly enriched in fundamental cellular processes and critical pathways such as protein processing in the endoplasmic reticulum and ribosome biogenesis. Additionally, we constructed a competing endogenous RNA network, suggesting that DEcircRNAs could potentially interact with DEmiRNAs to modulate mRNAs associated with fungal proliferation-relevant signaling pathways like MAPK, PI3K–Akt, and cAMP. Moreover, numerous DEcircRNAs were predicted to contain internal ribosome entry site elements, indicative of their potential for protein coding. The back-splicing junctions and expression trends of selected DEcircRNAs were successfully validated by RT-PCR and qRT-PCR. Our data not only offer a valuable resource for future functional studies but also provide a basis for elucidating the circRNA-mediated mechanisms underlying microsporidian pathogenesis and host–pathogen interactions. Full article

Cotton Verticillium wilt (VW), caused by the soil-borne fungus Verticillium dahliae (V. dahliae), is a devastating disease that poses a serious threat to sustainable cotton production worldwide. Protein methylation plays a critical role in fungal adaptation to the host environment and manipulation of plant immunity. Protein arginine methyltransferases (PRMTs) are key enzymes catalyzing arginine methylation, yet their functions in V. dahliae pathogenicity remain largely unexplored. In this study, we identified VdPRMT4 in V. dahliae through homology-based screening. qRT-PCR analysis revealed that VdPRMT4 transcript levels were significantly increased during the early stages of V. dahliae infection in cotton. HIGS assays showed that silencing VdPRMT4 markedly alleviated cotton VW symptoms and reduced fungal biomass in cotton plants. Gene knockout and complementation experiments demonstrated that deletion of VdPRMT4 did not affect hyphal growth but significantly impaired sporulation capacity and severely attenuated pathogenicity on cotton. Transcriptomic analysis further indicated that loss of VdPRMT4 profoundly affected the metabolic pathways of V. dahliae, including protein processing in the endoplasmic reticulum, purine metabolism, and glycerolipid metabolism. Collectively, this study provides the first evidence that VdPRMT4 plays a critical role in stress adaptation and pathogenicity of V. dahliae, offering new insights into fungal pathogenesis and identifying potential targets for VW control. Full article

Safflower (Carthamus tinctorius L.) is an economically important crop, yet its production is severely threatened by fungal diseases including Botrytis cinerea. The molecular mechanism underlying disease resistance in safflower remains largely unclear. Extracellular vesicles (EVs), as vital carriers for cross-kingdom communication and transport, play crucial roles in plant antifungal defense. Lipid transfer proteins (LTPs), members of the pathogenesis-related protein 14 family, have also been shown to be key players in plant disease resistance. The promising resistance-related candidate gene CtLTP8 was previously identified via genome-wide association study (GWAS). In this study, a genome-wide analysis of the LTP gene family in safflower was performed. EVs were isolated from the apoplastic washing fluid of B. cinerea-infected safflower leaves, and proteomic analysis was performed. Numerous proteins associated with disease resistance, including CtLTP8, were detected by proteomic profiling. CtLTP8 was found to be present in EVs through molecular biological experiments. Moreover, stable overexpression of CtLTP8 in safflower significantly increased resistance to B. cinerea. In summary, this study characterized the disease resistance-related proteome of safflower EVs, and verified the presence of CtLTP8 in EVs and its antifungal function, providing valuable gene resources and theoretical support for safflower disease-resistance breeding and research on EV-mediated plant immune mechanisms. Full article

Seborrheic alopecia (SA) is one of the most common forms of hair loss with a complex pathogenesis involving multiple etiological factors. Although the scalp microbiome has been implicated in various scalp disorders, its specific role in the development and progression of SA remains incompletely understood. To characterize the scalp microbiome in SA, we performed high-throughput sequencing of the 16S rRNA gene and ITS region on scalp samples from 41 Chinese SA participants before and after a 12-week intervention with a shampoo containing herbal extracts (ginger root, Polygonum multiflorum, and Platycladus orientalis leaf) and 29 healthy controls. The untreated SA group exhibited significant microbial dysbiosis compared to the healthy controls, characterized by reduced bacterial and fungal alpha diversity and increased relative abundances of Staphylococcus, Cutibacterium, and Malassezia. LEfSe analysis confirmed the significant enrichment of these three genera. Correlation network analysis revealed a substantial restructuring of microbial interactions in the untreated SA group: Staphylococcus and Malassezia lost all positive correlations with other genera, whereas Cutibacterium displayed relatively stable topological relationships. Following the 12-week intervention, the treated SA group showed significant clinical improvement (reduced hair loss and scalp sebum content), along with a restoration of microbial diversity to levels comparable to the healthy group and a normalization of the abundances of Staphylococcus and Malassezia. Our study confirms the critical role of scalp microecological dysbiosis in SA pathogenesis and identifies Staphylococcus and Malassezia as key taxa strongly associated with this dysbiosis. These findings provide a theoretical foundation for developing microbiome-targeted strategies for SA treatment and support the use of multi-targeted, plant-based interventions to restore microbial homeostasis and promote hair growth. Full article

Mucormycosis, triggered by fungi of the order Mucorales, represents a potentially fatal invasive mycosis, with death rates over 50% despite intensive therapy. The COVID-19 pandemic brought a sharp increase in cases, especially in individuals with diabetes mellitus and those undergoing immunosuppressive treatment, emphasizing significant gaps in our comprehension of disease pathogenesis. Emerging molecular studies have highlighted key virulence factors, such as the CotH family of invasins that facilitate endothelial invasion via interaction with glucose-regulated protein 78 (GRP78), complex iron acquisition systems necessary for fungal growth, and the release of mucoricin, a ricin-like toxin that impairs vascular integrity. Host defense depends mainly on innate immunity, with neutrophils and macrophages working as critical effector cells, while adaptive Th1 and Th17 responses aid in the fungal removal. Mucorales use a variety of immune evasion techniques, such as pathogen-associated molecular pattern (PAMP) masking via cell wall transformations, resistance to phagocytic death, and metabolic utilization of host factors including hyperglycemia and increased free iron in diabetic ketoacidosis (DKA). This review summarizes current evidence of the molecular processes underlying mucormycosis pathogenesis, underscoring host–pathogen interactions at the cellular and molecular levels, immune evasion tactics, and translational potential for new diagnostic and therapeutic approaches. Comprehending these molecular processes is crucial for creating efficient therapies against mucormycosis in an era of growing immunocompromised patients and expanding infectious disease synergies. Full article

Members of Fusarium oxysporum species complex (FOSC) and Fusarium solani species complex (FSSC) are common etiologic agents of opportunistic mycoses. Their hyphae grow via apical extension followed by invasion of host epithelial surfaces, particularly corneal and epithelial tissues. Thigmotropism is the contact-sensing response of these growing hyphae to change the direction of their apical growth in response to changes in the topography of their contacted surfaces, such as clefts between adjacent host cells. Investigations of fungal thigmotropism among etiologic agents of opportunistic mycoses are sparse. In this study, we assessed thigmotropic capacities of 10 fusarial strains. Thigmotropic activity was quantified using a chemotaxicell system followed by scanning electron microscopy (SEM). Isolates belonging to the FSSC had significantly greater rates of thigmotropism than FOSC strains (p < 0.0001). In summary, this work offers a creative method to assess thigmotropism, a crucial aspect of fungal pathogenesis, and, secondly, demonstrates potent thigmotropic capacities of fusarial isolates belonging to the FSSC. Full article

The remarkable ecological success of fungi is supported by their capacity for rapid and often reversible molecular responses to fluctuating environments. While conventional evolutionary theory has largely emphasized mutation and selection as central drivers of adaptation, many environmentally responsive fungal traits are also shaped by molecular processes that generate reversible phenotypic variation on ecological or developmental timescales. This review synthesizes current knowledge on reversible genetic and epigenetic mechanisms underlying fungal phenotypic plasticity by integrating insights from programmed genetic rearrangements such as mating-type switching, transposable element activity, variation in tandem repeats and the behavior of accessory chromosomes, together with dynamic epigenetic processes including histone modifications, DNA methylation, chromatin remodeling and RNA mediated regulation. Together, these mechanisms form an interconnected framework that enables rapid and, in many cases, reversible phenotypic diversification, although their consequences range from transient regulatory shifts to partially or fully irreversible sequence-level changes. We highlight the molecular machinery that governs reversibility and its evolutionary implications for fungal pathogenesis, symbiosis, and biotechnology. By uniting genetic and epigenetic perspectives, this review advances a holistic framework in which reversibility is treated as a key property of fungal phenotypic plasticity, helping fungi balance stability with flexibility under environmental challenge. Understanding these mechanisms provides new insights into fungal evolution, and opens new avenues for antifungal intervention and the rational design of industrially valuable fungal strains. Full article

Histidine triad (HIT) family proteins contain a conserved histidine triad motif and play key roles in fungal metabolism and pathogenicity. This study focused on VD9136, a member of the HIT family in Verticillium dahliae, aiming to elucidate its biological function and mechanism underlying its role in cotton pathogenesis. A systematic investigation of the VD9136 gene in V. dahliae was conducted using bioinformatics analysis, gene knockout, genetic complementation, and pathogenicity assays. The results showed that VD9136 protein consists of 136 amino acids and is a stable, neutral, and weakly hydrophilic protein that lacks transmembrane domains and signal peptides; it is localized to the extracellular space via a non-classical secretion pathway. Its secondary structure is predominantly composed of α-helices and random coils. Phylogenetic analysis revealed that VD9136 is closely related to VliHIT, a homologous protein from V. longisporum, the pathogen responsible for Verticillium wilt in rapeseed. The promoter region of VD9136 contains multiple cis-acting elements, including light-responsive, hormone-responsive, and stress-responsive elements, indicating that its transcription may be regulated by multiple signaling pathways. VD9136 was significantly upregulated during the early stage of cotton infection (6–24 h post-inoculation). Pathogenicity assays demonstrated that V. dahliae knockout mutants lacking VD9136 exhibited a significant reduction in virulence, as evidenced by a lower disease index, decreased fungal biomass within plant tissues, and attenuated vascular browning in cotton plants. The pathogenic phenotype was successfully restored in genetic complementation strains. This study identified VD9136 as a key regulatory factor in the pathogenic process of V. dahliae, and its loss of function reduces the pathogenicity of V. dahliae. The findings provide a theoretical basis for elucidating the pathogenic mechanism of cotton Verticillium wilt and for developing corresponding prevention and control strategies. Full article

The genomic basis underlying the remarkable ecological flexibility of endophytic fungi (EF), particularly their potential to transition between symbiotic, saprophytic, and pathogenic lifestyles, remains poorly understood. Through comparative genomics of 75 Ascomycota and a validation set of 36 Fusarium genomes, we uncovered a distinct pattern of genome evolution in EF, contrasting with the well-known “gene loss” model in obligate symbionts. Our analysis reveals that EF genomes are significantly expanded, primarily driven by the accumulation of DNA transposable elements (TEs). Crucially, this TE-mediated genomic plasticity is coupled with the retention and significant expansion of gene families for both saprotrophy and potential pathogenesis. We propose a novel “dual-trophic potential” model: TE-driven genomic expansion and plasticity provide the genetic raw material for EF to maintain a versatile repertoire of ecological tools, facilitating adaptive shifts across the endophytic–saprophytic–pathogenic continuum. This study reframes our understanding of fungal endophytism from a static symbiotic state to a dynamic, genetically enabled ecological strategy. Full article

Pneumocystis is a respiratory fungal pathogen that causes life-threatening pneumonia in immunocompromised patients. While Pneumocystis can colonize healthy hosts by resisting and transiently evading innate immunity, a functional adaptive immune response is essential to prevent progressive infection. Impairments in adaptive immunity, particularly defects in CD4⁺ T cell function, are strongly associated with the development of severe Pneumocystis pneumonia (PCP) in humans and a wide range of mammalian species. Immune activation by Pneumocystis has strong genetic determinants, and a major gap in our understanding of PCP pathogenesis lies in uncovering the mechanisms by which Pneumocystis escapes alveolar macrophages and evades pulmonary innate immunity. Prior research determined that FVB/NJ mice display an unusual resistance to Pneumocystis infection. Further susceptibility testing across several inbred mouse strains revealed that the AKR/J strain, which is phylogenetically distant from the FVB/NJ strain, also exhibits a rarely described form of protective innate immunity against PCP. Notably, the mechanism of AKR/J resistance does not require CD4⁺ or CD8⁺ T lymphocytes. However, depleting alveolar macrophages prior to infection rendered AKR/J mice susceptible to PCP, highlighting the critical role of macrophages for this protective innate immune response. These novel findings establish the AKR/J inbred strain as a valuable model for investigating the interaction between Pneumocystis and macrophages, offering a unique opportunity to explore how these interactions lead to differential outcomes between resistant and susceptible mouse strains. Additionally, it may offer key insights into the mechanisms by which Pneumocystis evades macrophage-mediated innate immunity in the majority of mammalian hosts, including humans. Full article

Background: Recurrent vulvovaginal candidiasis (RVVC) is a chronic inflammatory disease primarily caused by Candida albicans (C. albicans). Its pathogenesis remains incompletely understood, and clinical management is challenged by recurrence and drug resistance. Ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, has been implicated in various infectious and inflammatory diseases. However, its role in RVVC remains unclear, with a particular lack of evidence from clinical samples and animal experiments. Objective: This study aimed to investigate the association between RVVC and ferroptosis. First, we analyzed high-throughput sequencing data from human RVVC samples in the Gene Expression Omnibus (GEO) database to identify the expression profile of ferroptosis-related genes. Second, using an established murine model of chronic vulvovaginal candidiasis (CVVC), we validated changes in ferroptosis-related markers in vaginal tissues in vivo. Furthermore, an in vitro model of C. albicans-infected bone marrow-derived macrophages (BMDMs) was employed to explore the underlying mechanisms. This study provides experimental evidence for elucidating the pathogenesis of RVVC and exploring novel therapeutic strategies. Methods: The RVVC-related gene expression dataset GSE278036 was obtained from the GEO database. Differentially expressed genes (DEGs) were screened using the DESeq2 algorithm and intersected with ferroptosis-related genes from the FerrDb database to identify key targets. A protein–protein interaction (PPI) network was constructed using the STRING database and Cytoscape software, and hub genes were identified via the Betweenness centrality algorithm. Functional and pathway analyses, including gene set enrichment analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways, were performed. Immune infiltration analysis characterized the immune microenvironment in RVVC patients. A CVVC mouse model was established in vivo, and a C. albicans-BMDMs infection model was established in vitro. The ferroptosis inhibitor ferrostatin-1 (Fer-1) was administered to investigate the pathological function and regulatory mechanisms of ferroptosis in RVVC at the molecular, cellular, and tissue levels. Results: Differential analysis identified 3132 DEGs in RVVC, which intersected with ferroptosis-related genes to yield 194 key targets. Among them, 20 hub genes were identified, including ferroptosis regulators and inflammatory factors. Functional enrichment analysis confirmed that these shared targets regulate RVVC pathology through a “ferroptosis-inflammation-immunity” multi-pathway network. Immune infiltration analysis revealed a specific immune disorder in RVVC patients characterized by “activation of the pro-inflammatory innate immune axis and suppression of the adaptive immune axis,” which was closely associated with ferroptosis-related genes. In vivo and in vitro experiments confirmed that C. albicans infection induced ferroptosis in vaginal tissues and macrophages, as manifested by lipid ROS accumulation, Fe²⁺ overload, GSH depletion, downregulation of GPX4 and SLC7A11, upregulation of ACSL4, 4-HNE, and MDA, and mitochondrial structural damage. Macrophages were identified as key target cells for ferroptosis, and their ferroptosis led to impaired antifungal function. Fer-1 treatment significantly inhibited ferroptosis, reduced vaginal histopathological damage and inflammatory cell infiltration, decreased fungal burden, downregulated abnormally elevated inflammatory factors, and restored Th1/Th2 immune balance. Furthermore, Fer-1 preserved macrophage viability and enhanced their antifungal killing capacity. Conclusions: This study provides the first evidence linking RVVC to ferroptosis through a combination of clinical data analysis and experiments, suggesting that ferroptosis is involved in its pathological process. These findings offer a new perspective for elucidating RVVC pathogenesis and developing targeted therapeutic strategies. Full article

The CFEM (Common in Fungal Extracellular Membrane) domain defines a family of cysteine-rich proteins unique to fungi, playing pivotal roles in host–pathogen interactions. However, the repertoire and functions of CFEM proteins in the broad-host-range necrotrophic pathogen Sclerotinia sclerotiorum remain largely unexplored. Through genome-wide bioinformatic analysis, we identified 13 CFEM-containing proteins (SsCFEM1–13) in S. sclerotiorum. Characterization revealed substantial diversity in their physicochemical properties, domain architecture, and predicted subcellular localization. Ten proteins possess a secretion signal, with six predicted to be GPI-anchored and three classified as high-confidence effectors. Members lacking transmembrane domains were predicted to adopt the conserved CFEM “helical-basket” fold. Phylogenetic analysis grouped SsCFEMs into two distinct clades and indicated a complex evolutionary history involving both conserved ancestry and lineage-specific expansion. Transcriptomic profiling showed that most genes were upregulated during early infection of various host plants, with SsCFEM8 exhibiting particularly strong and consistent induction. Crucially, transient expression assays in Nicotiana benthamiana revealed that several SsCFEM proteins, notably SsCFEM4 and SsCFEM9, function as cell death suppressors, validating their predicted effector roles and identifying key virulence candidates. This study provides the first comprehensive catalog and functional prediction of the CFEM protein family in S. sclerotiorum, establishing a foundation for future mechanistic studies on their roles in the pathogenesis of this devastating fungal pathogen. Full article

Lysin motif (LysM) domain-containing proteins are widespread in prokaryotes and eukaryotes, and play crucial roles in microbe-host interactions. In recent decades, a large number of LysM domain-containing proteins have been identified and confirmed to participate in various biological processes, including microbial growth, fungal pathogenesis, and recognition of pathogens by plant immune receptors. Emerging evidence has shown that some LysM domain-containing proteins in plant pathogenic fungi have evolved as key virulence factors. They manipulate host immune responses mainly by interfering with the plant’s perception of chitin, a core pathogen-associated molecular pattern (PAMP) of fungal cell walls. However, the functions of LysM domain-containing proteins in plant pathogenic fungi have not been systematically summarized. In this review, we discuss the latest advances in the structural characteristics, classification, and functional mechanisms of these proteins, as well as their applications in plant disease control. We also propose the current challenges and future research directions in this field. This review aims to deepen the understanding of the molecular mechanisms underlying plant-fungal interactions mediated by LysM domain-containing proteins and provide theoretical references for developing novel and environmentally friendly strategies for fungal disease management in agriculture. Full article

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis, which can progress to end-stage liver disease and even hepatocellular carcinoma. Its onset is typically triggered by complex interactions between genetic and environmental factors. In recent years, epidemiological and mechanistic studies have highlighted bacterial and fungal infections as potential key environmental factors in PBC pathogenesis. Bacteria may be associated with PBC autoimmunity through mechanisms such as molecular mimicry. Gut microbiota dysbiosis has been linked to aberrant immune recognition, altered metabolites, and intestinal barrier disruption, which may contribute to the aggravation of liver injury. Case reports of fungal infections suggest an association with poor prognosis in PBC, although the underlying mechanisms remain to be elucidated. This review systematically summarizes existing clinical epidemiological data, microbiome association studies, and mechanistic evidence; synthesizes the possible molecular mechanisms linking bacterial infections to PBC development and progression; discusses the potential role of the gut microbiota in PBC progression; and analyzes the possible molecular mechanisms underlying the poor prognosis associated with fungal infections in PBC. This study aims to provide valuable insights for developing optimal prevention, diagnosis, and treatment strategies targeting bacterial and fungal infections in PBC. Full article

Rapid responses to environmental changes are essential for maintaining fitness. In pathogenic fungi such as the dermatophyte Trichophyton interdigitale, appropriate responses to environmental shifts determine successful infection. Transcriptional regulation and alternative splicing (AS) are key modulators of fungal adaptation and pathogenesis. Here, we validated the role of the transcription factor PacC in coordinating AS in T. interdigitale grown in infection-mimicking medium. RNA-seq analysis of a ΔpacC mutant revealed a predominance of intron retention events, mainly involving introns 1 and 2, indicating defective splicing and potential nonsense-mediated decay of genes related to ion transport, metabolism, and genome maintenance. These alterations compromised energy balance, ergosterol biosynthesis, and cellular homeostasis. PacC-dependent AS generated alternative isoforms of cytoskeletal and metabolic proteins, including myosin-1 and a GH3 β-glucosidase, potentially modulating enzymatic activity, metabolic burden, and cell wall remodeling during infection. Exon-skipping in the chromatin remodeler RSC1 suggests PacC involvement in epigenetic regulation under host-mimicking conditions. Transmission electron microscopy revealed possible Woronin bodies, cytoplasmic disruption, and cell wall thinning in the mutant. Overall, PacC integrates transcriptional and post-transcriptional regulation to promote adaptation, survival, and virulence, highlighting AS as a regulatory layer linking environmental sensing to metabolic and epigenetic plasticity in pathogenic fungi. Full article