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At least 19 recordsLinked to original sources
PubMed2025

Integrative glycomic analysis reveals the crucial role of protein glycosylation in fungal pathogenesis.

Protein glycosylation, a co- and post-translational modification that enhances the functional diversity of the proteome, contributes to various molecular and cellular functions by transferring different polysaccharides onto proteins. During the last decade, the role of glycosylation in plant pathogenic fungi has received significant attention, and glycoproteins are expected to play essential roles in various biological processes including pathogenicity. However, the comprehensive functional genetic analyses for protein glycosylation pathways and glycan structures of phytopathogenic fungi are still largely unknown. Here, we investigated the role of protein glycosylation in Fusarium graminearum by identifying 65 putative genes involved in protein glycosylation and characterizing their functions. Through cell wall component profiling and HPLC analysis, we characterized the overall N- and O-glycan structures in F. graminearum and found that deletion of ALG3 and ALG12 led to truncated core N-glycan structures. Quantitative proteomics analysis revealed that the truncated core N-glycans, generated by the loss of two key enzymes in the initial core N-glycosylation pathway, Alg3 and Alg12, affected a wide range of glycoproteins-including transcription factors, phosphatases, kinases, peroxidases, and other proteins involved in various biological processes-ultimately impacting the virulence of F. graminearum. This study elucidates the complex roles of glycosylation, highlighting the connections among genes involved in the protein glycosylation pathway, glycans, and glycoproteins in regulating the general biology and pathogenicity of F. graminearum. It also would be the fungal glycobiology study initiative.

Glycosylation↗
PubMed2025

Stepping out of the dark: how metabolomics shed light on fungal biology.

Metabolomics, a critical tool for analyzing small-molecule metabolites, integrates with genomics, transcriptomics, and proteomics to provide a systems-level understanding of fungal biology. By mapping metabolic networks, it elucidates regulatory mechanisms driving physiological and ecological adaptations. In fungal pathogenesis, metabolomics reveals host-pathogen dynamics, identifying virulence factors like gliotoxin in Aspergillus fumigatus and metabolic shifts, such as glyoxylate cycle upregulation in Candida albicans. Ecologically, it highlights fungal responses to abiotic stressors, including osmolyte production like trehalose, enhancing survival in extreme environments. These insights highlight metabolomics' role in decoding fungal persistence and niche colonization. In drug discovery, it aids target identification by profiling biosynthetic pathways, supporting novel antifungal and nanostructured therapy development. Combined with multi-omics, metabolomics advances insights into fungal pathogenesis, ecological interactions, and therapeutic innovation, offering translational potential for addressing antifungal resistance and improving treatment outcomes for fungal infections. Its progress shed light on complex fungal molecular profiles, advancing discovery and innovation in fungal biology.

Metabolomics↗
PubMed1975

Pathogenesis of fungal infection on heart valve prosthesis.

Four patients with heart valve prostheses developed Candidate endocarditis. At autopsy the foci of infection were confined to patches of neoendocardium that appeared to have developed as ingrowths of host endocardium onto the sewing cloth of the artificial valve. This suggested that one mechanism of fungal infection is related to the presence of the neoendocardium rather than to the cloth or metallic substances of the valve itself. Future studies might be directed toward inhibiting the development of the neoendocardium or to agents preventing its susceptibility to infection.

Adult↗
PubMed2026

Distinct STRIPAK subunits drive conserved and subunit-specific signaling programs in Cryptococcus neoformans.

The striatin-interacting phosphatase and kinase (STRIPAK) complex is a conserved protein phosphatase 2A (PP2A)-associated signaling hub that integrates kinase-phosphatase networks, yet its roles in human fungal pathogens remain poorly defined. Here, we dissected STRIPAK functions in the opportunistic pathogen Cryptococcus neoformans by combining genetic, genomic, virulence, and phosphoproteomic analyses across mutants lacking individual STRIPAK subunits. Loss of the core STRIPAK components via PPH22, FAR8, FAR9, or FAR11 mutations caused severe defects in growth, stress adaptation, cell cycle progression, and morphogenesis, accompanied by widespread aneuploidy and genome instability. In murine infection models, far11Δ strains were avirulent, whereas far9Δ mutants caused delayed but ultimately fatal disease and underwent host-associated genome remodeling, with recovered isolates exhibiting chromosome 11 amplification despite no consistent in vitro fitness advantage. In contrast, deletion of MOB3 produced a hypervirulent phenotype. mob3Δ cells exhibited enhanced transmigration across an in vitro blood-brain barrier model, increased survival in macrophages, and generated small-cell morphotypes, features associated with increased dissemination. Phosphoproteomic profiling revealed extensive and overlapping phosphorylation changes among core STRIPAK mutants, affecting pathways involved in signaling, cytoskeletal, cell cycle control, chromatin regulation, RNA metabolism, and stress responses. Conversely, mob3Δ mutants displayed a smaller, largely distinct phosphoproteomic signature. Network and functional enrichment analyses highlighted STRIPAK-dependent regulation of TORC2-associated signaling, MAPK/GTPase signaling, autophagy, nuclear transport, RNA processing, DNA replication, and ribosome biogenesis. Together, these findings establish STRIPAK as a coordinator of genome stability, morphological plasticity, stress adaptation, and virulence in C. neoformans, and demonstrate that individual STRIPAK subunits drive shared yet divergent signaling outputs that shape host-pathogen interactions.IMPORTANCEFungal pathogens must rapidly adapt their growth, morphology, and stress responses to survive within the host, requiring precise coordination of cellular signaling pathways. The conserved striatin-interacting phosphatase and kinase (STRIPAK) complex controls key developmental programs in eukaryotes, but its roles in fungal pathogenesis are not fully defined. We previously showed that STRIPAK is important for genome stability, development, and virulence in the opportunistic human fungal pathogen Cryptococcus neoformans. Here, we define how individual STRIPAK subunits differentially regulate fungal morphogenesis, genome plasticity, host adaptation, and virulence, revealing both shared and subunit-specific functions within this conserved signaling complex. Core STRIPAK mutants exhibit severe growth and stress-response defects and attenuation of virulence, whereas loss of the Mob3 subunit promotes hypervirulence by enhancing dissemination and persistence within the host. Phosphoproteomic profiling reveals that individual STRIPAK components exert shared yet distinct control over phosphorylation networks that shape host-pathogen interactions, establishing STRIPAK as a central signaling hub and a potential target for antifungal intervention.

Cryptococcus neoformans↗
PubMed2024

Vertebrate and invertebrate animal infection models of Candida auris pathogenicity.

Candida auris is an emerging fungal pathogen with several concerning qualities. First recognized in 2009, it has arisen in multiple geographically distinct genomic clades nearly simultaneously. C. auris strains are typically multidrug resistant and colonize the skin much better than most other pathogenic fungi; it also persists on abiotic surfaces, enabling outbreaks due to transmission in health care facilities. All these suggest a biology substantially different from the 'model' fungal pathogen, Candida albicans and support intensive investigation of C. auris biology directly. To uncover novel virulence mechanisms in this species requires the development of appropriate animal infection models. Various studies using mice, the definitive model, are inconsistent due to differences in mouse and fungal strains, immunosuppressive regimes, doses, and outcome metrics. At the same time, developing models of skin colonization present a route to new insights into an aspect of fungal pathogenesis that has not been well studied in other species. We also discuss the growing use of nonmammalian model systems, including both vertebrates and invertebrates, such as zebrafish, C. elegans, Drosophila, and Galleria mellonella, that have been productively employed in virulence studies with other fungal species. This review will discuss progress in developing appropriate animal models, outline current challenges, and highlight opportunities in demystifying this curious species.

Animals↗
PubMed2026

Integrated Functional Characterization of Hemileia vastatrix Effector Candidates Reveals Coordinated Immune Suppression, Sequential Deployment and Compartment-Specific Targeting.

Coffee leaf rust, caused by the obligate biotrophic fungus Hemileia vastatrix, remains the most destructive disease of coffee worldwide. Although genomic and transcriptomic studies have identified a large number of candidate effectors, experimental evidence supporting their biological roles during infection remains limited. Here, we integrated functional assays, temporal expression profiling during coffee infection and subcellular localization analyses to investigate the biological properties of 44 H. vastatrix effector candidates (HvECs). Using the Pseudomonas fluorescens EtHAn effector delivery system in Nicotiana benthamiana, 15 HvECs consistently suppressed pattern-triggered immunity (PTI), indicating that immune suppression is a widespread property among the H. vastatrix effector repertoire, as assessed in this heterologous system. Five HvECs also attenuated AvrB-triggered effector-triggered immunity (ETI), and three suppressed both PTI and ETI, suggesting that a subset of HvECs targets conserved regulatory nodes shared by these interconnected immune pathways. Temporal expression profiling revealed sequential deployment of HvECs throughout infection, with distinct subsets predominating during pre-biotrophic development, host penetration or biotrophic colonization, consistent with stage-specific functions during fungal pathogenesis. Subcellular localization analyses further showed that HvECs preferentially accumulated in the nucleus or chloroplasts, compartments known as central hubs of plant immune regulation. This study provides the most comprehensive functional characterization of H. vastatrix effector candidates to date, establishes a biologically informed framework for prioritizing candidates for future identification of avirulence determinants recognized by SH resistance genes, and advances our understanding of how the coffee rust fungus orchestrates immune suppression across time and cellular space during pathogenesis.

Nicotiana↗
PubMed2025

Expansion of secreted cystine knot proteins reveals virulence factors in the human fungal pathogen Histoplasma.

Identifying fungal secreted factors that influence host infection remains a key challenge in microbial pathogenesis. While secreted effectors, particularly small cysteine-rich proteins, are well characterized in plant fungal pathogens, their counterparts in mammalian pathogens are understudied. We apply criteria from plant fungal effectors to the mammalian fungal pathogen Histoplasma, yielding a set of putative effectors highly enriched for knottins, proteins that adopt a distinctive cystine knot fold. Using an algorithm, we further identify 25 putative knottins in the Histoplasma genome, revealing a significant expansion of knottin genes. Knottin domains are found in diverse molecules but play an unknown role in virulence. Functional studies of individual Histoplasma knottins demonstrate their critical roles in intracellular survival and host cell lysis during macrophage infection as well as virulence in vivo. These findings highlight the importance of knottins in fungal pathogenesis and suggest their broader relevance for discovering conserved mechanisms of host manipulation.

Histoplasma↗
PubMed1977

Studies on the fungal flora in the lung of human necropsy cases. A critical survey in connection with the pathogenesis of opportunistic fungus infections.

An ecological study was carried out on the fungal flora in the human lung of 159 autopsy cases. Fungi were isolated from 129 cases (81.1%). Filamentous fungi consisting of 918 strains were isolated from 113 cases, and the dominant genera were Aspergillus and Penicillium. Yeasts were isolated from 58 cases, and the dominant genus appeared to be Candida. With morbid anatomical study, the incidence of the fungus isolation was examined from various points of view. It was concluded that even a healthy respiratory parenchyma of the human lung cannot be assumed as aseptic. However, only a few numbers of a few genera of air-born fungi were isolated. Special stress was laid on the exposure of the respiratory parenchyma of the human lung to air-born fungi in connection with the pathogenesis of opportunistic fungus infections.

Adolescent↗
PubMed2026

Genome-Wide Identification and Characterization of Thaumatin-Like Proteins in Potato (Solanum tuberosum L.) and Their Role in Stress Tolerance.

Thaumatin-like proteins (TLPs), part of the Pathogenesis-related protein 5 (PR5) family, play key roles in plant defense against biotic and abiotic stresses. In Solanum tuberosum, a crucial global food crop, the functional diversity of TLPs under stress conditions remains poorly understood, hindering efforts to improve stress tolerance. This study aimed to address this gap by performing a genome-wide identification and characterization of the TLP gene family in potato. We identified 34 TLPs (StTLP1 to StTLP34), distributed across 11 chromosomes. Detailed analyses were conducted on their physicochemical properties, gene structures, conserved motifs, and expression patterns. Promoter analysis revealed multiple stress-responsive cis-elements. Differential expression analysis showed that several StTLPs are significantly regulated in response to salinity, heat, and pathogen infection. Protein-protein interaction and miRNA targeting analyses further highlighted the regulatory networks involving StTLPs in stress adaptation. This study advances the theoretical understanding of the roles of StTLPs in stress response. It provides a valuable genetic resource for future efforts to enhance stress resilience in potato, with potential applications in crop improvement strategies. The 0 l expression of three TLP genes under salt and mannitol stress was verified through real-time PCR analysis after the interval of 15 days. Alterations in the expression patterns of StTLPs offered deeper insight into the involvement of this gene family in diverse abiotic stress responses. All three StTLPs were upregulated under both treatments at 400 mM, relative to their expression at 200 mM. The highest level of upregulation was observed in StTLP20, indicating its prominent role in both stress treatments.

Solanum tuberosum↗
PubMed1976

Renal actinomycosis.

Renal actinomycosis is an endogenous systemic fungal disease with rare renal involvement. Diagnosis, pathogenesis, and therapy are discussed.

Actinomycosis↗
PubMed1979

Phycomycosis of the gastrointestinal tract.

A case of gastrointestinal phycomycosis, a highly lethal fungal infection, is presented. Radiographic, operative and histopathologic features are discussed. Pathogenesis of the disease and the importance of underlying illness, malnutrition, immunosuppression and antibiotic therapy are considered. The literature is reviewed and current approaches to diagnosis and management are summarized. Greater awareness of the clinical setting in which gastrointestinal phycomycosis may develop and earlier consideration of the diagnosis are prerequisite to improved survival.

Female↗
PubMed1976

Genitourinary fungal infections.

Although fungal urinary tract infections occur less frequently than bacterial urinary tract infections their incidence has increased during the last several decades and their clinical importance to the urologist should not be underestimated. Herein the pertinent literature on fungal urinary tract infections is reviewed, with emphasis on the predisposing factors, pathogenesis, host defense mechanisms and the clinical spectrum of the disease. An approach to the evaluation of positive cultures and therapy is presented.

Amphotericin B↗
PubMed2026

Rs_MEP1 Is Required for the Pathogenesis of Rhizoctonia solani AG1-IA in Plants.

Rhizoctonia solani AG1-IA is a polyphagous necrotrophic fungal pathogen that causes sheath blight disease in rice. Efforts are being made to identify pathogenicity-associated genes in R. solani and modulate them to develop a disease control strategy. Here, we investigated the roles of some predicted pathogenicity-associated genes of R. solani that have previously been reported to be upregulated during infection in rice. The tobacco rattle virus-based host-induced gene silencing of the selected pathogenicity-associated genes revealed that silencing of Rs_MEP1, a zinc-containing Peptidase_M43 domain metalloprotease, severely compromises R. solani infection in tomato. Moreover, double-stranded RNA-mediated silencing of Rs_MEP1 prevented R. solani infection in rice. The signal sequence trap assay indicated the secretory nature of Rs_MEP1, and the reporter assay suggested its localization in the plant apoplast. Notably, Agrobacterium-mediated transient overexpression of Rs_MEP1 induces necrotic cell death responses in plants. We provide evidence that Rs_MEP1 interacts with the GH19 family of rice chitinases and potentially modulates their functions. Overall, our study emphasizes that Rs_MEP1 facilitates R. solani in promoting necrotic responses and targets rice GH19 chitinases to impart disease susceptibility in plants. [Formula: see text] Copyright © 2026 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Rhizoctonia↗
PubMed1975

Experimental renal candidiasis in mice and guinea pigs.

As a part of an experimental study of the spread of urogenital infections, male guinea pigs and mice were intravenously injected with a sublethal dose of Candida albicans in a long-time experiment. The kidney was the organ of maximum infection. Spread in the kidney was observed from the cortical and glomerular capillaries, where the injected yeast cells first lodged, but after pseudomycelial transformation penetrated into the Bowman's space and into the lumen of the tubuli. Guinea pigs recovered from the infection. In mice the renal candidiasis progressed and two types of the disease could be distinguished: an acute type with cortical abscesses and a chronic type with partly necrotic tips of the pyramids and adhering fungal masses in the pelves. A similar picture has been observed in man. The pathogenesis of renal candidiasis seems to resemble that of renal tuberculosis.

Acute Disease↗
PubMed1978

A reappraisal of the role of Pityrosporum orbiculare in pityriasis versicolor and the significance of extracellular lipase.

Pityrosporum orbiculare is an obligate lipophilic yeast in vitro, which suggests it possesses an extracellular lipase crucial for nutrition. If present in vivo, the enzyme would enable the yeast to utilize skin surface lipids, which may therfore play an important role in the pathogenesis of pityriasis versicolor. Cultured P. orbiculare and biopsy material from patients with pityriasis versicolor were investigated for the presence of lipase by electron microscope histochemistry. At sites of lipase activity, fatty acid hydrolyzed from Tween 80 substrate reacts with Ca++ ions to form an insoluble Ca++ soap. Exchange of Ca++ with Pb++ enables the sites of lipase activity to be visualized as electron dense deposits of insoluble lead soap. Surface lipase activity was apparent when the technique was applied to P. orbiculare grown on lipid containing medium and its specificity confirmed by removal of substrate and inhibition by di-isopropyl fluorophosphate and quinine hydrochloride, but not by sodium fluoride. When the same technique was applied to stratum corneum infected with Pityrosporum furfur (Malassez), no reaction product could be detected. It is postulated that lipase, although critical for fungal nutrition in vitro, is unlikely to be of importance in vivo. Skin surface lipids are therefore probably not relevant to the pathogenesis of pityriasis versicolor.

Histocytochemistry↗