Search Results (210)

Phytopathogenic fungi pose a constant threat to worldwide agricultural production. Given the widespread development of fungicide resistance and increasing environmental and regulatory constraints, precision disease-control strategies are urgently needed to enhance selectivity, durability, and sustainability. This review critically examines recent advances in targeted fungicide discovery against phytopathogenic fungi. We categorize these strategies into three complementary groups: (1) targeting fungal biological processes that are essential or infection-associated; (2) disarming pathogen virulence by interfering with immune evasion and effector-mediated interactions; and (3) activating or redirecting host defence through host-directed or dual-action interventions. We compare these strategies with respect to mechanistic rationale, expected selectivity, resistance risk, and field-deployment challenges. Additionally, we discuss emerging enabling technologies—including compound repurposing, structural biology, and artificial intelligence-assisted fungicide design—that accelerate target identification and lead optimization. These strategies have begun to facilitate the discovery of compounds with improved specificity and disease-control potential. We believe that the integrated application of these approaches may support the development of more selective and potentially durable disease-control agents. Full article

Powdery mildew fungi are major obligate biotrophic plant pathogens, that cause widespread disease in agricultural and natural ecosystems worldwide, but a comparative structural view of their secretomes across multiple genera has remained limited. Here, we performed computational structure prediction and comparative analysis of 7545 secretome candidates from 26 isolates representing five genera (Blumeria, Erysiphe, Golovinomyces, Parauncinula, and Podosphaera) using AlphaFold2-based structure prediction, structural annotation against CATH, SCOPe, and PDB, Foldseek-based clustering and network analysis, structure-based grouping of RALPH (RNase-like proteins associated with haustoria) candidates, and comparison with defined fungal effector structural families. The predicted secretomes showed comparable model confidence across isolates and revealed a conserved structural core composed of recurrent microbial ribonuclease, immunoglobulin/fibronectin-like, glycosidase-related, and other enzyme-associated folds, with MoHrip2-like representing the most prominent shared fold among defined fungal effector structural families. Structural clustering and network analysis identified a prominent RALPH-centered component with additional conserved and lineage-enriched communities. RALPH candidates formed a structurally diverse repertoire that could be partitioned into 15 topology-defined groups, several linked to previously characterized powdery mildew effectors. Blumeria was structurally distinct, showing expansion of RALPH-associated components and the absence of multiple fold/domain categories retained in dicot-associated genera. Together, these results establish a comparative structural landscape of powdery mildew secretomes and provide a framework for future functional, evolutionary, and genomics-driven studies of conserved and lineage-associated secretome candidate. Full article

Ginger (Zingiber officinale Roscoe) is a high-value horticultural crop widely cultivated for its culinary and medicinal applications, yet its production is increasingly constrained by soil-borne diseases. Among these, Fusarium yellows, caused by Fusarium oxysporum f. sp. zingiberi (Foz), is one of the most damaging constraints in ginger-growing regions around the world, leading to progressive yellowing, vascular blockage, and decline in rhizome quality. Members of the Fusarium oxysporum species complex are known to include both pathogenic and non-pathogenic lineages that often co-occur within the same host and environment, complicating disease diagnosis and epidemiological understanding. In this study, we examined Fusarium-like isolates recovered from both symptomatic and symptomless ginger plants within Southeast Queensland, the major ginger production region in Australia. We then investigated the genetic diversity, effector gene content, and pathogenic potential of these isolates. Comparative analyses revealed two genetically and functionally distinct groups: a clonal Foz lineage consistently associated with Fusarium yellows symptoms and characterised by a conserved set of Secreted In Xylem (SIX) effector genes (SIX7, SIX9, SIX10, and SIX12) and a diverse set of F. oxysporum isolates lacking these effectors. The conserved presence and co-localisation of SIX7, SIX10, and SIX12 within a 5 kb region on a 1.4 Mb contig in the Foz lineage is consistent with the retention of a stable lineage-specific effector module, likely associated with accessory genomic regions that may contribute to host specificity and pathogenicity in the Fusarium oxysporum species complex. Pathogenicity assays confirmed that only the Foz lineage induced disease, whereas non-Foz isolates caused no visible symptoms despite limited colonisation of host tissues. These findings highlight the coexistence of pathogenic and endophytic Fusarium lineages within ginger production systems and support the use of effector-based markers for improved detection and disease management. Full article

Ubiquitination is a key post-translational modification regulating cellular signaling and innate immunity, and its reversal by deubiquitinases (DUBs) represents a critical mechanism exploited by pathogens for immune evasion. While ovarian tumor (OTU) domain-containing DUBs are well characterized in viral systems, their roles in fungal pathogens remain largely unexplored. In this study, we investigated two putative OTU domain-containing proteins derived from the plant pathogenic fungi Melampsora larici-populina (MlpOTU, EGG09943.1) and Taphrina deformans (TdOTU, CCG84064.1). Recombinant MlpOTU and TdOTU proteins were successfully expressed and purified from E. coli and exhibited high solubility and proper folding. Functional analyses in HEK293T cells demonstrated that both proteins significantly reduce global ubiquitination levels, confirming their deubiquitinase activity in vivo. Despite this shared enzymatic function, the two proteins displayed markedly distinct effects on host immune gene expression. MlpOTU selectively suppressed key antiviral effectors, most notably MX1, suggesting a targeted immune evasion strategy. In contrast, TdOTU induced robust upregulation of multiple immune-related genes, including type I interferons, indicating a divergent role. Neither MlpOTU nor TdOTU triggered robust apoptosis, supporting their role as modulators of host signaling rather than cytotoxic effectors. Collectively, these findings provide the first functional evidence that fungal OTU domain-containing proteins act as active deubiquitinases and reveal distinct strategies by which plant pathogens may manipulate host immune responses. This study establishes fungal OTU domains as promising targets for antifungal intervention and broadens our understanding of cross-kingdom evasion mechanisms. 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

Induced resistance primes host immunity for enhanced protection; however, how pathogens respond to this primed state remains poorly understood. Here, we investigated the molecular responses of the rice blast fungus Magnaporthe oryzae during infection of benzothiadiazole (BTH)-primed rice. Seed priming with BTH conferred long-lasting resistance against M. oryzae at the four-leaf stage. Time-course transcriptomic analyses (12–48 hpi) identified 699 differentially expressed genes (DEGs) in M. oryzae, revealing a distinct temporal transition during infection of BTH-primed rice. The fungal transcriptional response shifted from early growth and environmental sensing to enhanced protein turnover, metabolic repression, energy depletion, and genomic instability, indicating progressive impairment of fungal fitness by host immunity. From these DEGs, eight BTH-suppressed candidate virulence genes (MoBVG1–8) were selected for functional characterization. Gene overexpression analyses showed that two genes, MoBVG2 and MoBVG6, significantly increased pathogenicity on BTH-primed rice, while knockout analyses confirmed that both are required for full pathogenicity on non-primed control plants. MoBVG2 encodes a reactive oxygen species (ROS)-scavenging effector, and MoBVG6 encodes an environmental sensor, highlighting the importance of ROS detoxification and environmental perception for successful host colonization. Functional analyses further revealed that MoBVG2 contribute to vegetative growth, while MoBVG6 is required for proper appressorium development. Together, these findings suggest that BTH-induced resistance restricts blast disease by impairing fungal metabolic fitness and suppressing key virulence genes, providing novel insights into the pathogen-side molecular mechanisms underlying chemically induced resistance in plants. Full article

Fungal endophytes are symbiotic microorganisms that establish strong relationships inside plant tissues, providing potential advantages, especially in grasses, by enhancing tolerance to both abiotic and biotic stresses. This review investigates the molecular mechanisms through which fungal endophytes mediate stress tolerance, targeting host–pathogen interactions. By modulating pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and effector proteins, fungal endophytes may contribute to priming the plant’s immune system, enhancing its resistance to pathogen invasion. Moreover, endophyte colonization regulates core processes such as osmotic regulation, reactive oxygen species (ROS) detoxification, and secondary metabolite biosynthesis that enable plants to tolerate environmental stresses like drought, heat, and salinity. The review highlights the impact of endophytes on immune priming, systemic acquired resistance (SAR), and the regulation of non-coding RNAs that regulate host gene networks associated with stress tolerance. Furthermore, the integration of advanced multi-omics techniques genomics, transcriptomics, proteomics, metabolomics, and fluxomics has revealed emerging insights into the genetic and metabolic pathways driving these symbiotic associations. However, grass-specific molecular datasets remain limited, and the consistency of endophyte-mediated tolerance across host species and environmental conditions is not yet fully resolved. Fungal endophytes increase grass stress resilience through coordinated pathogen recognition, RNA regulation, and metabolic reprogramming while AI-assisted multi-omics approaches are emerging as tools for identifying candidate regulatory networks, although empirical validation in grass–endophyte systems remains limited. Together, these advances highlight the potential for climate-smart and sustainable crop improvement. Future research integrating functional genomics, field validation, and biosafety assessment will be essential for translating endophyte-based strategies into reliable agricultural applications. Full article

Mesenchymal stem/stromal cells (MSCs) are widely recognized as potent modulators of inflammation and immune function in bacterial and viral infections. However, their roles in fungal disease remain comparatively under-defined despite the growing clinical burden of invasive and opportunistic mycoses. This Feature Review synthesizes emerging evidence that MSCs influence antifungal outcomes through two complementary axes: (i) host-directed effects, including modulation of immune responses, particularly macrophage responses, and tissue/barrier conditioning; and (ii) fungus-directed effects (direct antifungal activity mediated by contact-dependent mechanisms and secreted antimicrobial factors). We will summarize how MSCs reshape cytokine and chemokine networks and tune innate immune effector functions, with emphasis on macrophage polarization, pattern-recognition receptor signaling, and downstream phagocytic and fungicidal pathways. In parallel, we will review data suggesting that MSCs can interact more directly with fungal pathogens through sensing, physical engagement, and secretion of antimicrobial mediators while highlighting mechanistic uncertainties and model-dependent limitations. A dedicated section will address MSC-derived secretome products (conditioned media, extracellular vesicles) as a cell-free strategy to enhance antifungal immunity. We will critically evaluate conflicting findings across studies, highlighting that outcomes depend on pathogen and host context. Clarifying these context dependencies is essential to rationally develop MSC or secretome-based interventions that are safe, reproducible, and tailored to specific fungal pathogens and patient populations. Full article

Although bacterial secretion systems (BSSs) are well known to mediate antifungal effects, current evidence remains fragmented, and a framework linking antifungal strategies in bacterial–fungal warfare is still absent. In this context, we survey Type I to XI secretion systems, integrating experimentally validated activities with mechanism-based predictions of antifungal potential. On this basis, we highlight that the antifungal activity of BSSs operates through two different layers: direct fungicidal attack, via effector-mediated disruption of fungal cellular integrity, and ecological competition, through nutrient competition, physical niche occupation, and coordinated population-level activities. Nevertheless, the mechanistic understanding of bacterial antifungal strategies remains limited by simplified experimental models, incomplete effector repertoires, and poorly characterized regulatory networks and environmental cues. Addressing these gaps will require integrated experimental models, advanced high-throughput platforms, and comprehensive multi-omics-guided analyses to elucidate how bacteria suppress fungi and to support future applications. In addition, BSSs represent versatile and programmable platforms for the development of sustainable antifungal interventions in both agricultural and biomedical settings. 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

Fungal endophytes are microorganisms that inhabit plant tissues without causing disease and emerge as critical mediators of plant stress tolerance, nutrient acquisition, and ecosystem resilience under diverse climate change scenarios. Their unique position within the host allows them to modulate physiological responses more closely than external microbiota. This review explores how endophytic fungi contribute to plant adaptation under climate-induced stresses such as heat, salinity, drought, pollution, and nutrient limitation, with a focus on molecular crosstalk, functional trait modules, and metabolic trade-offs. Key findings emphasize multilayered signaling systems, including MAMP/DAMP recognition, phytohormone regulation, immune tuning, ROS dynamics, and effector deployment, while emerging mechanisms such as cross-kingdom RNA and extracellular vesicle (EV)-mediated exchange are discussed as promising but currently limited in empirical validation within many endophytic systems. Endophytes also enhance nutrient exchange through conditional carbon-for-benefit trade and may shape rhizosphere microbiota and soil activities through plant-mediated inputs. Integrative multi-omics approaches provide predominantly correlational insights into the mechanistic basis of these effects, linking molecular function to ecosystem and community outcomes. These insights have potential applications in climate-resilient agriculture, phytoremediation, and ecosystem restoration; however, their large-scale implementation requires further field-based validation and context-specific assessment. Future priorities should focus on trait-based selection, ecological modeling, and biosafety evaluation to translate microbial functions into reliable field-level strategies that support sustainable crop performance under accelerating environmental stress. Full article

The discovery of bidirectional microRNA transfer between two organisms during plant–microbe interactions and the ability of some fungal pathogens to absorb double-stranded RNA (dsRNA) or short interfering RNA (siRNA) from the environment provided an impetus for exploiting this mechanism in plant defense against pathogens. In this study, we investigated the role of conserved wheat microRNAs (miRNAs), miRNA408 and miRNA159, in inducing plant defense responses and suppressing the virulence of the phytopathogenic ascomycete fungus Parastagonospora nodorum, mediated by necrotrophic effectors (NEs) encoded by SnTox genes regulated by fungal transcription factors (TFs). The foliar spraying with in vitro synthesized siRNA408 and siRNA159 duplexes before inoculation with SnTox3-producing P. nodorum isolate increased wheat plant resistance to the SnB isolate and suppressed the pathogen growth and development. Most likely, silencing of the miRNA408 target genes TaCAT-2A, TaCAT-2B, and TaCLP1, and the miRNA159 target gene TaMYB65, led to the induction of a defense response of wheat plants against P. nodorum. This defense response was characterized by a decrease in the catalase activity, accumulation of hydrogen peroxide, activation of the expression of salicylic acid signaling pathway genes (TaWRKY13, TaPR1), and suppression of the expression of ethylene signaling pathway genes (TaEIN3, TaPR3). We demonstrated for the first time the ability of siRNA159 and siRNA408 to penetrate the mycelium of the pathogen P. nodorum and be involved in the cross-kingdom regulation of fungal genes to suppress the expression of some genes of NE (SnToxA, SnTox3) and fungal TFs (SnStuA). We predicted potential targets for wheat miRNA408 and miRNA159 in the P. nodorum transcriptome, making spray-induced gene silencing (SIGS) promising for use against this pathogen. These results provide valuable insights for studying the cross-kingdom transfer of plant miRNAs. Full article

Aspergillus westerdijkiae is a common pathogenic fungus responsible for postharvest fruit rot in pears, causing substantial economic losses. This fungus also produces ochratoxin A (OTA), which poses serious health risks to humans. During host colonization, fungal pathogens secrete effectors to facilitate invasion. Under host-mimicking culture conditions, transcriptomic analysis of A. westerdijkiae at 24 and 72 h post-inoculation (hpi), combined with signal peptide prediction, identified 272 and 214 up-regulated secreted protein-encoding genes, respectively. Among these, a carboxylesterase gene, AwCES, was found to be significantly up-regulated. Compared to the wild-type strain, deletion of AwCES resulted in reduced conidial production and germination rate. Further studies revealed that the deletion mutant showed significantly attenuated virulence on pear fruit. Moreover, the loss of AwCES impaired fungal adaptation to stress environments. Collectively, these findings demonstrate that AwCES plays a critical role in the growth, development, and pathogenicity of A. westerdijkiae. Full article

The pressing need for sustainable, plant-based alternatives is highlighted by the growing resistance of agricultural pests to synthetic pesticides. This study examined the pesticidal potential of phytocompounds from C. tora discovered by GC–MS analysis against important tomato insect (T. absoluta) and fungal pathogen (A. solani). The binding stability and interaction dynamics of specific metabolites with fungal virulence (polygalacturonase, MAP kinase HOG1, and effector AsCEP50) and insect neuromuscular (ryanodine receptor and sodium channel protein) targets were assessed using molecular docking and 100 ns molecular dynamics simulations. Among the screened compounds, squalene and 4,7,10,13,16,19-docosahexaenoic acid, methyl ester (DHAME) exhibited the strongest binding affinities and conformational stability, with MM-GBSA binding free energies of −38.09 kcal·mol⁻¹ and −52.81 kcal·mol⁻¹ for squalene complexes in T. absoluta and A. solani, respectively. Persistent hydrophobic and mixed hydrophobic–polar contacts that stabilised active-site residues and limited protein flexibility were found by ProLIF analysis. These lively and dynamic profiles imply that DHAME and squalene may interfere with calcium signalling and stress-response pathways, which are essential for the survival and pathogenicity of pests. Hydrophobic interactions were further confirmed as the primary stabilising force by the preponderance of van der Waals and nonpolar solvation energies. The findings show that C. tora metabolites, especially squalene and DHAME, are promising environmentally friendly biopesticide candidates that have both insecticidal and antifungal properties. Their development as sustainable substitutes in integrated pest management systems are supported by their stability, binding efficacy and predicted biosafety. Full article

Hibernation profoundly alters host–pathogen dynamics by suppressing metabolism and immune function, posing unique challenges for infection control. In this study, we examined how genomic variation modulates infection and physiological traits in temperate bats during hibernation. We combined infection screening, haematology, blood biochemistry, and whole-genome sequencing across five vespertilionid species, identifying over 170,000 single nucleotide variants (SNVs) and assessing their associations with 23 health-related variables. Using the phylogenetically informed treeWAS framework, we detected 515 significant SNVs linked to traits including fungal, protozoan and bacterial infections, acid–base balance, and blood cell indices. These SNVs mapped to 137 unique genes, which were enriched for functional domains related to cytoskeletal dynamics, membrane trafficking, and intracellular signalling (e.g., SH3, C2, BAR, semaphorin). Notably, canonical immune effector genes were underrepresented, and several trait-associated SNVs appeared in blocks across multiple scaffolds, pointing to regulatory loci as key modulators of hibernator health. Our findings support the hypothesis that bats rely on infection tolerance rather than resistance during hibernation, with genomic variation in regulatory and signalling pathways shaping their physiological responses to infection under energy-limited conditions. Full article