K39 , a previously unrecognized hypervirulent serotype, was isolated from a septicemic neonate. It was assessed for the acquisition of hypervirulence determinants and virulence potential. Transmissibility of plasmids, fu...K39 , a previously unrecognized hypervirulent serotype, was isolated from a septicemic neonate. It was assessed for the acquisition of hypervirulence determinants and virulence potential. Transmissibility of plasmids, functional expression of virulence determinants, capsule visualization (TEM), comparative genome analysis and virulence potential ( , assays) were studied. Carbapenem-resistant ST985-K39 (Sil80), harbored , , , , in IncFIB(K)/IncHI1B(pNDM-MAR) hypervirulent plasmid; in IncFIB(pQIL)/IncFII(K) plasmid and other antimicrobial resistance determinants in IncFII plasmid. Comparative genomic analysis of global K39 isolates revealed, for the first time, the acquisition of a hypervirulent plasmid in the K39 study isolate. IncFIB(pQil)/IncFII(K) carrying showed successful conjugation independently. However, hypervirulent plasmid [IncFIB(K)/IncHI1B(pNDM-MAR)] could not successfully transmit alone, but was co-transmitted along with IncFII plasmid, because of site similarity. The strain was serum-resistant and produced a strong biofilm. Despite possessing hypervirulence determinants, Sil80 showed a negative string test, a thin capsule, and attenuated virulence in adult mice. Deletion of 10 amino acids in RmpD and mutation in promoter having 10T track (P) were observed. Expression of , , and in Sil80 was also downregulated. Mutations in the promoter and truncated RmpD of Sil80 caused attenuated virulence in adult mice; nonetheless, the isolate was capable of causing sepsis in an immunocompromised neonate. The transfer of the non self-conjugative virulence plasmid was facilitated by the helper plasmid with a similar site. This phenomenon could facilitate the spread of such plasmids to hitherto unknown serotypes.
Sepsis is a life-threatening condition characterized by dysregulated host responses to infection and remains a leading cause of mortality globally. While host inflammatory pathways have been extensively studied, the cont...Sepsis is a life-threatening condition characterized by dysregulated host responses to infection and remains a leading cause of mortality globally. While host inflammatory pathways have been extensively studied, the contribution of bacterial proteases to sepsis pathogenesis remains underappreciated. Emerging evidence indicates that bacterial proteases act as potent virulence factors that directly target the vascular endothelium by cleaving junctional proteins, degrading the glycocalyx, inactivating anticoagulant molecules and degrading key coagulation factors such as fibrinogen, factor V, factor VIII and thrombin. This combined structural and functional damage leads to endothelial barrier failure, vascular leakage and progression toward disseminated intravascular coagulation (DIC). Additionally, bacterial proteases increase inflammatory cytokine release, degrade complement components and drive thrombo-inflammatory dysregulation. This review summarizes mechanistic insights into key microbial proteases such as EspP, Protease IV, LasB and SpeB, highlighting experimental models, diagnostic challenges and emerging protease-targeted therapeutic strategies with implications for improving sepsis outcomes.
Due to the increasing global antibiotic resistance spread, novel antibacterial strategies targeting virulence factors instead of bacterial growth are clinically crucial. One promising approach involves interfering with b...Due to the increasing global antibiotic resistance spread, novel antibacterial strategies targeting virulence factors instead of bacterial growth are clinically crucial. One promising approach involves interfering with bacterial quorum-sensing systems, which regulate virulence and enhance adaptability. To this end, exploring quorum sensing inhibitors from Chinese medicine monomers have gained attention. The key quorum-sensing systems of (, , and ) control multiple virulence factors and contribute to pathogenicity. This study screened a library of Chinese medicine monomers by constructing a '- fusion reporter system and first discovered that α-mangostin can act as a novel inhibitor of the system in . Subsequent experiments demonstrated that α-mangostin can effectively inhibit the system and associated virulence phenotypes, including biofilm formation, motility (swarming, swimming, and twitching), and the production of virulence factors (pyocyanin, hydrogen cyanide, elastase, and lectin), without affecting bacterial growth. Moreover, both genetic complementation assays and molecular docking analyses indicated that α-mangostin inhibits the system by targeting the PqsR protein. Site-directed mutagenesis, circular dichroism spectroscopy, and isothermal titration calorimetry confirmed that PqsR is the direct target of α-mangostin and that the alanine residue at position 168 of PqsR is the key bindingsite. Finally, α-mangostin effectively attenuated virulence in Chinese cabbage () and bacterial adhesion to and invasion of human lung epithelial A549 cells. In summary, α-mangostin effectively inhibits virulence without affecting its growth by targeting its system, providing a new strategy for the prevention and treatment of infections.
The stable structure of biofilms and the characteristics of the bacteria within them make biofilms an important barrier for bacteria to resist external stress, and a key factor contributing to the difficulty of eradicati...The stable structure of biofilms and the characteristics of the bacteria within them make biofilms an important barrier for bacteria to resist external stress, and a key factor contributing to the difficulty of eradicating clinical infections. This article reviews the multi-stage formation process of biofilms, the various mechanisms of antibiotic tolerance and resistance (such as physical barriers, metabolic adaptations, horizontal gene transfer, etc.), as well as the integrated regulatory roles of molecular networks like quorum sensing (QS) and cyclic diguanosine monophosphate (c-di-GMP). These multiple protective mechanisms in biofilms compose a closed "structure-function" loop system. In the past few years, the emergence of new anti-biofilm intervention approaches (matrix-degrading enzymes, phage therapy, nanomaterials, gene editing, etc.) revealed the possibility to break the limitations of conventional antibiotics by compromising structural integrity or interfering with signaling pathways, providing new ideas for drug-resistance infection control.
Unlike vertebrates, which use adaptive immunity, insects depend on humoral and cellular innate immunity to resist pathogens, with pattern recognition receptors (PRRs) like C-type lectins (CTLs) critical for recognizing p...Unlike vertebrates, which use adaptive immunity, insects depend on humoral and cellular innate immunity to resist pathogens, with pattern recognition receptors (PRRs) like C-type lectins (CTLs) critical for recognizing pathogen-associated molecular patterns (PAMPs). CTLs are a diverse, mostly Ca-dependent glycoprotein superfamily defined by conserved Carbohydrate Recognition Domains (CRDs), enabling ligand binding and mediating immune defenses in invertebrates. , a vital pollinator, faces severe threats from pathogens such as , a major cause of nosemosis that damages midguts, reduces vitality, and triggers colony collapse. This highlights the urgency of studying bee immune mechanisms. Here, we identified AcCTL5 (a CTL from ), prepared, purified its recombinant protein, and characterized its functions. Recombinant AcCTL5 strongly agglutinated , bound significantly to PAMPs (galactose, peptidoglycan, lipoteichoic acid, lipopolysaccharide), reduced honeybee infection rates, and participated in prophenoloxidase activation and hemolymph melanization. These results suggested that may play an important role in the immune defense response of against , and lay the foundation for further research on the molecular mechanism of involved in the innate immunity of .
Getah virus (GETV), a mosquito-borne arbovirus of the Alphavirus genus, poses an emerging threat to livestock economies and public health, underscored by its expanding host range and association with recent outbreaks of...Getah virus (GETV), a mosquito-borne arbovirus of the Alphavirus genus, poses an emerging threat to livestock economies and public health, underscored by its expanding host range and association with recent outbreaks of heightened virulence. While the functional significance of the 3' untranslated region (3'UTR) in alphavirus biology is recognized, its specific role in GETV remained undefined. Herein, we elucidate the virological functions of the GETV 3'UTR through a reverse genetics approach, generating a panel of viruses with targeted deletions. We demonstrate that the GETV 3'UTR is remarkably plastic, tolerating a consecutive deletion of up to 310 nucleotides while remaining viable. Deletion of conserved repeat sequence elements (RSEs) induced a cell-type-specific replication deficiency in vitro and significantly attenuated virulence in a murine model. A comprehensive deletion mutant (rGETV-KO310) exhibited further impaired replication kinetics in vitro and was profoundly attenuated in vivo, eliciting only transient morbidity with no mortality in both neonatal and weaned mice. Furthermore, this mutant displayed a significant defect in early colonization within mosquito vectors, indicating a role in vector competence. Comparative transcriptomic profiling of knee joints revealed that attenuation correlates with the altered modulation of critical host immune responses, notably the interferon and MAPK signaling pathways. Collectively, these findings establish the GETV 3'UTR as a pivotal regulator of viral fitness, pathogenesis, and transmission. This work provides a foundational rationale for the strategic development of live-attenuated vaccine candidates based on targeted 3'UTR attenuation.
(Mhp), the causative agent of swine enzootic pneumonia, has been linked to hepatic dysfunction, however, the underlying metabolic mechanisms remain unclear. We established an Mhp infection model and investigated hepatic...(Mhp), the causative agent of swine enzootic pneumonia, has been linked to hepatic dysfunction, however, the underlying metabolic mechanisms remain unclear. We established an Mhp infection model and investigated hepatic responses by integrating transcriptomic and metabolomic analyses. Liver dysfunction was evaluated histologically via H&E staining and serum biochemistry. Mhp infection caused hepatic injury characterized by elevated serum aspartate aminotransferase (AST), triglyceride (TG) accumulation, increased non-esterified fatty acids (NEFAs), and neutrophil infiltration. A total of 3,241 differentially expressed genes and 685 metabolites were identified and were enriched in PPAR signaling, inflammatory, and energy metabolism pathways. Genes related to fatty acid oxidation, antioxidation, and energy metabolism were downregulated, whereas those associated with TG synthesis and inflammation were upregulated. Reduced cyclic adenosine monophosphate (cAMP) levels, decreased superoxide dismutase (SOD) activity, and elevated hydrogen peroxide (HO) and malondialdehyde (MDA) indicated oxidative stress and impaired energy production. These findings provide mechanistic insights into Mhp-induced hepatic metabolic injury and potential therapeutic targets.
An overactivated cytokine storm during the early phase of sepsis is associated with increased mortality. Although various cytokine-targeting therapeutic strategies have been evaluated in clinical trials, their efficacy r...An overactivated cytokine storm during the early phase of sepsis is associated with increased mortality. Although various cytokine-targeting therapeutic strategies have been evaluated in clinical trials, their efficacy remains limited. Here, we focus on the previously less studied cytokine interleukin-24 (IL-24) and demonstrate its pathogenic role in ()-induced sepsis. Elevated IL-24 expression was observed in septic wild-type mice. In contrast, IL-24 knockout mice exhibited improved survival, reduced bacterial load, and diminished neutrophil and T-cell infiltration. Both and experiments revealed that recombinant IL-24 protein enhances the bacterial accumulation and leukocyte chemotaxis. Finally, inhibition of IL-24 expression significantly reduced sepsis-associated mortality. These findings suggest that IL-24 contributes to sepsis pathogenesis by promoting bacterial dissemination and inflammatory amplification, and identify IL-24 as a potential therapeutic target for the precise treatment of sepsis.
f. sp. race 4 (4) is a highly virulent pathogen threatening cotton production globally, particularly in the US. This review synthesizes current knowledge of 4 biology, pathogenesis, and genomic features that drive host...f. sp. race 4 (4) is a highly virulent pathogen threatening cotton production globally, particularly in the US. This review synthesizes current knowledge of 4 biology, pathogenesis, and genomic features that drive host specificity and virulence. 4 life cycle, infection mechanisms, environmental factors influencing disease, and host resistance in Pima and Upland cotton varieties are discussed. Genomic resources reveal that 4 genomes are larger and more repeat-rich than those of several other races, although chromosome-scale core versus accessory architecture remains unresolved. Studies have identified candidate race-specific virulence factors, including race-specific SIX effectors and secondary-metabolite genes in 4 and related races. Challenges remain in managing cotton diseases caused by 4 due to its soil persistence and genetic adaptability. Integrated management combining resistant varieties, cultural practices, and precision monitoring ensures sustainable disease control, while advancing knowledge of 4 virulence mechanisms enhances future management strategies through innovative approaches.
Obesity, a global epidemic, drives coronary microvascular dysfunction (CMD), a precursor to cardiovascular disease, via gut microbiota dysbiosis. Clinical evidence shows a 47.7% reduction in coronary flow reserve among o...Obesity, a global epidemic, drives coronary microvascular dysfunction (CMD), a precursor to cardiovascular disease, via gut microbiota dysbiosis. Clinical evidence shows a 47.7% reduction in coronary flow reserve among obese patients, highlighting obesity's pivotal role in CMD pathogenesis. This review elucidates molecular mechanisms linking obesity-induced dysbiosis to CMD, focusing on microbial metabolites: TMAO promotes lipid deposition and inflammation; reduced SCFAs impair endothelial function; bile acids modulate vascular tone via FXR/TGR5; LPS induces metabolic endotoxemia; BCAAs trigger insulin resistance; endogenous ethanol fosters oxidative stress; indole metabolites exert dual vascular effects; ImP and PAGln accelerate atherosclerosis and thrombosis; and HS deficiency and elevated succinate exacerbate remodeling. The gut-heart axis amplifies CMD risk beyond traditional factors. Future multi-omics studies should identify biomarkers and develop targeted therapies, such as metabolite inhibitors and precision nutrition, to mitigate obesity-related CMD and improve outcomes. The Graphical Abstract is presented in Figure 1.[Figure: see text].
Fungal infections represent a significant and growing threat to public health, exacerbated by an expanding population of immunocompromised individuals and the increasing prevalence of resistance to conventional antifunga...Fungal infections represent a significant and growing threat to public health, exacerbated by an expanding population of immunocompromised individuals and the increasing prevalence of resistance to conventional antifungal agents. Drug repurposing offers a strategic and efficient pathway for antifungal discovery, leveraging existing pharmacotherapies to reduce development costs and mitigate safety risks. This study evaluated the antifungal potential of pinaverium bromide, an FDA-approved antispasmodic drug for functional gastrointestinal disorders, against the prevalent pathogen Candida albicans. Our in vitro analyses revealed that pinaverium bromide demonstrated standalone antifungal activity and acted synergistically with amphotericin B or azole drugs. Moreover, it effectively attenuated key virulence factors of C. albicans, including hyphal formation and biofilm development. The therapeutic efficacy of both monotherapy and combination therapy with amphotericin B or voriconazole was validated in two murine models of systemic candidiasis. Mechanistically, pinaverium bromide disrupted mitochondrial function, induced apoptotic cell death, and impaired iron homeostasis in C. albicans. When combined with amphotericin B, it potentiated the drug's effect by amplifying reactive oxygen species accumulation and enhancing membrane permeabilization. These findings support the potential of pinaverium bromide as a novel antifungal agent, either when used alone or in combination with established antifungal therapies.
BK polyomavirus (BKPyV) persists in the renourinary tract of most adults and can replicate under immunosuppression. In kidney transplant recipients (KTR), it may cause BKPyV-associated nephropathy (BKPyVAN), while in hem...BK polyomavirus (BKPyV) persists in the renourinary tract of most adults and can replicate under immunosuppression. In kidney transplant recipients (KTR), it may cause BKPyV-associated nephropathy (BKPyVAN), while in hematopoietic stem cell transplant recipients (HSCT), it is more often linked to hemorrhagic cystitis (HC). These clinical differences are generally attributed to the type of graft and immunosuppressive regimen. However, viral factors such as genotype or mutations might also influence tissue tropism and pathogenesis. This study aimed to compare the virological features of BKPyV between KTR and HSCT recipients and to explore possible associations with clinical manifestations. This retrospective study included 101 transplanted patients (66 KTR, 35 HSCT) at Amiens-Picardie University Hospital (France) between 2019 and 2023, with at least one episode of BKPyV DNAuria during post-allograft follow-up. Viral genotyping was performed by Sanger sequencing, while NGS (Next-generation Sequencing) provided complete coding genome sequences for 51 patients. Genotype distribution was similar in both groups, with Ib2 as the most frequent subtype. No genotype or mutation was associated with a specific graft type or complication, except for the small t antigen gene, which appeared to be more frequently mutated in KTRs. Viral replication occurred earlier and at higher levels in HSCT patients (mean peak DNAuria: 9.3 log vs 7.4 log copies/mL in KTR; < 0.0001). In KTRs, patients with presumptive BKPyVAN were significantly older than those with asymptomatic replication. These findings suggest that viral genetic determinants play a lesser role in BKPyV replication and its clinical consequences compared to host-related factors.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing acute fever, rashes, and even acute or chronic arthralgia/arthritis. With its expanding global distribution, CHIKV represents a significant public health t...Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing acute fever, rashes, and even acute or chronic arthralgia/arthritis. With its expanding global distribution, CHIKV represents a significant public health threat, yet no specific antivirals are approved. The lifecycle of CHIKV is highly dependent on interactions with host factors that mediate viral entry, genome replication, protein translation, assembly, and release. A deeper understanding of these host factors provides new insights into CHIKV pathogenesis and offers strategies to overcome drug resistance associated with high viral mutation rates. This review summarizes and updates current knowledge on the roles of host factors in CHIKV infection, systematically dissects the interaction network and cell-type specificity of key host factors, critically evaluates the druggability of host-directed therapeutic targets, and outlines recent progress in anti-CHIKV drug development, with a focus on strategies targeting both viral proteins and host dependencies, placing a particular emphasis on host-directed antiviral therapies.
Nasopharyngeal carcinoma (NPC) is an Epstein - Barr virus (EBV)-associated epithelial malignancy characterized by an immune-rich yet immunosuppressive microenvironment. EBV establishes an inflammatory but immune-tolerant...Nasopharyngeal carcinoma (NPC) is an Epstein - Barr virus (EBV)-associated epithelial malignancy characterized by an immune-rich yet immunosuppressive microenvironment. EBV establishes an inflammatory but immune-tolerant ecosystem that underlies poor responses to immunotherapy. While prior studies have focused on single checkpoints such as PD-1/PD-L1, they often overlook the systemic immune reprogramming driven by EBV. Viral latent proteins, particularly LMP1, activate NF-κB and JAK - STAT signaling, inducing cytokine production, immune cell reeducation, and therapeutic resistance. This leads to upregulation of multiple checkpoint molecules, T-cell dysfunction, myeloid suppression, and immune exclusion. Consequently, anti-PD-1 therapies show limited efficacy, as tumors exploit alternative checkpoints (e.g. TIM-3, LAG-3, TIGIT) and stromal barriers. This review comprehensively summarizes EBV-driven immune remodeling in NPC and highlights emerging therapeutic strategies targeting both host immunity and EBV-associated signaling axes to overcome immune escape, enhance immunotherapy efficacy, and ultimately improve clinical outcomes.
Colorectal cancer (CRC) is linked to gut microecological imbalances, and increasing evidence suggests that oral-gut microecosystem aberrant interactions also significantly contribute to CRC pathogenesis. The emerging "or...Colorectal cancer (CRC) is linked to gut microecological imbalances, and increasing evidence suggests that oral-gut microecosystem aberrant interactions also significantly contribute to CRC pathogenesis. The emerging "oral-gut axis" offers novel perspectives into the cross-organ microbial regulation. Notably, the oral bacterium exhibits spatiotemporal specificity during CRC progression and may modulate gut microecology and CRC via this axis. This review examines the oral-gut microecological interplay and teases apart the multidimensional associations between (e.g. , ) and CRC, including their heterogeneity across CRC patient groups and their dynamic evolution and spatial distribution during the "adenoma-carcinoma" sequence. It summarizes mechanisms whereby influences CRC by promoting tumor cell proliferation, inducing epithelial-mesenchymal transition, and reshaping the tumor microenvironment. It also categorizes the key technologies in this field. Furthermore, this review highlights potential as a CRC biomarker and therapeutic target, proposing future intervention strategies targeting oral-derived microbes to stimulate further research.
(pneumococcus) remains a significant cause of pneumonia, bacteremia, sepsis, meningitis, and otitis media. The ability of pneumococcus to enter a state of genetic competence is central to pneumococcal adaptability and vi...(pneumococcus) remains a significant cause of pneumonia, bacteremia, sepsis, meningitis, and otitis media. The ability of pneumococcus to enter a state of genetic competence is central to pneumococcal adaptability and virulence. Activation of the competence state enables pneumococcus to uptake exogenous DNA for genetic transformation, acquire genome plasticity and antimicrobial resistance, while also regulating stress tolerance, biofilm formation, and coordinated expression of virulence factors. This review summarizes current evidence on competence-regulated virulence across diverse infection models, including nasopharyngeal colonization, otitis media, meningitis, bacteremia, and pneumonia, highlighting how the competence regulon impacts pneumococcal host colonization, invasion, and disease progression. Comparative insights into pneumococcal competence versus are provided to highlight context-dependent regulation of disease progression. Finally, this review examines emerging competence regulon-targeted therapeutic strategies, including dominant-negative competence-stimulating peptides and inhibitors of competence induction, which have been shown to suppress transformation and attenuate pneumococcal virulence.
Encephalomyocarditis virus (EMCV), an important zoonotic pathogen, causes an acute disease characterized primarily by encephalitis and myocarditis. Interferon (IFN) activates the JAK-STAT signaling pathway to induce the...Encephalomyocarditis virus (EMCV), an important zoonotic pathogen, causes an acute disease characterized primarily by encephalitis and myocarditis. Interferon (IFN) activates the JAK-STAT signaling pathway to induce the expression of interferon-stimulated genes (ISGs), resulting in antiviral effects. However, the mechanism through which EMCV evades the immune system via the IFN-mediated JAK-STAT signaling pathway remains poorly understood. Here, we identified an E3 ubiquitin ligase, RNF149, that is upregulated in EMCV-infected cells. Overexpression of RNF149 inhibited type I IFN-mediated JAK-STAT signaling pathway activation and its antiviral response, enhancing viral replication. Knockout of RNF149 promoted ISGs expression. Notably, RNF149 interacted with JAK1 and downregulated its protein expression through the E3 ubiquitin ligase. RNF149 promoted the K27- and K33-linked ubiquitination of JAK1, which promoted JAK1 degradation through the proteasome pathway. Taken together, these data describe a negative regulatory mechanism involving RNF149 in interferon antiviral activity and provide insights into the mechanism by which EMCV evades host antiviral immunity. These results provide a new strategy for treating viral infections.
Chikungunya virus (CHIKV) poses a major global health challenge. Despite extensive research, effective antiviral treatments remain lacking, underscoring the urgent need for novel therapeutic strategies. The nonstructural...Chikungunya virus (CHIKV) poses a major global health challenge. Despite extensive research, effective antiviral treatments remain lacking, underscoring the urgent need for novel therapeutic strategies. The nonstructural (ns) polyprotein P1234, which is processed into enzymes essential for viral replication and disease progression. This review focuses on nsP2, a multifunctional enzyme possessing cysteine protease, nucleoside triphosphatase (NTPase), RNA helicase, and RNA triphosphatase (RTPase) activities. We summarize current knowledge of nsP2 structure and function and highlight its central roles in viral RNA replication, modulation of host antiviral responses, and immune evasion. Growing evidence identifies nsP2 as a key virulence factor and a promising antiviral target. By integrating recent advances in structural virology and host - pathogen interaction studies, this review provides insights that may guide rational design of nsP2-directed therapeutics. These insights not only deepen our understanding of CHIKV molecular biology but also contribute to broader strategies for combating emerging viral diseases.
is a zoophilic dermatophyte and the primary cause of bovine dermatophytosis, a contagious and economically significant skin disease with zoonotic potential. Despite its importance, high-quality genomic and transcriptomic...is a zoophilic dermatophyte and the primary cause of bovine dermatophytosis, a contagious and economically significant skin disease with zoonotic potential. Despite its importance, high-quality genomic and transcriptomic resources for this species remain scarce, limiting insights into its pathogenic mechanisms and antifungal responses. Here, we present a chromosome-level genome assembly of OR056436.1, generated using single-molecule real-time (SMRT), Illumina paired-end and high-throughput chromosomal conformation capture (Hi-C) technologies, followed by comprehensive annotation and comparative analyses with six other fungal pathogens. Transcriptome profiling under itraconazole (ITR) and Xuanjing - Compound Chinese Herbal Spray (CCM) treatments revealed antifungal-responsive genes. The final 23.44 Mb genome comprises 7,936 protein-coding genes, with 4.98% repetitive sequences, and shows 98.8% completeness based on BUSCO analysis. Functional annotation identified 262 Kyoto Encyclopedia of Genes and Genomes pathways, 4,861 Eukaryotic Orthologous Groups proteins, 34 secondary metabolite biosynthetic gene clusters, 1,157 carbohydrate-active enzymes, 2,920 pathogen-host interaction genes, and 59 virulence factor genes. Comparative genomics identified 45,425 orthogroups including 393 core and 184 single-copy orthogroups, placing . closest to . Transcriptomic analysis highlighted differentially expressed genes enriched in amino acid metabolism, ABC transporters, drug metabolism, and stress response pathways. Notably, subtilisin-like proteases and LysM-domain proteins were significantly regulated under antifungal treatments. This integrative genomic-transcriptomic study provides the most complete genome to date, identifies key genes involved in pathogenicity and antifungal adaptation, and offers valuable resources for diagnostics, therapeutic development, and improved strategies for bovine dermatophytosis.