Virulence最新文献

Cystatin B (CSTB) is an endogenous cysteine protease inhibitor that plays a critical role in the modulation of numerous biological processes, involving immune responses, apoptosis, and inflammation in mammals. However, its immunological functions in teleost, particularly Nile tilapia (Oreochromis niloticus) remain unclear. In the present study, the CSTB was cloned and characterized from Nile tilapia (On-CSTB) and its role in bacterial infection was revealed. The On-CSTB open reading frame is 300 bp encoding 99 amino acids that contains a conserved cystatin domain. Multiple sequence alignment analysis revealed that On-CSTB share over 75% identity with fish lineages, and 45% identity with mammals. qPCR analysis showed that On-CSTB is widely expressed across various tissues and highly expressed in blood cells and intestines and can be significantly inducted by Streptococcus agalactiae (S. agalactiae) and Aeromonas hydrophila (A. hydrophila). In vivo experiments demonstrated that On-CSTB protein could suppress inflammation while participating in the MyD88/NF-κB signaling pathway and inflammasome activation, affecting apoptosis and pyroptosis processes. Moreover, On-CSTB contributed to enhanced tissue integrity and alleviated pathological damage. These findings collectively highlight On-CSTB as a crucial immunomodulator that contributes to host defense and tissue protection in fish. The present study offers novel perspectives on the immunomodulatory role of CSTB in tilapia, providing a basis for disease resistance strategies in aquaculture.

Staphylococcus aureus, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, S. aureus exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies - including biofilm formation, small colony variants, and inhibition of phagolysosomal killing - further enhance persistence and immune evasion. While these mechanisms are well studied in extracellular infections, their role in intracellular survival is increasingly evident. This review synthesizes emerging insights into how S. aureus manipulates macrophage function to establish chronic bone infection and highlights therapeutic opportunities targeting macrophage polarization to improve immune-mediated clearance and bone repair in osteomyelitis.

Vacuoles are essential organelles in eukaryotic cells, playing key roles in cellular homeostasis through nutrient sensing, osmoregulation, and autophagy. In filamentous fungi, vacuole dynamics are crucial for mycelial growth, stress response, and pathogenicity. The vacuolar functions and their regulation in nematode-trapping (NT) fungi remain poorly understood. Here, we characterized a vacuolar protein sorting (Vps) protein Vps18 (AoVps18) in a typical NT fungus Arthrobotrys oligospora, which is required for the proper regulation of mycelial growth, trap formation, and sporulation. Through integrated phenotypic and molecular analyses, we established that AoVps18 physically interacts with core mitogen-activated protein kinase (MAPK) signaling components (AoSte12 and AoFus3) to coordinate predation-related cellular processes, including vacuole assembly, mitochondrial dynamics, and lipid droplet accumulation. Notably, we identified a TGAAAC regulatory motif in the Aovps18 promoter, suggesting direct transcriptional control by the MAPK effector, AoSte12. RNA sequencing and metabolomics further revealed that AoVps18 is involved in regulating multiple cellular processes and synthesizing compounds critical for the chemotaxis of nematodes toward A. oligospora. Overall, these findings elucidate the regulatory mechanisms by which AoVps18 coordinates vacuolar function with trap morphogenesis and mycelial growth in NT fungi, advancing both the fundamental understanding of Vps proteins regulation and potential biocontrol applications against plant-parasitic nematodes.

The non-structural protein (Npro) of bovine viral diarrhea virus (BVDV) is a crucial virulence factor that impairs the host's antiviral immune response and facilitates virus production. This study establishes a foundation for understanding how different selective pressures influence the formation of nucleotide pairs, synonymous codon, and context-dependent codon bias (CDCB) in BVDV Npro. BVDV genotype 1 exhibits a greater number of subgenotypes compared to other genotypes, yet its overall nucleotide usage bias in Npro is stronger. Within Npro, certain dinucleotides, specifically CpG and UpA, are notably suppressed, while UpG is selected with high frequency across all genotypes. The BVDV Npro region exhibits a pronounced bias in synonymous codon usage and possesses a genetic capacity to distinguish between genotypes. Unlike the patterns of mononucleotide and synonymous codon usage associated with BVDV genotyping, nucleotide pair usage and CDCB show significant variability due to the high mutation rate in the Npro coding sequence. Despite this variation, both nucleotide architectures demonstrate a unique evolutionary paradigm that goes beyond genotype-specific models. Aside from nucleotide composition constraints imposed by the high mutation rate in the viral genome, natural selective pressures arising from translational selection and host immune response also significantly influence the formation of various nucleotide architectures in the BVDV Npro. By analyzing the genetic characterizations associated with the different nucleotide architectures in the Npro, the diverse repertoire of nucleotide pairs, synonymous codons and CDCB may provide BVDV mutants with ample opportunities for direct adaptation and exaptation, thereby overcoming the robust immune defenses of the host.

Candida species are major contributors to nosocomial infections, with biofilm formation being a critical virulence factor that enables persistence in clinical settings and resistance to antifungal therapies. Central to biofilm development is the adhesion of fungal cells, a process mediated by surface proteins such as Als5p in Candida albicans. The amyloid-forming peptide sequence within Als5p (³²²SNGIVIVATTRTV³³⁴) has been implicated in mediating adhesion and biofilm formation; however, its role in shaping the biofilm architecture has not been fully elucidated. In this study, we demonstrated that the addition of Als5pFP promoted biomass accumulation in C. albicans biofilms under laboratory conditions, including complex media and at temperatures compatible with clinical biofilm assays. Using advanced image analysis of microscopy images, we show that the Als5p peptide induces a distinct morphological effect on biofilms: a shape-edging of microcolony structures, characterized by the concentration of fungal cells into denser aggregates and the reduction of cells in intermediate spaces. These observations suggest a potential role of amyloid-like fibrils formed by the Als5p peptide in influencing the spatial organization of C. albicans biofilms. This discovery presents a novel aspect on how these fibrils affect the biofilm architecture extending beyond previous studies, which primarily focused on biomass accumulation. Our findings contribute to the understanding of the architectural development of C. albicans biofilms and provide a foundation for future research aimed at targeting the amyloid structures within fungal biofilms. Furthermore, the results may support the design of biofilm-targeting antifungal agents and development of biosensors for monitoring amyloid formation during infection.

Ketone volatile organic compounds have demonstrated favorable inhibitory activity against a wide range of pathogenic fungi, including Pseudogymnoascus destructans (Pd), the lethal pathogenic fungus responsible for white-nose syndrome in bats. However, the mechanism of fungal inhibition by ketones remains unclear. In this study, we employed transcriptomic analysis to conduct RNA sequencing on Pd treated with 2-undecanone and 2-nonanone, aiming to investigate the effects of these ketones on the gene expression profiles of Pd. The results indicated that 2-undecanone and 2-nonanone inhibit spore germination in Pd and cause significant damage to its mycelium. The minimum inhibitory concentrations (MIC) were determined to be 25.94 μg/mL and 135.41 μg/mL, respectively. Transcriptomic analysis revealed these ketones affects Pd through multiple pathways, inducing lesions in the cell wall and membrane, and disrupting ribosomal stability by interfering with rRNA modifications and ribosome assembly. Additionally, we found that 2-undecanone impacts enzymes involved in the tricarboxylic acid cycle, disrupting energy metabolism by interfering with critical metabolic pathways in aerobic organisms. In contrast, 2-nonanone directly damages Pd DNA, triggering the activation of DNA damage repair mechanisms. This study provides a theoretical basis for exploring novel antifungal strategies targeting Pd, suggesting that ketones may serve as potential in vitro defense and control tools, laying the groundwork for the subsequent development of efficient fumigants.

H11 subtype avian influenza viruses (AIVs) have been identified in both wild and domestic birds. H11N9 viruses from wild birds provided the NA gene to human H7N9 virus in 2013 in China, which caused five waves of human infections. During active surveillance in wild birds in China, 17 H11 viruses were isolated between December 2022 and January 2024, including six H11N1, one H11N2, one H11N3, and nine H11N9. The epidemiology of H11 subtype viruses in public databases revealed that they distributed across seven continents, and more than 54.9% of H11 viruses originated from wild Anseriformes. Phylogenetic analysis of the HA genes indicated that H11 viruses were classified into Eurasian and North American lineages, and our isolates belonged to the Eurasian lineage. Bayesian phylogeographic analysis suggested that Bangladesh served as a crucial geographical transmission center for H11 viruses in Eurasian lineage. Reassortment indicated that the H11 isolates in the study underwent complex genomic recombination with various subtype AIVs circulating in wild and domestic birds, including the clade 2.3.4.4b H5N1 highly pathogenic viruses, and formed seven genotypes. Notably, 17 H11 isolates acquired several mutations associated with enhanced human-type receptor binding in HA (S137A) and increased mammalian virulence in PB1 (D3V, D622G), PB1-F2 (N66S), M1 (N30D, I43M, T215A), and NS1 (P42S, I106M). Seven representative viruses exhibited dual receptor binding specificity and could infect mice directly without prior adaptation. These findings highlight the potential public health risks posed by H11 viruses from wild birds and emphasize the necessity of enhancing routine surveillance.

Orthobunyaviruses, including La Crosse virus (LACV), Oropouche virus (OROV), Schmallenberg virus (SBV), and Akabane virus (AKAV), pose substantial threats to global public health and livestock industries. This review focuses on the interplay between these viruses and the host immune systems, highlighting key mechanisms of viral entry and immune evasion. The viruses exploit vulnerabilities in host innate immunity, particularly through nonstructural protein NSs, which disrupts type I interferon signaling and transcriptional machinery. Additionally, this review delineates how host restriction factors counteract viral proliferation through compartmentalized defense mechanisms including BST-2 and MxA. The review also discusses antiviral strategies, including vaccines and inhibitors. Hence, this review synthesizes current knowledge on host recognition, immune evasion, and therapies for Orthobunyaviruses infections (focusing on LACV, OROV, AKAV, SBV) to guide targeted antiviral and broad-spectrum countermeasure development against emerging Orthobunyaviruses threats.

Hepatitis B virus (HBV) is increasingly recognized for its involvement in extrahepatic diseases, including rheumatological manifestations such as arthritis and joint pain. This review introduces the concept of the liver-joint axis, hypothesizing that HBV may contribute to rheumatoid arthritis (RA) pathogenesis through immune and metabolic dysregulation. We emphasize the effect of HBV infection on fibroblast activation, metabolic reprogramming, and Th17/Treg imbalance. Transcriptome analysis further elucidates the complex signaling networks underlying HBV-associated RA. These findings support a pathogenic role for HBV in joint inflammation and suggest novel therapeutic opportunities for targeting HBV-driven RA.

Staphylococcus aureus is a major human opportunistic pathogen that causes significant morbidity and mortality, particularly in immunocompromised individuals. SaeRS is a two-component system in S. aureus that regulates signal transduction related to virulence, including hemolysis and coagulation. Metal ions are essential nutrients that support bacterial virulence and survival against host immune cells and are intricately interconnected with regulatory systems. The SaeRS system has long been studied for its function in bacterial virulence and invasive infections. However, its interactions with other regulators and metal ions remain unelucidated. Thus, this study evaluated the effects of the S. aureus SaeRS system on virulence, specifically its association with oxidative stress resistance and staphyloxanthin (STX) production. saeS deletion reduced STX production via the SigB-CrtOPQMN pathway, increasing vulnerability to oxidative stress and susceptibility to host immune cells. Supplementation with metal ions, specifically zinc, inhibited STX-associated gene expression, attenuating antioxidative activity in vitro. Experiments on mice with S. aureus bloodstream infection verified that SaeS was crucial for bacterial survival in vivo. Furthermore, zinc contributed to weakened bacterial virulence and altered host immune defense mechanisms. Collectively, our results established a novel mechanistic interconnection between SaeRS and STX biosynthesis and demonstrated that SaeRS inhibition combined with zinc supplementation promotes innate immune system-mediated killing of S. aureus.