Microbial pathogenesis最新文献

Salmonella infections remain a major public health challenge, and innovative probiotic strategies are urgently needed. This study investigates the protective effects of a kefir grain and beverage mixture against Salmonella Typhimurium infection in rats. Thirty-six male Sprague-Dawley rats were allocated to three groups: (1) control (no kefir or Salmonella), (2) kefir + Salmonella (Sal) receiving daily kefir grain/beverage for four weeks, and (3) Salmonella-only (no kefir). On day 21, both kefir-treated and Salmonella groups were challenged with S. Typhimurium 14028. Results showed that kefir treatment markedly lowered Salmonella levels in the liver, spleen, feces, and cecal contents. Liver enzymes activity and inflammatory markers- Interleukin 10, serum amyloid A, and tumor necrosis factor α-were lower in the kefir treated group relative to the Salmonella group, indicating reduced hepatic injury and systemic inflammation. Kefir consumption also mitigated the infection-induced rise in white blood cell counts, implying an overall suppression of the inflammatory response. Collectively, the findings support the combined use of kefir grain and beverage-a dual-source of live microbes and fermentation metabolites-as a potent probiotic intervention, capable of reducing pathogen proliferation, limiting organ and inflammatory damage, and modulate host immune responses during Salmonella infection in this rat model. Unlike prior studies focusing on the kefir beverage alone, our work demonstrates the synergistic protective effect of grain + beverage against Salmonella infection.

Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses continue to impose a global health burden due to their high transmissibility and limited antiviral options. MicroRNAs (miRNAs) have emerged as critical regulators of host pathogen interactions by modulating innate immunity, inflammatory signaling, and viral replication. This review focuses on respiratory RNA and DNA viruses that primarily infect the airways, including influenza viruses, RSV, human metapneumovirus, rhinoviruses, adenoviruses, and SARS-CoV-2. Several miRNAs, including miR-155 and miR-146a, are upregulated during infections with SARS-CoV-2, influenza, and RSV, where they fine-tune interferon and NF-κB signaling pathways. In contrast, downregulation of miR-21, miR-223, and let-7 family members has been linked to enhanced viral replication and dysregulated immune responses. Moreover, miR-122, miR-29a, and miR-124 have gained attention as potential therapeutic targets or prognostic biomarkers due to their roles in modulating viral load, cytokine production, and tissue injury. This review synthesizes current evidence on miRNA-mediated regulation of respiratory viruses, evaluates their promise as therapeutic candidates and diagnostic tools, and discusses delivery systems designed for targeted miRNA modulation. Despite promising advances, challenges remain in achieving tissue-specific delivery, avoiding immune off-target effects, and validating efficacy in clinical settings. Most of the available data are derived from in vitro or animal models and heterogeneous clinical cohorts, so conclusions about causality and therapeutic efficacy should be viewed as provisional and highlight significant translational gaps. Finally, we outline major challenges and future research directions needed to translate miRNA-targeted therapies into clinically viable antiviral strategies. Insights from these emerging studies position miRNA-targeted interventions as a potential new class of antiviral therapeutics and underscore the need for rigorous, translational research to realize their clinical utility.

Background: While systemic inflammation and metabolic dysregulation contribute to acute ischemic stroke (AIS)development, the function of the peripheral blood microbiome, which reflects systemic states, remains unclear. This study aimed to characterize these blood microbial signatures and define their clinical relevance in AIS.

Methods: Blood microbiome profiles from 61 AIS patients and 54 controls were analyzed by 16S rRNA sequencing. Patients were stratified by baseline NIHSS scores and followed for 3-month outcomes to assess prognostic microbial signatures.

Results: AIS patients exhibited a distinct blood microbiota profile compared to controls, characterized by reduced richness and significant structural changes. These alternations included a reduction of key commensal bacteria, such as Akkermansia, and an increase in opportunistic taxa like Meiothermus. Crucially, these microbial dysregulations were strongly correlated with host metabolic parameters, including blood glucose, homocysteine, and lipid levels. However, classification models based on the blood microbial signature failed to predict disease severity and 3-month neurological outcomes. In contrast, alterations in the blood microbiome demonstrated potential as an indicator of AIS severity (AUC = 0.733).

Conclusion: Our findings reveal that the blood microbiome in AIS is highly dysregulated, reflecting the host's systemic metabolic health. This strong association suggests circulating microbial signatures could play a role in stroke's pathophysiology, potentially influencing metabolic and inflammatory processes. As a result, analyzing these signatures could lead to the development of minimally invasive biomarkers for disease assessment and may also reveal novel therapeutic targets for managing systemic dysfunction in stroke patients.

Dengue virus (DENV) remains a major global health concern, characterized by complex virus-host interactions that are not yet fully understood. Advances in transcriptomic technologies have become crucial for uncovering the molecular mechanisms underlying DENV infection. This review summarizes recent transcriptomic studies, spanning microarrays, bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), virus-inclusive single-cell RNA-seq (ViscRNA-seq), and spatial transcriptomics. that have deepened our understanding of how DENV modulates host gene expression. These approaches have revealed critical immune responses, viral evasion strategies, and gene expression signatures linked to disease progression and severity. Moreover, transcriptomic analyses have facilitated the discovery of potential biomarkers for early diagnosis and novel targets for antiviral therapy. By integrating findings from diverse experimental models and technologies, this review underscores the pivotal role of transcriptomics in elucidating DENV pathogenesis. Collectively, these insights provide a robust foundation for developing improved diagnostics and therapeutic interventions against dengue.

Phytophthora capsici is a destructive, broad-host oomycete that causes major agricultural losses. Yet how this generalist pathogen tailors its infection program to different plant species, especially at its natural entry site remains poorly understood. We profiled P. capsici during early crown infection of four hosts representing distinct compatibility outcomes (cucumber, melon, chili pepper CM334, and tomato) using pathogen-centered RNA-seq and microscopy. Disease progression and necrosis diverged sharply: tomato collapsed by 27 hpi, followed by melon (54 hpi), cucumber (102 hpi), and chili pepper (120 hpi). Pathogen transcriptomes were strongly host-dependent, with 4470 differentially expressed genes but only a small conserved core shared across hosts (436 induced; 415 repressed). In rapidly collapsing tomato infections, the pathogen upregulated glycolysis and fatty-acid metabolism and repressed HR-associated elicitin INF2B. In cucurbit infections, expression patterns were consistent with prolonged biotrophy, including increased carbohydrate metabolism, transport processes, and nutrient acquisition. In partially resistant CM334, pathogen profiles indicated constrained early colonization, with metabolic stress, cell wall remodeling, and broad effector repression. Co-expression analysis identified modules linked to colonization, nutrient exploitation, and pathogenesis/defense-related functions. dsRNA-mediated silencing supported these patterns: silencing Pc18476 and Pc9358 reduced pathogen growth on cucumber leaves (∼78% and ∼65%), and in stem assays reduced growth and/or prevented necrosis in CM334 and tomato. Together, these findings show that P. capsici achieves broad host range by dynamically tuning effector deployment and metabolism to host-specific constraints, resulting in divergent infection outcomes during early crown invasion.

The Bombyx mori nucleopolyhedrovirus (BmNPV) poses a serious threat to the sericulture industry, and its infection process is highly dependent on the remodeling of the host actin skeleton. When the virus infects Bombyx mori cells, it induces significant reorganization of the actin skeleton, promoting the polymerization of G-actin to form F-actin. During this process, the actin monomer-binding protein thymosin (BmTHY) can regulate the dynamic balance of the cytoskeleton by inhibiting microfilament polymerization. Previous research by our group revealed that after BmNPV infects BmN silkworm cells, the phosphorylation level at S68 of Thymosin significantly increases (1.99 fold), suggesting that the virus may inhibit BmTHY function by altering its charge level, thereby hijacking the host microfilament network to promote its own proliferation. Subsequent experiments demonstrated that the BmTHY S68D mutation, mimicking persistent phosphorylation, reduced the binding of BmTHY to actin monomers and promoted the polymerization of G-actin into F-actin. Thus, it can be concluded that BmTHY S68D might enhance BmNPV proliferation by promoting F-actin formation.

Viral keratitis & conjunctivitis result in multiple ophthalmic symptoms and even progress to vision loss without timely intervention. Although multitudinous pathogens can cause ocular infections, the regulatory mechanisms underlying virus-host interactions remain incompletely defined. Our clinical and mechanistic investigations identify the co-infection of herpes simplex virus type 1 (HSV-1) and adenovirus as a predominant etiology of viral keratoconjunctivitis in Shenzhen, China (2024). The viral co-infection causes both severe symptoms and inflammations in clinical cases and in vitro. Mechanistically, mTORC2-regulated autophagy plays a pivotal role in viral replication, with mTOR-targeted intervention demonstrating superior antiviral and anti-inflammatory efficacy in corneal epithelial cells. This study elucidates a novel regulatory mechanism of mTORC2 in HSV-1 and adenovirus infection, thereby providing novel targets for the development of drugs against viral keratitis & conjunctivitis.

Vibrio spp. are important bacterial pathogens in aquaculture and can also cause human infections worldwide. Antimicrobial peptides (AMPs) are natural molecules with broad-spectrum antibacterial activity and are therefore considered promising alternatives to conventional antibiotics. In this study, a potential anti-bacterial peptide (GITIQCILPGFVVSKLSKLK, AMP LRSG08) was identified from Penaeus vannamei using ultra-performance liquid chromatography-mass spectrometry and online software. The minimum inhibitory concentrations of AMP LRSG08 against Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio vulnificus were 2 μg/mL, 2 μg/mL, and 125 μg/mL, respectively. Furthermore, over 80 % of these bacteria were killed within 2.5 h. The AMP LRSG08 could selectively accumulate on the V. parahaemolyticus cell surface and disrupt the integrity of their cellular membranes, leading to nucleic acid leakage from these cells by specifically targeting the cell membrane. Additionally, AMP LRSG08 exhibited concentration-dependent binding to genomic DNA. In vivo studies further revealed that AMP LRSG08 significantly increased the 72 h survival rate of zebrafish infected with V. parahaemolyticus to 80.0 %. Moreover, LRSG08 exhibited nonhemolytic activity and low cytotoxicity in vitro, indicating a favorable biosafety. The present study not only offers valuable insights for the screening of potential antimicrobial peptides but also establishes a theoretical framework for effective prevention and control strategies against vibriosis in aquatic products.

Burkholderia pseudomallei, the causative agent of melioidosis, is a recognised bioterrorism threat. This microorganism produces a key quorum molecule, 3-Hydroxy-C₁₀ homoserine lactone (3-OH-C₁₀ HSL), which has shown to modulate host immune responses. This study investigated the impact of 3-Hydroxy-C₁₀ HSL on A549 cell line, with a focus on organelle stress and inflammatory responses. Treatment with 3-Hydroxy-C₁₀ HSL (100 μM, 2 h) induces a significant elevation of cytosolic calcium and endoplasmic reticulum (ER) stress, evidenced by BiP upregulation and activation of the PERK-CHOP axis, indicating activation of the unfolded protein response (UPR). Mitochondrial function was compromised, as shown by reduced ATP production, loss of mitochondrial membrane potential (MMP), and elevated mitochondrial ROS generation. Furthermore, lysosomal dysfunction was observed through decreased acridine orange puncta, along with TFEB upregulation and LAMP1 downregulation. Gene expression analysis (10 μM, 6 h) revealed activation of the inflammasome pathway, with increased expression of NLRP3, NLRC4, IL-1β, and IL-18, and enhanced secretion of pro-inflammatory cytokines IL-6, TNF- α, and INF- γ. Overall, 3-Hydroxy-C₁₀ HSL disrupts host cellular homeostasis and induces inflammatory stress, providing novel insights into the molecular mechanisms underlying B. pseudomallei mediated pathogenesis.