Microbial pathogenesis最新文献

To investigate the effects of host species and altitude differences on the rumen fungal community (RFC), this study selected Zhongdian yellow cattle and Zhongdian yaks from high-altitude regions (Shangri-La, 3600 m) and Jiangcheng yellow cattle and Jiangcheng water buffalo from low-altitude regions (Jiangcheng, 1100 m) in Yunnan Province as research subjects. The ITS2 high-throughput sequencing (HTS) technology was applied to analyze the composition and diversity of their rumen fungi. The results showed no significant differences in the RFC between different host species within the same altitude environment (P > 0.05), whereas significant differences were observed in the fungal community structure between different altitude groups (P < 0.01). This indicates that under consistent dietary conditions, altitude is the primary factor driving differences in the RFC, while the influence of host species is relatively limited. Our study provides a theoretical basis at the fungal level for understanding the mechanisms of interaction between plateau ruminants and microorganisms.

Objective: This study aimed to investigate the antimicrobial and anti-inflammatory effects of Yinhuapinggan Granules (YHPG) in combination with cefotaxime (CTX) against extended-spectrum beta-lactamase-producing Escherichia fergusonii (ESBL-EF), focusing on how YHPG enhances antibiotic efficacy and modulates inflammatory pathways associated with acute lung injury (ALI).

Methods: The antimicrobial activity of YHPG and CTX was assessed by measuring the minimum inhibitory concentration (MIC) of CTX in the presence of YHPG. qRT-PCR was used to detect the expression of bacterial resistance genes, including acrA, acrB, tolC, OXA-2, TEM-1, and outer membrane porins ompC and ompF. Outer membrane permeability was evaluated using AKP and Bradford assays, while biofilm disruption was analyzed by laser confocal microscopy. In vivo, the effects of YHPG were evaluated in a mouse pneumonia model induced by ESBL-EF infection, including lung index, histopathological changes, and inflammatory cytokine levels. Inflammatory cytokine levels were measured in serum, and the expression of key genes in the NLRP3 inflammasome pathway was analyzed by qRT-PCR.

Results: The combination of YHPG and CTX significantly inhibited the growth of ESBL-EF and enhanced its outer membrane permeability. Additionally, YHPG modulated the expression of key bacterial resistance genes, including acrA, acrB, tolC, OXA-2, and TEM-1, as well as the outer membrane porins ompC and ompF. YHPG also effectively disrupted the biofilm structure of ESBL-EF, reducing its protective barrier. In vivo, YHPG treatment alleviated pulmonary inflammation and tissue damage in mice. Serum levels of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, were significantly reduced, indicating a potent anti-inflammatory effect. Furthermore, YHPG inhibited the activation of the NLRP3-ASC-CASP1-GSDMD signaling pathway, further mitigating inflammation and tissue damage associated with ESBL-EF infection.

Conclusion: YHPG enhances the antibacterial activity of CTX against ESBL-EF by increasing membrane permeability, disrupting biofilms, and modulating the inflammatory response. This study suggests that YHPG could serve as an adjunctive treatment for antibiotic-resistant infections, offering a promising approach to combat bacterial resistance and inflammation associated with ESBL-EF infections.

Bacterial wilt caused by Ralstonia pseudosolanacearum remains one of the most destructive diseases threatening eggplant production worldwide, as effective management options are limited, resistance in cultivated varieties is often unstable, and chemical control measures are largely ineffective and environmentally unsustainable. In this study, we profiled the rhizobacterial microbiomes of wilt-susceptible Solanum melongena and wilt-resistant S. torvum cultivated in contrasting soils from Cameroon and India representing non-endemic and endemic regions of bacterial wilt. A combined culture-dependent methodology together with 16S rRNA amplicon sequencing was used to elucidate the structure and functional attributes of the microbial communities. Soil origin was the principal factor influencing microbiome composition (PERMANOVA R² = 0.34, p = 0.001), followed by host genotype (R² = 0.21) and root niche (R² = 0.14). The wilt-resistant S. torvum consistently supported higher bacterial diversity and was enriched with core taxa, including Bacillus and Methanocella. Fourteen rhizobacterial isolates, mainly Bacillus spp., showed strong antagonistic activity against R. pseudosolanacearum. Metabolomic analyses using LC-QTOF-MS/MS and GC-MS indicated the production of lipopeptides and polyketides by Bacillus spp., while Pseudomonas plecoglossicida produced phenazine derivatives and indole-3-acetic acid. In greenhouse experiments, Bacillus cereus, B. velezensis, and Priestia megaterium significantly improved seed germination and seedling vigor at inoculum densities of 10⁶-10⁷ CFU mL^-1. Together, these results show that eggplant-associated rhizobacteria, particularly Bacillus spp. and P. plecoglossicida, contribute to bacterial wilt suppression and offer potential for sustainable disease management.

Staphylococcus aureus is a major human pathogen mainly involved in chronic biofilm-related infections, especially at epithelial surfaces and wound sites, owing to its ability to form antibiotic-resistant biofilms and release virulence factors. Conventional antibiotics often fail to eradicate established biofilms and may contribute to the emergence of drug resistance, underscoring the urgent need for alternative biofilm-inhibiting and antivirulence strategies. Herein, we synthesized several dicyclic peptides, including cyclo(L-Phe, L-Hyp) and its stereoisomers cyclo(L-Phe, D-Hyp) and cyclo(D-Phe, L-Hyp), to evaluate their ability to inhibit S. aureus biofilm formation. All cyclic dipeptides exhibited a minimum inhibitory concentration (MIC) of 1 mg/mL. Biofilm inhibition was assessed via crystal violet staining and confocal laser scanning microscopy. At 0.5 mg/mL (1/2 MIC), the compounds exhibited superior inhibition of 24 h biofilm formation compared with vancomycin, with cyclo(L-Phe, D-Hyp) showing the most profound inhibitory activity. qRT-PCR revealed that at 0.25 mg/mL (1/4 MIC), cyclo(L-Phe, D-Hyp) significantly downregulated the expression of the Agr-quorum-sensing system (RNAIII: -75.7%; hla: -61.7%; psm-α: -73.3%), the ica operon (icaA: -71%; icaD: -76.7%), and sarA (-69.3%) (P < 0.0001). Notably, cyclo(L-Phe, D-Hyp) showed low cytotoxicity (CC₅₀ = 5.13 ± 0.27 mg/mL) and negligible hemolysis (<1 %) at twice its MIC, indicating a favorable safety margin for antimicrobial use. These cyclo dipeptides can be formulated for topical delivery to sites such as skin, mucosa, or open wounds, providing a practical approach for localized treatment of biofilm-associated infections. These findings identify cyclo(L-Phe, D-Hyp) as a promising lead for the development of topical anti-infective agents targeting chronic S. aureus biofilm-associated infections.

Biofilms are microbial communities encased in an extracellular matrix, forming highly resistant structures. Klebsiella pneumoniae, a major opportunistic pathogen, exhibits strong biofilm-forming ability, posing serious challenges in healthcare and industry. Key issues include extreme antimicrobial resistance, immune evasion, and complex organization. Currently, no approved treatments specifically target K. pneumoniae biofilms, necessitating alternative strategies. A combined approach is essential for effective control. This review explores potential alternative therapies to complement conventional treatments, enhancing antibiotic efficacy and mitigating the harmful effects of these resilient bacterial communities.

Bivalve consumption presents a public health risk due to contamination with Vibrio parahaemolyticus, a leading cause of seafood-borne gastroenteritis. This study assessed the occurrence, pathogenicity, antimicrobial resistance, and biofilm-forming ability of V. parahaemolyticus in mussels and clams collected from the Aegean, Marmara, and Black Seas in Türkiye between May 2021 and May 2022. A total of 255 samples (135 mussels, 120 clams) were analyzed. The bacterium was detected in 32.2% of samples, with the highest occurrence (52.5%) observed in the low-salinity Black Sea. Pathogenic strains, carrying the trh gene, constituted 5.9% of all strains and were more frequently found in clams and during winter. All strains exhibited multidrug-resistance (MDR), showing resistance to at least four antimicrobial classes; notably, all were resistant to piperacillin and tetracycline. Biofilm formation assays revealed significant effects of temperature and incubation time: maximum biomass was observed at 25 °C after 48 h, while lower or higher temperatures, as well as shorter incubation, inhibited formation. Moderate biofilm production was observed only in clam-derived strains (7.1%). These findings demonstrate the influence of environmental and host-related factors on V. parahaemolyticus ecology and stress the need for species-specific monitoring strategies to safeguard seafood safety.

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.