Frontiers in Cellular and Infection Microbiology最新文献

Infectious Bursal Disease Virus (IBDV) (Avibirnavirus genus, Birnaviridae family) is a non-enveloped virus with a double-stranded RNA (dsRNA) genome. IBDV causes a highly contagious and immunosuppressive disease in domestic chickens (Gallus gallus), representing a major threat to the global poultry industry. Apoptotic cell death and exacerbated innate immune responses have been implicated in IBDV pathogenesis. Previous studies from our laboratory demonstrated the crucial role of type I interferon (IFN) in triggering apoptosis in IBDV-infected cell cultures. Genomic IBDV dsRNA is recognized by the cytoplasmic pattern recognition receptor (PRR) melanoma differentiation-associated gene 5 (MDA5) in chicken cells, triggering type I IFN responses. However, the contribution of the endosomal PRR Toll-like receptor 3 (TLR3) dsRNA sensor on type I IFN production upon IBDV infection has not been studied, despite several studies have demonstrated that its expression is significantly upregulated upon IBDV infection. Here, we demonstrate that ablation of TLR3 gene expression in DF-1 chicken fibroblasts results in a complete blockade of IBDV-induced apoptosis, a marked reduction in IFN production, and a significant enhancement of virus progeny yields. Notably, this effect appears to be specific to IBDV, as it was not observed with any of the other RNA viruses tested, including single-stranded RNA (ssRNA) viruses such as vesicular stomatitis virus (VSV), Semliki Forest virus (SFV), and Newcastle disease virus (NDV), nor even with the dsRNA virus avian reovirus (ARV). Our findings also suggest that TLR3 may also play a role in viral release into the extracellular space. Additionally, receptor interacting protein kinase 1 (RIPK1), a protein that interacts with TLR3 through the adaptor Toll/IL-1 receptor (TIR) domain-containing adaptor-inducing interferon-β (TRIF), was shown to contribute to both IFN production and apoptosis in response to IBDV infection or dsRNA stimulation in DF-1 cells. Overall, this study provides new insights into the innate immune recognition of IBDV, highlighting the central role of TLR3 in mediating antiviral responses in chicken cells.

Mitochondria are central hubs integrating cellular bioenergetics, redox balance, innate immune signaling, and metabolic homeostasis. During bacterial infections, these organelles are recurrent targets of pathogen-derived toxins, secreted effectors, and host inflammatory mediators, leading to a state broadly defined as mitochondrial stress. This stress encompasses alterations in oxidative phosphorylation, mitochondrial dynamics, calcium handling, reactive oxygen species (ROS) production, and activation or disruption of mitochondrial quality control pathways such as mitophagy. In this perspective, we propose mitochondrial stress as a conceptual framework linking bacterial infection and post-infectious metabolic disease. Using enteric bacterial pathogens such as Salmonella enterica serovars Typhimurium and Typhi, together with Vibrio parahaemolyticus, as conceptual models, we synthesize current evidence showing how distinct bacterial strategies converge on mitochondrial dysfunction and immunometabolic reprogramming of host cells. We argue that, while mitochondrial stress responses may initially support antimicrobial defense, their incomplete resolution may contribute to long-lasting metabolic and inflammatory alterations in epithelial, immune, and metabolic tissues. Persistent mitochondrial dysfunction may contribute to insulin resistance, chronic inflammation, and increased susceptibility to metabolic disease after infection. By framing mitochondrial stress as a central integrator of infection and metabolism, this perspective highlights key knowledge gaps and identifies mitochondria-centered pathways as potential targets to prevent or mitigate post-infectious metabolic sequelae.

Introduction: Periodontitis has been epidemiologically linked to an increased risk of Alzheimer's disease (AD), yet the mechanistic contribution of periodontal pathogens remains insufficiently understood. Building on our previous findings that Porphyromonas gingivalis outer membrane vesicles (OMVs) induce cardiovascular dysfunction, this study investigates whether these vesicles also drive AD-related pathology using the zebrafish model.

Methods: We microinjected P. gingivalis OMVs into the common cardinal vein of zebrafish larvae to evaluate locomotor behavior, brain injury, and neuroinflammatory responses. Integrated proteomic and transcriptomic analyses were performed to identify alterations in AD-associated pathways, and acetylcholinesterase activity along with Aβ1-42 plaque accumulation were quantified to validate hallmark AD phenotypes.

Results: OMV exposure resulted in significant neurotoxicity, locomotor deficits, and robust neuroinflammation, accompanied by pronounced dysregulation of AD-related molecular pathways. Notably, OMVs markedly increased acetylcholinesterase activity and promoted Aβ1-42 deposition in larval brains.

Discussion: These findings demonstrate that P. gingivalis OMVs act as potent inducers of neuronal damage and AD-like pathological features in vivo, providing mechanistic insight into how periodontal pathogens may contribute to neurodegenerative disease progression.

Introduction: Streptococcus agalactiae (Group B Streptococcus, GBS) is a major pathogen of neonatal infections worldwide, with significant geographical variation in its prevalent sequence types (STs). In Shanxi, China, ST10 has emerged as the dominant lineage in perinatal infections, yet the mechanisms underlying its regional dominance remain unclear. This study aimed to investigate the molecular epidemiological basis for the predominance of ST10 in this region.

Methods: We analyzed 55 clinical Streptococcus agalactiae isolates (21 invasive, 34 colonizing) collected from a hospital in Shanxi, China. Multilocus sequence typing (MLST) was performed to determine sequence types. Virulence genes and the CRISPR1 (clustered regularly interspaced short palindromic repeats, CRISPR) system were detected by polymerase chain reaction (PCR). Statistical analyses were conducted to assess associations between ST10, CRISPR1, and virulence gene carriage.

Results: ST10 accounted for 50.9% (28/55) of all isolates, predominating in both invasive (13/21, 61.9%) and colonizing (15/34, 44.1%) groups. Invasive ST10 strains universally carried the virulence genes cylE, hylB, scpB, and bca (100%) and exhibited complete erythromycin resistance mediated by ermB (100%). The CRISPR1 system was highly prevalent in ST10 isolates (26/28, 92.9%), and its presence was significantly associated with the virulence genes cylE (69.8% vs 25.0%; P=0.014) and hylB (62.8% vs 16.7%; P=0.012).

Discussion: The findings delineate a "high-virulence/controlled-resistance" phenotype in the locally dominant ST10, characterized by a conserved virulence gene, stable chromosomal ermB resistance, and a high prevalence of CRISPR1. This suggests CRISPR1 may contribute to the fitness of the ST10 lineage by stabilizing chromosomal virulence and resistance determinants while potentially restricting plasmid acquisition. This study establishes CRISPR1 as a potential key driver of ST10 adaptation and a possible predictive marker for monitoring high-risk clones, providing a rationale for regionally tailored prophylaxis strategies.

Invasive pulmonary aspergillosis (IPA) is a severe deep-seated fungal infection caused by fungi of the genus Aspergillus. In recent years, its global incidence has shown a marked upward trend, posing a serious threat especially to immunocompromised patients, such as hematopoietic stem cell transplant recipients, cancer patients undergoing chemotherapy, and individuals on long-term glucocorticoid therapy. The core clinical dilemmas lie in the difficulty of early diagnosis and the narrow therapeutic window. Currently used clinical diagnostic indicators, including the galactomannan (GM) assay, (1,3)-β-D-glucan(G) assay, and imaging examinations, suffer from insufficient sensitivity or specificity, while traditional microbiological detection methods have a relatively long turnaround time. S100 calcium-binding protein A12 (S100A12) and Pentraxin 3 (PTX3) are both key molecules in the innate immune response of the human body, playing central roles in the immune regulation of infectious diseases. Recent studies have demonstrated that both molecules are abnormally expressed in IPA patients and may participate in the processes of Aspergillus infection recognition, immune clearance, and inflammatory regulation through synergistic effects, thereby providing new directions for the early diagnosis, disease assessment, and targeted therapy of IPA. This review will systematically elaborate on the molecular characteristics of S100A12 and PTX3, explore their synergistic mechanism and combined diagnostic value in IPA, and analyze their prospects for clinical application.

Viral infections pose significant challenges to global health. Lipid metabolism plays a crucial role in various biological processes, including cell membrane structure, signaling, and energy homeostasis. Recent studies have highlighted the intricate relationship between lipid metabolism and viral infections, revealing how viruses exploit host lipid pathways to facilitate their replication and assembly. This review aims to elucidate the mechanisms by which viruses manipulate lipid metabolism and the subsequent impact on antiviral immunity. We systematically analyze the biological basis of lipid synthesis and degradation, emphasizing the role of lipids in immune cell function and the regulation of antiviral responses. Furthermore, we explore how altered lipid metabolism can influence immune responses in disease states, providing insights into the differential utilization of lipid pathways by various viruses. This review highlights suggest potential therapeutic strategies, including the development of antiviral drugs targeting lipid metabolism, modulation of lipid pathways to enhance immune responses, and combination therapies that integrate lipid metabolism modulation with conventional antiviral treatments. Future research directions are proposed, focusing on the interaction between lipid metabolism and emerging viral strains, the application of metabolomics in viral infection studies. This comprehensive review underscores the significance of lipid metabolism as a novel host-pathogen interface, paving the way for innovative therapeutic approaches in combating viral infections.

Enterovirus D68 (EV-D68), a unique enterovirus resembling human rhinoviruses, was long considered to cause only sporadic outbreaks of mild, self-limiting respiratory infections mainly in children. However, over the past decade, EV-D68 has exhibited a biennial outbreak pattern across multiple regions worldwide, coinciding with an increased incidence of severe respiratory illnesses and cases of acute flaccid myelitis (AFM) in children. The immune system plays a crucial role in providing rapid and effective defense. Nonetheless, our knowledge of the complex interactions between EV-D68 and the host immune responses is still very limited. Additionally, clinical detection of EV-D68 remains challenging, and there are no FDA-approved vaccines or antiviral treatments available. Therefore, ongoing research should focus on understanding the pathogenic mechanisms of EV-D68, as well as the development of reliable diagnostic methods and therapeutic options to control EV-D68 spread. This review intends to examine the initiatives undertaken for clinical surveillance of EV-D68 outbreaks, the immune responses elicited by EV-D68, and its strategies for immune evasion. Additionally, it explores recent advancements in antiviral drug development, thereby providing a comprehensive overview of current knowledge and identifying prospective directions for future research.

Background: Retained metallic foreign bodies can lead to implant-associated wound infections through bacterial colonization and biofilm formation. We report a case of a wound infection associated with a retained metallic fragment caused by Staphylococcus arlettae (S. arlettae) and evaluate the organism's early biofilm formation on common implant metals.

Case presentation: A 33-year-old man sustained a crush injury to his right hand and forearm, resulting in extensive soft-tissue damage and vascular injury. Emergency surgical management included meticulous debridement and vascular reconstruction. Postoperatively, purulent wound infection was effectively managed following microbiological identification of S. arlettae and antibiotic susceptibility-guided therapy. The treatment regimen involved serial debridement along with stepwise adjustments in antimicrobial dosing. Follow-up revealed that the patient's hand function had recovered well.

Methods and results: In vitro assays were conducted to compare early bacterial attachment and biofilm formation of the clinical S. arlettae isolate on stainless steel 304 (SS304), stainless steel 316 (SS316), and titanium alloy (TC4). The results revealed material-dependent differences in initial adherence as well as early biofilm development, establishing a link between implant surface properties and bacterial colonization propensity.

Conclusions: This case underscores the clinical significance of retained metallic fragments as potential foci for S. arlettae infection, emphasizing the necessity for prompt debridement, targeted antimicrobial therapy, and consideration of implant material properties. In vitro evidence demonstrating differential biofilm behavior on SS304, SS316, and TC4 has important implications for surgical decision-making, selection of implants, management of wounds, and prophylactic antibiotic strategies aimed at mitigating implant-associated infections.

Background: Streptococcus mutans (S. mutans) is a primary cariogenic pathogen responsible for acid production, exopolysaccharides (EPS) production and biofilm formation. Two-component systems (TCS) regulate EPS metabolism, especially the VicRK TCS. Overexpression of antisense vicR (ASvicR) can reduce EPS production and thereby weaken the cariogenicity of S. mutans. Although the antimicrobial monomer dimethylaminohexadecyl methacrylate (DMAHDM) exhibits potent antibacterial properties, mature S. mutans biofilms can protect themselves by extracellular matrix. Emerging evidence suggests that genetic intervention enhances drug efficacy, yet the underlying regulatory mechanisms remain largely unexplored.

Objective: To investigate the chemical-genetic cooperative antibiofilm strategy inhibition and mechanisms of ASvicR overexpression combined with DMAHDM on S. mutans biofilm formation, acid and EPS metabolism, and cariogenicity through the VicRK system.

Methods: The minimal inhibitory concentration and minimal bactericidal concentration of DMAHDM and chlorhexidine were determined. Biofilm properties were evaluated via biomass assessment, EPS quantification, lactate production measurement, and colony-forming unit counting. Biofilm structures were examined by scanning electron microscopy. Mechanisms were investigated using RT-qPCR, zymography, and western blot. Rat caries model was employed to assess caries formation under different treatment conditions.

Results: The ASvicR strain exhibited an approximate 2-fold increase in susceptibility to DMAHDM and chlorhexidine. The combination treatment reduced biofilm CFU by approximately 4 log units, significantly lowered lactate and EPS levels, and resulted in a loose, porous biofilm structure. The expression levels of cariogenic virulence factors as well as the VicRK TCS genes and proteins were significantly downregulated. In vivo, the combined treatment reduced the overall caries severity score to 12.7% of the control group (p<0.05) without observing any systemic adverse effects.

Conclusion: The strategy of combining ASvicR overexpression with DMAHDM effectively modulates EPS metabolism and cariogenicity in S. mutans by interfering with the VicRK TCS, providing a potential therapeutic approach for clinical caries management.

Objectives: Recent studies suggest that various tumour types can be colonized by different microorganisms, but data on unusual opportunistic fungus - Pneumocystis jirovecii - remain scarce. Lung cancer patients are considered one of the risk groups for its infection. Since P. jirovecii tends to distribute focally within the lungs, this study aimed to determine whether it can be detected in lung tumour tissue.

Methods: Fragments of neoplastic tissue (NPL), normal adjacent tissue (NAT) and respiratory secretions (RS) were collected from 70 patients with histologically confirmed primary lung cancer. DNA was extracted and analysed by nested-PCR targeting the mtLSU rRNA and CYB loci, followed by genotyping.

Results: Pneumocystis jirovecii was detected in fourteen samples derived from 8/70 individuals (11.4%): two NPL, six NAT and six RS. In two patients, Pneumocystis was detected in all three specimen types; both were diagnosed with the same histological malignancy grade (G3, P=0.036). The genotype distribution varied across sample types in most cases.

Conclusions: The ability of Pneumocystis to colonize NPL may be linked to the stage of tumour advancement, suggesting that local tumour-related factors could influence its colonization. These findings support further investigation of the lung microbiome in the context of tumour-associated microenvironments and their potential utility as complementary biomarkers in lung cancer.