生物学最新文献

The oral cavity contains the second most diverse bacterial community after the intestines, with bacteria and viruses coexist. Streptococcus mutans is a major pathogenic bacterium in the oral cavity, commonly associated with dental caries. We investigated the effects of S. mutans-derived extracellular vesicles (Sm EVs) on herpes simplex virus 1 (HSV-1) infection, which is prevalent in the oral cavity. We performed our experiments in human oral keratinocyte (HOK) cells and mucosal tissue-derived organoids, and analyzed human whole saliva (n = 50) for associations between S. mutans and HSV-1 envelope glycoprotein D (gD) mRNA levels by qPCR. Sm EVs significantly enhanced HSV-1 production in mucosal organoids. Indeed, mRNA and/or protein levels of type I (IFN-α and IFN-β), type II (IFN-γ), and type III (IFN-λ₁, IFN-λ₂, and IFN-λ₃) interferons were significantly lower in Sm EV-treated mucosal organoids compared with the vehicle control under mock-infection. When HSV-1 was introduced after Sm EV pretreatment, these IFN levels showed a general trend of statistically significant reduction compared with those in the vehicle control. Moreover, Sm EVs suppressed IFN mRNA and protein levels by upregulating the EGFR - ERK pathway in mucosal cells, creating an environment that enhances HSV-1 production. Interestingly, a positive correlation was noted between S. mutans and HSV-1 detected in human whole saliva samples. These results suggest that S. mutans can negatively modulate the host innate antiviral responses by secreting EVs, thereby enhancing viral production. This study might provide a new perspective for controlling viral infections in humans.

Sindbis virus (SINV), a widely distributed alphavirus, is both a foundational model for viral replication studies and an underrecognized human pathogen. Despite its typically mild presentation, SINV can lead to prolonged joint pain and, in rare cases, neurological complications. This review explores SINV's molecular biology and clinical manifestations, particularly its role in causing Sindbis Fever - a self-limiting but potentially chronic arthritic disease. Molecular insights reveal mechanisms of immune evasion, neurovirulence, and persistent infection, highlighting SINV's potential for broader public health impact, especially under changing climatic conditions. This review also identifies key virulence determinants and discusses the virus's utility as a model for studying alphaviral encephalitis. Continued research is essential to better understand SINV pathogenesis and to prepare for potential outbreaks.

Bacterial metabolism is important for antibiotic resistance and tolerance. However, the impact of indole on bacterial metabolism and antibiotic efficacy has not been fully elucidated. In this study, we investigated the effect and specific mechanism of exogenous indole on the antibiotic susceptibility of Edwardsiella tarda, a common pathogen in freshwater and marine fish farming. We found that exogenous indole promoted E. tarda tolerance to the antibiotic florfenicol, and reprogrammed the E. tarda metabolome. A total of 108 metabolites were detected, including 66 differential metabolites that regulate various metabolic pathways, such as the tricarboxylic acid (TCA) cycle and nucleotide metabolism. Exogenous indole disrupted the TCA cycle in E. tarda by increasing the intracellular NADH contents and activating the respiratory chain to increase the reactive oxygen species levels, thereby increasing the intracellular Fe²⁺ content to activate the Fenton reaction, which in turn promotes the oxidative stress response. Furthermore, indole inhibited antibiotic entry into the cell and activated efflux pumps to reduce the intracellular antibiotic content, ultimately promoting antibiotic tolerance. In vivo, exogenous indole compromised the ability of florfenicol to protect fish survival and eliminate pathogenic bacteria. These results shed light on the metabolic changes induced by indole and suggest future directions for addressing antibiotic tolerance and clinical infections of E. tarda in aquaculture. This study serves as a reminder of the adverse effects of combining antibiotics with metabolites in aquaculture.

Angelman syndrome (AS) is a rare neurogenetic disorder characterized by developmental delay, speech impairment, ataxia, epilepsy, and in some cases hyperphagic feeding behavior. AS is caused by loss of function mutations, loss of expression, or maternal allele deletion of the E3 ubiquitin ligase UBE3A. Recent work has identified a connection between UBE3A and the mechanosensitive ion channel PIEZO2, raising the possibility that UBE3A may regulate PIEZO-dependent satiety signaling. In this study, we investigated the role of the Drosophila UBE3A ortholog, Dube3a, in Piezo-associated feeding behaviors. Single-cell RNA-sequencing data revealed overlapping expression of Dube3a and Piezo within crop and enterocyte populations of the gut, identifying a relevant cellular context for this pathway to occur. We developed a novel feeding assay using GFP-expressing yeast to quantify food intake and gut distention in vivo. Dube3a loss-of-function (Dube3a^15b) flies exhibited hyperphagia and gut distention nearly identical to Piezo knockout flies. Analysis of chromosomal deficiency lines spanning the Dube3a locus further supported a requirement for Dube3a in normal satiety signaling. Finally, biochemical analyses demonstrated that Dube3a knockdown results in decreased Piezo protein levels, consistent with an indirect regulatory relationship. Together, these findings identify Dube3a as a critical regulator of Piezo-dependent satiety pathways and suggest that dysregulation of mechanosensory signaling may contribute to hyperphagia observed in AS. Further work is needed to define the intermediate factors linking UBE3A activity to Piezo stability and function.

This study investigated the role of COPB2 in gastric cancer (GC) pathogenesis. Analysis of TCGA datasets and tissue microarrays revealed its upregulation in GC tissues compared to normal adjacent tissues, which was correlated with advanced tumor stage and lymphatic invasion and demonstrated significant diagnostic value (AUC = 0.895 and 0.851). Functional assays using lentiviral-mediated silencing in GC cells showed that COPB2 knockdown suppressed cell proliferation and migration, induced G0/G1-phase arrest, and promoted apoptosis. Mechanistic investigations through microarray, KEGG, and IPA analyses indicated that COPB2 dysregulation inactivated the PI3K/AKT and NF-κB signaling pathways. This led to the downregulation of key oncogenic effectors including Slug, FN1, CDH2, F2RL1, CDK6, CCND1, MMP9, CDKN2A, and SQSTM1, while upregulating tumor suppressors CDKN1B, CDKN1A, and DDIT3. In conclusion, COPB2 acts as an oncogene in GC, driving tumor progression through modulation of the cell cycle and key signaling pathways, highlighting its potential as a therapeutic target.

EPB41L1-5 is known to maintain cell morphology and signal transduction, with evidence suggesting it can inhibit tumor progression. However, its role in kidney renal clear cell carcinoma (KIRC) is not fully understood. This study evaluated EPB41L1-5's prognostic value in KIRC using bioinformatics methods and validation through qPCR, immunohistochemistry, and cell functional experiments. The results demonstrated a decreased expression of EPB41L in KIRC tissue compared to normal renal tissue, correlating with lower survival rates. Low EPB41L expression was also associated with overall survival in KIRC. Additionally, EPB41L was found to be involved in extracellular matrix regulation, G protein-coupled receptor ligand binding, and multiple immune cell infiltrations. In addition, their elevated methylation levels are associated with poor prognosis in KIRC patients. Overall, EPB41L family is a potential molecular marker for predicting KIRC prognosis, offering insights for therapeutic development.

Small extracellular vesicles (sEVs) play a role in the pathophysiology of viral respiratory infections and may be suitable biomarkers for COVID-19 and Influenza infections, or targets for treatment. We investigated differences in the surface proteome of plasma sEVs in patients with COVID-19 and Influenza. In a discovery cohort with 117 patients, we used a random forest (RF) classifier in order to discriminate COVID-19 and Influenza patients based on routine clinical parameters. Furthermore, plasma samples from these patients were analyzed with an EV Array containing 33 antibodies to capture sEVs, which were then visualized with a combination of CD9, CD63, and CD81 antibodies. We applied an RF classifier and a random depth-first search (RDFS) approach to extract markers with the best discriminatory potential. Data were then validated in an independent set of patient samples on a chip-based ExoView platform.In the initial cohort of 117 patients, leukocyte numbers, and heart rate discriminated best between COVID-19 and Influenza infection. In the plasma samples, 32 EV surface markers could be detected. Feature panels containing CD9, CD81, and CD141 allowed a discrimination between COVID-19 and Influenza. Consecutively, increased CD9 abundance was validated in a second, independent cohort, with the ExoView technology. The increased CD9 signal in Influenza patients was confirmed and shown to be mostly driven by CD9/CD41a double positive sEVs, hinting at a thrombocyte origin.We identified leukocyte numbers and heart rate, as well as CD9 as a sEV surface marker to differentiate COVID-19 from Influenza patients.

Mycoviruses are increasingly recognized for their potential applications in crop protection, particularly in biocontrol of phytopathogenic fungi and in enhancement of the environmental competence and virulence of entomopathogenic ascomycetes (EA) to optimize their pest control potential. Here, we provide the first evidence of a functional switch between insect-pathogenic and nonpathogenic states in a strain of the EA Beauveria bassiana, driven by a Beauveria bassiana victorivirus 1 (BbVV-1) acting as an essential virulence determinant. The mycovirus-infected wild-type strain (WMI) demonstrated broad-spectrum virulence across insect orders, whereas the isogenic mycovirus-free strain (MFr) was entirely nonpathogenic, exhibiting a complete suppression of cuticle penetration capability, which was restored only through injection of conidia into the hemocoel, bypassing the cuticle barrier. A comprehensive analysis of mycovirus-related inhibition of cuticle penetration revealed that WMI exhibited strong activity in extracellular cuticle-degrading enzymes (ECEs) relevant to virulence, with emphasis on Pr1 protease, whereas ECE secretion, and notably Pr1, were markedly suppressed in MFr. Insect infection by WMI showed a time-dependent increase in the number of pr1 gene copies and quantity of fungal DNA, while neither pr1 expression nor fungal DNA were detected in MFr during the infection cycle. Downregulation of the pr1 gene in MFr suggests a direct effect of mycovirus on fungal transcriptional regulation, highlighting the potential to deploy this BbVV-1 to produce hypervirulent EA strains but also to transition EA from entomopathogens to solely plant-beneficial microorganisms.

Influenza H3N8 viruses have been frequently isolated from chicken farms. However, comprehensive characterization of their virological properties, molecular evolution, virulence, and risk of spillover into mammals remains limited. In particular, little attention has been given to the transmission efficiency of H3N8 avian influenza viruses among chickens and their spillover risk. Here, we systematically characterized H3N8 isolates obtained from asymptomatic chickens through multidisciplinary approaches, including genomic surveillance, receptor binding profiling, and in vivo pathogenicity and transmission assays. All strains showed >98% nucleotide homology with human-infecting strains. Phylogenetic analysis revealed that their internal genes were derived from H9N2, while HA and PB2 genes shared high homology (bootstrap support >98%) with the novel H3N3 virus. All isolates maintained avian-type receptor-binding motifs (HA-Q226/G228) while exhibiting dual α2,3/α2,6-sialic acid binding and robust replication in mammalian cells (peak MDCK titer: 10⁷·⁵ TCID₅₀/mL). ZJ07 demonstrated exceptional thermostability (HA activity persisting >3 hr at 56°C), while JS13 showed 1.8-fold elevated neuraminidase activity versus controls (p < 0.05). In vivo, all strains caused subclinical infections with broad tissue tropism in chickens and mice without adaptation, transmitting efficiently among direct-contact poultry. Strikingly, AH12 achieved 100% airborne transmission in chickens. These findings confirm H3N8's capacity for silent poultry circulation and identify key features conducive to cross-species infection, including dual receptor binding, infection in a mammalian model, and high genetic homology with human strains. The airborne transmissibility of AH12 underscores a heightened spillover risk, necessitating enhanced surveillance and vaccines targeting avian-human interface strains.