Cellular Microbiology最新文献

Extracellular vesicles (EVs) are nanovesicles secreted by cells with lipid bilayer structure, which play a key role in the communication between bacteria and host cells. This paper reviews the role of EVs, particularly bacterial-derived EVs (bEVs) and host cell (e.g., macrophage)-derived exosomes, in the regulation of macrophage polarization during bacterial infection. Macrophages can differentiate into M1 and M2 types with different functions, which is very important in the innate immune response. bEVs and exosomes influence the polarization state of macrophages by carrying a variety of bioactive molecules, such as bacterial effectors, nucleic acids, and lipids, and finally, they are involved in the regulation of host immune and inflammatory responses. In addition, EVs show great potential in early disease diagnosis, vaccine development, and targeted therapy. However, the application of EVs still faces many challenges, including the development of isolation and purification techniques, the establishment of standardized processes, and the clarity of specific mechanisms. In this review, the mechanism of bEVs and exosomes in regulating macrophage polarization is systematically summarized, their potential applications in infectious diseases are explored, and directions for future research are proposed. With a deeper understanding of the function and regulatory mechanisms, EVs are expected to become a new diagnostic marker and a therapeutic tool, providing new strategies for the prevention and treatment of infectious diseases.

Research on Fusarium oxysporum f. sp. lini (Foln), a fungal pathogen of Linum usitatissimum L. (flax) responsible for significant crop losses, requires effective methods for visualizing fungus–plant interactions to improve understanding of this pathosystem. In this study, transgenic Foln strains expressing GFP or dsRed fluorescent markers were generated via Agrobacterium-mediated transformation. Several Agrobacterium tumefaciens strains were tested, and those with the highest transformation efficiency were selected. Transformants were screened based on phenotypic characteristics and further validated using molecular biology techniques. Since transgenesis can influence a fungus′s ability to infect its host, the pathogenicity of the generated Foln lines was assessed by measuring the expression levels of pathogenesis-related genes and ROS metabolism-related genes, alongside quantifying O₂⁻ and H₂O₂ levels in the infected plant tissue. The presence of dsRed and GFP fluorescent markers was confirmed using fluorescence microscopy. Ultimately, two transformants exhibiting pathogenic characteristics similar to the wild-type Foln strain were selected. These transformants represent valuable tools for further studies of Foln pathogenesis in flax. Additionally, the workflow developed here can be adapted to generate fluorescent transformants of other F. oxysporum pathogenic strains.

X. Yang, C. Zhao, G. Bamunuarachchi, et al., “miR-193b Represses Influenza A Virus Infection by Inhibiting Wnt/β-Catenin Signalling,” Cellular Microbiology 21, no. 5 (2019): e13001, https://doi.org/10.1111/cmi.13001.

In the article titled “miR-193b Represses Influenza A Virus Infection by Inhibiting Wnt/β-Catenin Signalling,” there was an error in Figure 2a, where the images duplicated in miR-Con and miR-1-1 as well as miR-193b and miR-509-1 blots. The corrected figure is shown below and is listed as Figure 1:

We apologize for this error.

Glioblastoma, the most aggressive and fatal form of brain tumor, is characterized by rapid growth, extensive invasion of surrounding tissues, and significant angiogenesis. These and other types of cancer remain a leading cause of mortality worldwide, with conventional treatments such as chemotherapy, radiation, and surgery often limited by significant side effects. This has led to the pursuit of novel therapeutic approaches, including bacterial therapy, which utilizes bacteria’s unique ability to target tumor microenvironments and deliver therapeutic agents. This research examines the antitumor effects of Streptomyces sp. M12 extract on the U87_MG glioblastoma cell line. The cytotoxicity of the extract was assessed using the MTT assay. Additionally, flow cytometry and scratch assays were conducted to evaluate cell migration. Furthermore, gene expression analysis for Bax, Bcl-2, Caspase-8, and Caspase-9 was performed to determine apoptotic effects. The MTT assay indicated strong anticancer activity with an IC₅₀ value of 17.72 after 96 h of treatment. In vitro studies showed that the extract significantly promotes apoptosis, as evidenced by an 83.6% increase in apoptosis rates via flow cytometry. Moreover, the scratch assay demonstrated that the extract inhibited U87_MG cell migration, indicating antimetastatic potential. Real-time PCR analysis results revealed a 1.972-fold increase in Caspase-8 expression and a 0.468-fold decrease in Caspase-9 expression (p ≤ 0.001), suggesting that apoptosis is triggered through the extrinsic pathway. These findings emphasize the dual cytotoxic and antimigratory effects of the strain M12 extract, making it a promising candidate for glioblastoma treatment. Further investigation is necessary to clarify the molecular mechanisms involved and confirm its therapeutic potential in preclinical and clinical settings. This study highlights the significance of natural products, particularly those derived from Streptomyces sp. M12, an innovative cancer treatment strategy.

Klebsiella pneumoniae is a ubiquitous Gram-negative bacterium and a common cause of pneumonia, which leads to intense lung injury and mortality that are correlated with deregulated inflammation. Emerging evidence indicates that the NLRP3 inflammasome plays a critical part in regulating inflammatory processes in various infectious diseases. However, its role in K. pneumoniae infections remains elusive. In this study, we identified a siderophore, enterobactin (Ent), from K. pneumoniae as a key factor that induces NLRP3 activation in both the pulmonary epithelial cell line A549 and lung tissue from K. pneumoniae–infected mice. A549 epithelial cells infected with an Ent-deficient mutant (ΔentB) had lower Nlrp3, Asc, and Pro-caspase-1 gene expression, caspase-1 activity, and IL-18 secretion than cells infected with wild-type K. pneumoniae. No such effect was observed with THP-1 macrophages. Ent induced NLRP3 activation and IL-18 production in lung tissue of mice intranasally infected by K. pneumoniae strains. Interestingly, the recruitment of immune cells and production of inflammatory cytokines and chemokines were comparable in wild-type and ΔentB strain–infected mice. Taken together, our findings provide the first example of Ent playing a role in host inflammation control by targeting NLRP3.

Inflammatory bowel diseases are a group of chronic diseases with increasing global incidence and rising morbidity and mortality, contributing to a significant health burden. Mainstream treatments for IBD are focused on controlling inflammation and alleviating the symptoms, also aiming for intestinal barrier repair. Understanding the cellular and molecular mechanisms underlying intestinal inflammatory disorders is the key to developing more targeted therapies to treat IBD. The growth, differentiation, and proliferation of intestinal epithelial cells require energy. Since mitochondria provide the energy also required for intestinal epithelial cells to maintain homeostasis and barrier integrity, their dysfunction can lead to cell death and inflammation. While several studies have confirmed the link between gut microbial metabolites and mitochondrial function, conflicting results from studies in IBD models have presented challenges to a detailed understanding of this area. This review focuses on presenting data from existing literature and highlighting the therapeutic potential of gut microbiota–derived metabolites in restoring mitochondrial function, which may likely develop into therapeutic interventions in IBD.

Trial Registration: ClinicalTrials.gov identifier: NCT01473524, NCT03724175

The epidermal growth factor receptor (EGFR), a protein located on the cell surface, belongs to the tyrosine kinase family and plays a crucial role in cell development and proliferation. Abnormal expression or mutations in the EGFR gene can lead to non–small cell lung cancer. Although established EGFR inhibitors have been effective in the treatment of cancer, they are associated with several side effects. As a result, there is an urgent need to develop novel EGFR inhibitors that can effectively target the receptor while causing no adverse side effects. In this study, a series of bis(6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione derivatives was synthesized in water at room temperature without the use of any catalyst, and pharmaceutical properties are investigated. Computational methods, including density functional theory (DFT), molecular docking, and molecular dynamics (MD), were utilized to investigate the chemical properties, drug-like characteristics, and anticancer potential of the molecule. Quantum chemical calculations indicated that the molecules are relatively stable and exhibit significant electrophilic properties. The analysis of HOMO-LUMO contour maps was conducted to illustrate charge density distributions that may be associated with biological activity. Docking studies with EGFR enzymes indicated that all compounds demonstrated favorable binding affinities, with docking scores ranging from −4.412 to −6.158 kcal/mol. Particularly, Compound 3f, with an energy of −6.158 kcal/mol, showed the best binding affinity, outperforming the native ligand, which had a docking score of −5.076 kcal/mol. The stability of the EGFR-3f complex is significantly enhanced by the formation of five conventional hydrogen bonds and one carbon–hydrogen bond in ligand–protein interactions. MD simulations, which included analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (rGyr), molecular surface area (MolSA), and polar surface area (PSA), were conducted on the EGFR-3f complex. It was found that the EGFR-3f complex is stable, and the results show that Compound 3f has a strong interaction with the target enzyme.

To explore the peculiarities of neutrophil motility, two models of chemoattraction were created: a horizontal model, where a container with bacterial chemoattractant was attached laterally to the endotheliocyte monolayer, and a vertical model, simulating a pyemic focus in the lower part of the modified Boyden chamber. Low-molecular weight product secretion and/or degradation of Enterococcus faecalis caused “disorientations” of neutrophil migration with hyperproduction reactive oxygen species (ROS) by immune cells, while Proteus mirabilis inhibited both migration of most neutrophils and the production of ROS by them, while the activity of the remaining uninhibited neutrophils increased. Neutrophils generated ROS during migration, especially actively in the case of a large number of mobile cells (under stimulation with low-molecular weight product secretion and/or degradation of Enterococcus faecalis and Escherichia coli). Using high-resolution microscopy, it was shown that low-activity neutrophils cause changes in the morphology of endothelial cells during migration more than high-activity neutrophils. In the vertical migration model, the morphology of endothelial cells significantly changed during neutrophils diapedesis. It was observed that space between endothelial cells was increased (especially in the case of neutrophil swarming).