Microbiology and Immunology最新文献

Antibiotic-resistant bacteria have become a significant global threat to public health due to the increasing difficulty in treatment. These bacteria acquire resistance by incorporating various antibiotic resistance genes (ARGs) through specialized gene transfer mechanisms, allowing them to evade antibiotic attacks. Conjugation, transformation, and transduction are well-established mechanisms that drive the acquisition and dissemination of ARGs in Gram-negative bacteria. In particular, the horizontal transfer of plasmids carrying multiple ARGs is highly problematic, as it can instantly convert susceptible bacteria into multidrug-resistant ones. Transduction, mediated by bacteriophages that package ARG-containing chromosomal DNA from host cells, also plays a crucial role in ARG spread without requiring direct cell-to-cell contact. Recently, a novel horizontal gene transfer (HGT) mechanism involving outer membrane vesicles (OMVs) has been identified as a key player in ARG dissemination. OMVs—nanoscale, spherical structures produced by bacteria during growth—have been found to carry small plasmids and chromosomal DNA fragments containing ARGs from their host bacteria. This newly discovered transfer process, termed “vesiduction,” enables intercellular DNA exchange and further contributes to the spread of antibiotic resistance. Additionally, mobile genetic elements such as transposons, insertion sequences, and site-specific recombination systems like integrons facilitate rearrangement of ARGs, including their translocation between chromosomes and plasmids. This review explores the molecular mechanisms underlying the HGT of ARGs, with a particular focus on clinically isolated antibiotic-resistant Gram-negative bacteria.

The analysis of bacterial infections using animal models has primarily relied on the average evaluation of many individuals at specific time points. Consequently, tracking temporal changes in an infection within the same individual is challenging. InVivo imaging techniques enable the longitudinal assessment of infection in the same individual while reducing the number of animals required. Understanding the dynamics of bacterial infections over time is crucial for elucidating disease mechanisms and developing effective treatment strategies. In this review, we summarize the In Vivo imaging techniques used to detect bacterial colonization in deep tissues in animal models of bacterial infection, along with efforts to enhance their sensitivity. In particular, we introduce a recently developed In Vivo imaging system that employs near-infrared luminescence to achieve high sensitivity and versatility. Furthermore, we discuss strategies for further improving its sensitivity.

Hepatocellular carcinoma (HCC) is the primary form of liver cancer that poses a significant global health concern due to its increasing incidence rates and diverse etiology. Chronic infection induced by hepatitis B virus (HBV) is a prominent etiological factor influencing the development of HCC. Although recent advances in multi-omics approaches have facilitated extensive exploration of HCC molecular characteristics, translating the characteristics of subtypes into clinical applications has been challenging due to parameters like limited sample size and complex classifiers for early detection. In the present study, we performed transcriptomics profiling of HBV-infected HCC patient tissue data to gather comprehensive insights into the intricate molecular mechanisms underlying HBV-associated HCC, specifically, viral protein interactions that influence the expression of oncogenes. The 1059 differentially expressed genes (DEGs) identified across two GEO data sets revealed upregulation of cell cycle and mitosis-related genes, alongside downregulation of genes involved in fatty acid degradation and cytochrome P450 activity. CDK1 and CDC20 which are part of the top cluster and hub gene from interactome analysis were identified as potential markers for HBV-positive HCC through gene expression pattern and overall survival analysis. Additionally, 19 DEGs showing significance in HCC development were identified as interacting partners with HBV proteins. Among them, the interaction of HBsAg with ALB and SHBG and their downregulation correlates to the lower testosterone levels identified in HBV and HCC patients. Together, the study enhances the understanding of the heterogeneity and molecular pathogenesis of HBV-positive HCC.

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers, and immunotherapy targeting programmed cell death 1 (PD-1) has become a treatment option for recurrent OSCC after surgery and radiation therapy. However, few studies have identified definitive biomarkers for predicting patient response to anti-PD1 therapy in OSCC. In the present study, biopsy specimens were obtained from 23 patients with recurrent OSCC who were subsequently treated with anti-PD1 therapy. Immunohistochemical examinations of CD3, CD8, FOXP3, CD103, CD163, programmed cell death ligand 1 (PD-L1), HLA-A/B/C, HLA-DR, and β2 microglobulin were performed, and their correlation with clinical response was statistically analyzed. We found that an increased density of CD8-positive lymphocytes and increased PD-L1 expression predicted a favorable response to anti-PD1 therapy in recurrent OSCC. In contrast, clinical factors such as age and sex, and immune-related factors such as HLA-Classes I and II, were not associated with the response to anti-PD1 therapy. Taken together, our results suggest that immunohistochemical analysis of CD8 and PD-L1 may be useful for predicting the efficacy of anti-PD1 therapy in recurrent OSCC.

Crohn's disease‒associated adherent-invasive Escherichia coli (AIEC) colonizes the gut lumen through Type 1 fimbriae. We demonstrated that the two-component signal transduction system BasRS is involved in the expression of fimbriae in the AIEC strain LF82, as evidenced by the reduced transcriptional activity of fimA in an LF82 mutant lacking BasRS. Consequently, the basRS mutant showed decreased invasiveness to HeLa cells, which was restored by introducing a plasmid expressing fimbriae in a BasRS-independent manner. These findings may provide new prospects for developing therapeutic interventions for AIEC-related Crohn's disease.

Lipoproteins are a class of potential vaccine candidates for Streptococcus pyogenes. The present study was conducted to purify and detect the immunogenicity of the fusion protein HtsA + FtsB of the iron transport lipoproteins HtsA and FtsB of S. pyogenes. The recombinant expression vector pBAD-htsA + ftsB was successfully constructed, and the fusion protein HtsA + FtsB with a purity above 95% was successfully obtained. Western blot analysis confirmed that the HtsA + FtsB fusion protein had good antigenicity and could be specifically recognized by both HtsA antiserum and FtsB antisera, and the antibody specificity of the HtsA + FtsB fusion protein was good. ELISA results showed that IgG antibody levels were significantly increased in the HtsA + FtsB fusion protein immunization group compared to the PBS control group. Additionally, cytokine levels, including IL-2, IFN-γ, IL-4, IL-6, and IL-17A, were significantly elevated. Furthermore, the antiserum from HtsA + FtsB-immunized mice enhanced the opsonophagocytic activity against S. pyogenes. The HtsA + FtsB fusion protein has strong immunogenicity and potential as a candidate vaccine for S. pyogenes.