Project description:Anaerobic bacteria in the oral cavity can cause respiratory infections. However, their precise mechanisms of action remain elusive. Unexpectedly, bacterial flora analysis using 16s rRNA revealed ‘hidden’ mixed infections of anaerobic bacteria and commensal oral Streptococcus species in community-acquired pneumonia. The purpose of this study is to elucidate the mechanisms by which Prevotella intermedia exacerbates oral streptococcal pneumonia.
Project description:Oral lichen planus (OLP) is a common oral mucosal disease, of which the etiology and pathogenesis are still unclear. Microorganisms may play an essential role in the pathogenesis of OLP. Previous studies of our group found that the composition ratio of Prevotella melaninogenica (Pm) on the buccal mucosa surface of OLP patients increased significantly. In addition, Pm could invade the epithelium of OLP. As the first physical defense of the oral mucosa, oral keratinocytes may interact directly with Pm in OLP. Therefore, this study aimed to explore the impact of Pm on primary human oral keratinocytes' transcriptome.
Project description:Background: The oral anaerobe Prevotella melaninogenica is enriched in the lungs of people with cystic fibrosis (pwCF), yet its functional impact on respiratory tract homeostasis remains incompletely understood. Prior studies identified immune modulatory effects following lung exposure to Prevotella, but the relevance of these findings for CF infections is unknown. Methods: The impact of P. melaninogenica on infection with the CF pathogen Staphylococcus aureus was evaluated using a mouse lung infection model and human respiratory tract cystic fibrosis transmembrane conductance regulator (CFTR) mutant and isogenic wild-type (WT)-corrected CFBE41o- epithelial cells. RNA-sequencing was performed to compare Prevotella-induced signaling programs in WT-corrected versus CFTR mutant cells. Results: P. melaninogenica significantly reduced S. aureus lung infection, which was associated with elevated S. aureus killing by lung neutrophils and impaired S. aureus adherence to epithelial cells. Live or heat-killed Prevotella were sufficient to mediate these effects, which were dependent on the toll-like receptor TLR2. Prevotella impairment of S. aureus adherence also required CFTR function, as this effect was lost in CFTR mutant cells but restored by CFTR modulator therapy. RNA-sequencing identified several antibacterial defense pathways selectively upregulated by Prevotella in WT corrected epithelial cells, correlating with higher IL-8 and IL-6 cytokine production. Conclusions: P. melaninogenica enhanced neutrophil and epithelial defense against S. aureus, but these benefits were lost with CFTR dysfunction. CFTR modulator therapy rescued Prevotella responsiveness in respiratory epithelial cells, highlighting the potential for synergistic effects of host-microbiome interactions and CFTR targeted therapies.
Project description:We performed shotgun proteomics on the bacteria Prevotella brevis GA33 and Prevotella ruminicola 23. We did this for two types of samples (cell extract and cell membrane) and using two methods (data-dependent and data-independent acquisition).
Project description:Background: Recurrent implantation failure poses a challenge in assisted reproductive technology, often linked to an imbalance in the endometrial microbiome. Prevotella disiens, a bacterium found in the reproductive tract, is associated with reduced implantation success, but its effects on the endometrium are not well understood. This study uses hormone-responsive endometrial organoids to explore how Prevotella disiens alters endometrial function at a molecular level, aiming to uncover mechanisms contributing to implantation failure. Results: Endometrial organoids exposed to Prevotella disiens showed structural damage and significant changes in gene expression, unlike those treated with Lactobacillus species. Key findings include activation of the p38 MAPK pathway, suppression of WNT signaling, and increased expression of tryptophan metabolism genes. Metabolomic analysis revealed elevated kynurenine pathway metabolites in these organoids. Additionally, higher p38 MAPK and kynurenine pathway gene expression, and lower WNT pathway gene expression were observed in endometrial biopsies from patients with Prevotella disiens colonization. Blocking p38 MAPK in endometrial organoids reversed WNT suppression and normalized tryptophan metabolites. Conclusions: Prevotella disiens disrupts endometrial function by activating p38 MAPK, which inhibits WNT signaling and alters tryptophan metabolism, potentially hindering embryo implantation. These findings highlight the endometrial microbiome’s influence on reproductive success and point to p38 MAPK as a possible target for improving outcomes in assisted reproductive technology.
Project description:The transcriptional responses of Prevotella ruminicola were determined during growth on 20 different carbohydrate sources including mono-, di- and tri- saccharides, oligosaccharides, polymeric xylan and complete plant material with the aim of obtaining a more complete understanding of the number of genes and metabolic networks associated with carbohydrate catabolism by this organism All microarray hybridizations and subsequent scanning was undertaken using a two colour system (Cy3 and Cy5): 34 samples
Project description:Prevotella bryantii B14 was cultivated with monensin. Growth was monitored over a period of 9h with a broad range of monensin concentrations.