Project description:Dictyostelium discoideum amoebae feed by ingesting bacteria, then killing them in phagosomes. Ingestion and killing of different bacteria have been shown to rely on largely different molecular mechanisms. One would thus expect that D. discoideum adapts its ingestion and killing machinery when encountering different bacteria. In this study, we investigated by RNA sequencing if and how D. discoideum amoebae respond to the presence of different bacteria by modifying their gene expression patterns. Each bacterial species analyzed induced a specific modification of the transcriptome. Bacteria such as Bacillus subtilis, Klebsiella pneumoniae, or Mycobacterium marinum induced a specific and different transcriptional response, while Micrococcus luteus did not trigger a significant gene regulation. Although folate has been proposed to be one of the key molecules secreted by bacteria and recognized by hunting amoebae, it elicited a very specific and restricted transcriptional signature, distinct from that triggered by any bacteria analyzed here. Our results indicate that D. discoideum amoebae respond in a highly specific, almost non-overlapping manner to different species of bacteria. We additionally identify specific sets of genes that can be used as reporters of the response of D. discoideum to different bacteria.
Project description:The association between colorectal cancer (CRC) clinical variables and Fusobacterium, but not other intra-tumoral bacteria, has been extensively studied. Here we leveraged whole-transcriptome sequencing from 807 CRC tumor samples from the AVANT phase III trial to dually characterize tumor gene expression and intra-tumoral bacteria. After stringent filtering, 74 high-confidence taxa were identified. 17 of these species, including 4 Fusobacterium spp., were classified as orally-derived and had a robust signal within right-sided, MSI-H, and BRAF mutant tumors. Across consensus molecular subtypes (CMS), integration of Fusobacterium animalis presence and tumor gene expression revealed that F. animalis had the greatest number of associations in mesenchymal CMS4 tumors, despite an overall lower prevalence than in immune CMS1 tumors. Pathway analysis within CMS4 revealed that F. animalis, but not other highly prevalent species, was uniquely associated with pathways for collagen degradation and formation as well as IL-6 and IL-1 cytokine signaling. These associations could explain in part why Fusobacterium has been previously associated with reduced survival in mesenchymal populations. Overall, this study identified oral-derived bacteria, including Fusobacterium, as broadly more prevalent in inflamed CRC tumors compared to the other subtypes, and the association of intra-tumoral bacteria on tumor gene expression is context- and species-specific.
Project description:To better understand the impact of infection on oocyte quality we employed global transcriptomics of oocytes collected from heifers after receiving intrauterine infusion of pathogenic Escherichia coli and Trueperella pyogenes. We hypothesized that oocyte transcriptome would be altered in response to intrauterine infection. A total of 452 differentially expressed genes were identified in oocytes collected from heifers 4 days after bacteria infusion compared to vehicle infusion, while 539 differentially expressed genes were identified in oocytes collected from heifers 60 days after bacteria infusion. Only 42 genes were differentially expressed in bacteria infused heifers at both day 4 and day 60. Interferon, HMGB1, ILK, IL-6 and TGF-beta signaling pathways were downregulated in oocytes collected at day 4 from bacteria infused heifers, while interferon, ILK and IL-6 signaling were upregulated in oocytes collected at day 60 from bacteria infused heifers. These data suggest that bacterial infusion alters the oocyte transcriptome differently at day 4 and day 60, suggesting different follicle stages are susceptible to damage. Characterizing the long-term impacts of uterine infection on oocyte transcriptome aids in our understanding of how infection causes infertility in dairy cattle.