Project description:The mammalian immune system is constantly challenged by signals from both pathogenic and non-pathogenic microbes. Many of these non-pathogenic microbes have pathogenic potential if the immune system is compromised. The importance of type I interferons (IFNs) in orchestrating innate immune responses to pathogenic microbes has become clear in recent years. However, the control of opportunistic pathogens – and especially intracellular bacteria – by type I IFNs remains less appreciated. In this study, we use the opportunistic, Gram-negative bacterial pathogen Burkholderia cenocepacia (Bc) to show that type I IFNs are capable of limiting bacterial replication in macrophages, preventing illness in immunocompetent mice. Sustained type I IFN signaling through cytosolic receptors allows for increased expression of autophagy and linear ubiquitination mediators, which slows bacterial replication. Transcriptomic analyses and in vivo studies also show that LPS stimulation does not replicate the conditions of intracellular Gram-negative bacterial infection as it pertains to type I IFN stimulation or signaling. This study highlights the importance of type I IFNs in protection against opportunistic pathogens through innate immunity, without the need for damaging inflammatory responses.
2021-01-19 | GSE165020 | GEO
Project description:Deep Nanopore Q20+ sequencing of Zymo D6331
Project description:KSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
Project description:KSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
Project description:KSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
Project description:KSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
Project description:Ralstonia solanacearum causes disease in more than 200 plant species including bacterial wilt of tomatoes and brown rot of potatoes. This bacterium is a soilborne and waterborne pathogen, with a worldwide distribution and is on the EPPO A2 list of quarantine pathogens. ln the UK, the bacterium is present in the rivers, but its prevalence depends on the season; it is highly abundant in the summer and undetectable during winter. To survive the cold winter temperatures, R. solanacearum overwinters inside plants growing alongside the rivers such as Solanum dulcamara. Interestingly, this plant species doesn’t show bacterial wilt symptoms. To understand genomic differences with susceptible hosts, we assembled the genome using Oxford Nanopore Technologies and Illumina sequencing.
2025-04-09 | GSE262401 | GEO
Project description:Q20 nanopore long-read sequencing of isolates of Pseudomonas aeruginosa.
Project description:Post-transcriptional modification of tRNAs represents an essential layer of translational regulation critical for bacterial adaptation to environmental changes. Increasing evidence links the tRNA epitranscriptome to pivotal roles in the regulation of gene expression and various cellular processes, including stress responses and the establishment of virulence phenotypes. In this study, we used mass-spectrometry and nanopore sequencing to systematically identify and quantify sites of TrhPO-dependent tRNA hydroxylation in total and purified tRNAs in the opportunistic human pathogen Pseudomonas aeruginosa. Furthermore, transcriptomic, ribosome profiling and proteomic data were integrated to demonstrate the post-transcriptional consequences of the absence of xo5U modifications at wobble positions in selected tRNAs. We show that changes in metabolic fluxes drive the impaired ability to infect host cells and strongly attenuated virulence in the Galleria mellonella model. In the absence of TrhPO-mediated tRNA modification, chorismate, the precursor for the biosynthesis of xo5U-modifications, is funneled into alternative pathways including the production of aromatic amino acids and phenazines. Our findings that metabolic rerouting rather than changes in proteome profiles attenuates P. aeruginosa virulence highlights the multifunctional roles of tRNA-modifying enzymes and suggests an underexplored role for these enzymes in monitoring and modulating metabolic fitness. These insights open new avenues for combatting the pathogenicity of this challenging opportunistic pathogen.
