Project description:Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a disease endemic to South-East Asia and Northern Australia. Clinical presentation is highly variable, ranging from asymptomatic to fatal septicaemia, and thus the outcome of infection can depend on the host immune responses. The aim of this study was to characterise the macrophage immune response to B. pseudomallei in the presence of novel inhibitors targeting the virulence factor, Macrophage Infectivity Potentiator (Mip) protein. To do this. murine macrophage J774A.1 cells were infected with B. pseudomallei K96243 in the presence and absence of two small-molecule inhibitors designed to target the Mip protein. Global transcriptional profiling of macrophages infected with B. pseudomallei was analysed by RNA-Seq four hours post-infection. In the presence of Mip inhibitors, we found a significant reduction in the expression of pro-inflammatory cytokines highlighting the potential to utilize Mip inhibitors to dampen potentially harmful pro-inflammatory responses resulting from B. pseudomallei infection in macrophages. We then performed gene expression profiling analysis using data obtained from RNA-seq of J774A.1 macrophages infected with Burkholderia pseudomallei in the presence of two Mip inhibitors or vehicle control 4 hours post-infection
Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of DNA methylations in Burkholderia pseudomallei.
Project description:Burkholderia pseudomallei can adapt to and thrive in a variety of environments, including soil and water, and also can infect different hosts, including humans, leading to the tropical disease melioidosis. Modulation of gene and protein expression is one of this pathogen's adaptive survival mechanisms, which could lead to changes in the bacteria's cell membrane, metabolism, and virulence. To better understand bacterial adaptation and host-pathogen interactions, this study compared the expression profiles of B. pseudomallei from infected mice to B. pseudomallei cultivated in soil extract media. B. pseudomallei in vivo was created by infecting mice through the intraperitoneal route and harvesting the spleens on day 5 post infection. Total RNA was isolated and sequenced from the harvested spleen. Sequence reads were mapped to the B. pseudomallei UKMD286 strain genome sequence.
Project description:We report the methylome sequencing and annotation of Burkholderia pseudomallei D286 based on high-throughput profiling using PacBio SMRT technology
Project description:Burkholderia pseudomallei is the causative agent of melioidosis a disease endemic in South-East Asia and Northern Australia. The mortality rates in these areas are unacceptably high even with antibiotic treatment, attributed to intrinsic and acquired resistance of B. pseudomallei to antibiotics. With very few options for therapeutics there is an urgent requirement to identify anti-bacterial targets for the development of novel, effective treatments. In this study we examine the role and effect of ppiB on the proteome. Using LFQ analysis we show loss of ppiB has dramatic effect on the Burkholderia pseudomallei proteome.
Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of DNA methylations in Burkholderia pseudomallei. SMRTbell™ sequencing
Project description:Transcriptional profiling of mouse macrophage cells comparing control untreated cells with macrophage cells infected with Burkeholderia pseudomallei. Goal was to determine the effects of bacterial infection on global macrophage gene expression.
Project description:This study reports the expression profile of intracellular B. pseudomallei following infection of human macrophage-like U937 cells. The transcriptome of intracellular B. pseudomallei harvested from macrophage cells over an infection period of 6 hr (1, 2, 4 and 6 hr post-infection) were compared to in vitro grown bacteria to identify genes whose expression is altered in response to intracellular growth.
Project description:Gene expression profiles of human cell (THP-1) lines exposed to a novel Daboiatoxin (DbTx) isolated from Daboia russelli russelli, and specific cytokines and inflammatory pathways involved in acute infection caused by Burkholderia pseudomallei. Keywords: Melioidosis, Burkholderia pseudomallei, Daboiatoxin, Cytokines, Inflammation.
