Toxicogenomic Effect of Burkholderia pseudomallei in a Human Macrophage Cell (THP-1) Model of Acute Melioidosis Using Whole-genome Microarray
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ABSTRACT:
ORGANISM(S): Homo sapiens Burkholderia pseudomallei
PROVIDER: GSE7577 | GEO | 2010/05/31
SECONDARY ACCESSION(S): PRJNA100355
REPOSITORIES: GEO
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Project description:Melioidosis is a neglected tropical disease caused by the Gram-negative bacterium Burkholderia pseudomallei. It is widespread in Southeast Asia and under-reported across tropical regions worldwide. Patients present with a range of clinical syndromes including sepsis, pneumonia and focal abscesses, with a mortality rate of 40% in hospitalized patients in Thailand. Up to two-thirds of patients with melioidosis have diabetes mellitus. In this experiment we sought to characterize pathways activated by whole killed B. pseudomallei bacteria and by three vaccine candidate proteins from B. pseudomallei, BPSL2520 (uncharacterized protein), BPSS1525 (BopE) and BPSL2096 (AhpC) in patients with diabetes and acute melioidosis.
2017-09-22 | E-MTAB-6093 | biostudies-arrayexpress
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.
2019-08-05 | PXD012956 | Pride
Project description:Bacterial transcriptomes are dynamic, context-specific and condition-dependent. Infection by the soil bacterium, Burkholderia pseudomallei, causes melioidosis, an often fatal infectious disease of humans and animals. Possessing a large multi-chromosomal genome, B. pseudomallei is able to persist and survive in a multitude of environments. To obtain a comprehensive overview of B. pseudomallei expressed transcripts, we initiated whole-genome transcriptome profiling covering a broad spectrum of conditions and exposures – a so-called “condition compendium”. Using the compendium, we confirmed many previously-annotated genes and operons, and also identified hundreds of novel transcripts including anti-sense transcripts and non-coding RNAs. By systematically examining genes exhibiting highly similar expression patterns, we ascribed putative functions to previously uncharacterized genes, and identified novel regulatory elements controlling these expression patterns. We also used the compendium to elucidate candidate virulence pathways associated with quorum-sensing and infection in mice. Our study showcases the power of a B. pseudomallei condition compendium as a valuable resource for understanding microbial physiology and the pathogenesis of melioidosis.
2013-09-12 | GSE43205 | GEO
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
2024-03-06 | GSE244127 | GEO
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. Experiment Overall Design: 1. Group I:- Human monocytic macrophage (THP-1) cell lines grown in the culture medium without any bacterial infection served as untreated control group (Three Biological Replicates). Experiment Overall Design: 2. Group II:- THP-1 cells were infected with Burkholderia pseudomallei (A600 nm = OD 0.6, ~5 x 107 cfu/ml) for 24h served as a disease control group (Three Biological Replicates). Experiment Overall Design: 3. Group III:- THP-1 cells were infected with B. pseudomallei and treated with Daboiatoxin (0.5 mM) isolated from Daboia russelli russelli venom served as a treatment group (Three Biological Replicates). Experiment Overall Design: 4. Group IV:- THP-1 cells were infected with B. pseudomallei (A600 nm = OD 0.6, ~5 x 107 cfu/ml) treated with standard antimicrobial drug ceftazidime (10mg/ml) served as a drug control (Three Biological Replicates). Experiment Overall Design: 5. Group V:- THP-1 cells were exposed to Daboiatoxin (0.5 mM) without bacterial infection (Three Biological Replicates).
2009-04-04 | E-GEOD-7577 | biostudies-arrayexpress
Project description:Burkholderia mallei and Burkholderia pseudomallei are both potential biological threats agents. Melioidosis caused by B. pseudomallei is endemic in Southeast Asia and Northern Australia, while glanders caused by B. mallei infections are rare. Here we studied the proteomes of different B. mallei and B. pseudomallei isolates to determine species specific characteristics. Analyzing the expressed proteomes of B. mallei and B. pseudomallei revealed differences between B. mallei and B. pseudomallei but also between isolates from the same species. Expression of multiple virulence factors and proteins of several PKS/NRPS clusters was demonstrated. Proteome analysis can be used not only to identify bacteria but also to characterize the expression of important factors that putatively contribute to pathogenesis of B. mallei and B. pseudomallei.
2022-12-15 | PXD028126 | Pride
Project description:Bacterial transcriptomes are dynamic, context-specific and condition-dependent. Infection by the soil bacterium, Burkholderia pseudomallei, causes melioidosis, an often fatal infectious disease of humans and animals. Possessing a large multi-chromosomal genome, B. pseudomallei is able to persist and survive in a multitude of environments. To obtain a comprehensive overview of B. pseudomallei expressed transcripts, we initiated whole-genome transcriptome profiling covering a broad spectrum of conditions and exposures M-bM-^@M-^S a so-called M-bM-^@M-^\condition compendiumM-bM-^@M-^]. Using the compendium, we confirmed many previously-annotated genes and operons, and also identified hundreds of novel transcripts including anti-sense transcripts and non-coding RNAs. By systematically examining genes exhibiting highly similar expression patterns, we ascribed putative functions to previously uncharacterized genes, and identified novel regulatory elements controlling these expression patterns. We also used the compendium to elucidate candidate virulence pathways associated with quorum-sensing and infection in mice. Our study showcases the power of a B. pseudomallei condition compendium as a valuable resource for understanding microbial physiology and the pathogenesis of melioidosis. The transcriptome profiles of Bp exposed to 82 conditions were captured using a custom-designed tiling microarray and compiled into a compendium revealing novel genomic features and co-expression network.
2013-09-12 | E-GEOD-43205 | biostudies-arrayexpress
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.
2022-07-22 | E-MTAB-11200 | biostudies-arrayexpress
Project description:Burkholderia pseudomallei - Multistate Melioidosis 2021
| PRJNA763213 | ENA
Project description:Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicaemia to chronic localized illness or latent infection. Mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL10, TREM1 and IFN-signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including IL10, TREM1 and IFNsignaling, revealing the common immune response occurring in both mice and humans.
2015-09-02 | GSE61106 | GEO