A Novel LysR Transcriptional Regulator in Burkholderia pseudomallei: Insights from Transcriptomic and Functional Analyses
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ABSTRACT:
ORGANISM(S): Burkholderia pseudomallei
PROVIDER: GSE302379 | GEO | 2025/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:Burkholderia pseudomallei is a soil-dwelling bacterium which has to survive not only under harsh environmental conditions, but also within various hosts where it can cause the infectious disease melioidosis. The ability, to quickly adapt to these different conditions, is based on its huge genome which encodes for complex regulatory networks. Among them are more than 60 genes belonging to the group of LysR-type transcriptional regulators (LTTRs). Here we analyzed a B. pseudomallei mutant harboring a transposon in the gene BPSL0117 annotated as a LTTR, which we named gvmR (globally acting virulence and metabolism regulator). The gvmR mutant displayed a growth defect in minimal medium and macrophages in comparison with the wild type. Moreover, inactivation of GvmR rendered B. pseudomallei avirulent in mice indicating a critical role of GvmR in infection. These defects of the mutant were rescued by ectopic expression of gvmR. To identify genes whose expression is modulated by GvmR, global transcriptome analysis of the B. pseudomallei wild type and gvmR mutant was performed using whole genome tiling microarrays. Transcript levels of 190 and 142 genes were found to be up- and downregulated in the gvmR mutant relative to the wild type. Among the most downregulated genes in the gvmR mutant were important virulence factor genes (T3SS3, T6SS1 and T6SS2), which might provide an explanation for the virulence defect of the gvmR mutant. In addition, expression of genes related to amino acid synthesis, glyoxylate shunt, iron-sulfur cluster assambly and syrbactin metabolism (secondary metabolite) was decreased in the mutant. Furthermore, inactivation of GvmR increased expression of genes involved in pyruvate metabolism, ATP synthesis, malleobactin and porin genes. Quantitative RT-PCR verified the differential expression of 27 selected genes. In summary, our data show that GvmR acts as an activating and repressing global regulator that is required to coordinate expression of a diverse set of metabolic and virulence genes for survival in the animal host and under nutrient limitation.
2018-05-02 | GSE110883 | GEO
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: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:LysR-type transcriptional regulators (LTTRs) are emerging as key circuit components in regulating microbial stress responses and are implicated in modulating oxidative stress in the human opportunistic pathogen Pseudomonas aeruginosa. The oxidative stress response encapsulates several strategies to overcome the deleterious effects of reactive oxygen species. However, many of the regulatory components and associated molecular mechanisms underpinning this key adaptive response remain to be characterised. Comparative analysis of publically available transcriptomic datasets led to the identification of a novel LTTR, PA2206, whose expression was altered in response to a range of host signals in addition to oxidative stress. PA2206 was found to be required for tolerance to H2O2 in vitro and lethality in vivo in the Zebrafish embryo model of infection. Transcriptomic analysis in the presence of H2O2 showed that PA2206 altered the expression of 58 genes, including a large repertoire of oxidative stress and iron responsive genes, independent of the master regulator of oxidative stress, OxyR. Contrary to the classic mechanism of LysR regulation, PA2206 did not autoregulate its own expression and did not influence expression of adjacent or divergently transcribed genes. The PA2214-15 operon was identified as a direct target of PA2206 with truncated promoter fragments revealing binding to the 5M-bM-^@M-^Y-ATTGCCTGGGGTTAT-3M-bM-^@M-^Y LysR box adjacent to the predicted -35 region. PA2206 also interacted with the pvdS promoter suggesting a global dimension to the PA2206 regulon, and suggests PA2206 is an important regulatory component of P. aeruginosa adaptation during oxidative stress. Six samples were analysed in total, three biological replicates of the PA2206 mutant and PA2206 complemented strains. Each biological replicate included three technical replicates.
2013-01-01 | E-GEOD-23367 | biostudies-arrayexpress
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: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:LysR-type transcriptional regulators (LTTRs) are the most common family of transcriptional regulators found in the opportunistic pathogen Pseudomonas aeruginosa. They are known to regulate a wide variety of virulence determinants and have emerged recently as positive global regulators of pathogenicity in a broad spectrum of serious bacterial pathogens. However, in spite of their key role in modulating expression of key virulence determinants underpinning pathogenic traits associated with the process of infection, surprisingly few were found to be transcriptionally altered in co-culture with host cells. bvlR (PA14_26880) an LTTR of previously unknown function, has been shown to be induced in response to host cells, and was therefore investigated for its potential role in virulence. BvlR expression was found to play a pivotal role in regulation of acute virulence determinants such as type III secretion and exotoxin A production. In contrast, loss of bvlR led to an inability to form tight microcolonies, a key step in biofilm formation in the mucoid lung, although surface attachment was increased. bvlR was also seen to a key role in P.aeruginosa pathogenicity within the acute model of infection, Caenorhabditis elegans. Unusually for LTTRs, BvlR was shown to exert its influence exclusively through the transcriptional repression of 307 genes, including the divergently transcribed gene bvlA. This highlights the importance of BvlR as a previously uncharacterized global virulence regulator in P. aeruginosa with a key role in the transcriptional response underlying the host pathogen interaction. Six samples were analysed in total, three biological replicates of the bvlR mutant and bvlR complemented strains.
2014-12-10 | E-GEOD-51491 | biostudies-arrayexpress
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.
2010-05-31 | GSE7577 | GEO
Project description:LysR-type transcriptional regulators (LTTRs) are emerging as key circuit components in regulating microbial stress responses and are implicated in modulating oxidative stress in the human opportunistic pathogen Pseudomonas aeruginosa. The oxidative stress response encapsulates several strategies to overcome the deleterious effects of reactive oxygen species. However, many of the regulatory components and associated molecular mechanisms underpinning this key adaptive response remain to be characterised. Comparative analysis of publically available transcriptomic datasets led to the identification of a novel LTTR, PA2206, whose expression was altered in response to a range of host signals in addition to oxidative stress. PA2206 was found to be required for tolerance to H2O2 in vitro and lethality in vivo in the Zebrafish embryo model of infection. Transcriptomic analysis in the presence of H2O2 showed that PA2206 altered the expression of 58 genes, including a large repertoire of oxidative stress and iron responsive genes, independent of the master regulator of oxidative stress, OxyR. Contrary to the classic mechanism of LysR regulation, PA2206 did not autoregulate its own expression and did not influence expression of adjacent or divergently transcribed genes. The PA2214-15 operon was identified as a direct target of PA2206 with truncated promoter fragments revealing binding to the 5’-ATTGCCTGGGGTTAT-3’ LysR box adjacent to the predicted -35 region. PA2206 also interacted with the pvdS promoter suggesting a global dimension to the PA2206 regulon, and suggests PA2206 is an important regulatory component of P. aeruginosa adaptation during oxidative stress.
2013-01-01 | GSE23367 | GEO