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Status |
Public on May 02, 2018 |
Title |
Identification of a novel LysR-type regulator involved in virulence and primary and secondary metabolism of Burkholderia pseudomallei. |
Platform organism |
Burkholderia pseudomallei K96243 |
Sample organism |
Burkholderia pseudomallei |
Experiment type |
Expression profiling by array
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Summary |
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.
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Overall design |
The transcriptome profiles of Burkholderia pseudomallei wild type strain E8 and corresponding transposon mutant strain (BPSL0117::Tn5) exposed to one growth condition (M9 minimal medium, exponential growth) were captured and compared using a custom-designed tiling microarray to elucidate the BPSL0117 dependent regulon. Three biological replicates per strain were used.
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Contributor(s) |
Kohler C |
Citation(s) |
29867844 |
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Submission date |
Feb 20, 2018 |
Last update date |
Aug 01, 2018 |
Contact name |
Christian Kohler |
E-mail(s) |
christian.kohler@med.uni-greifswald.de
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Organization name |
University Medicine Greifswald
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Department |
Friedrich Loeffler Institue of Medical Microbiology
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Street address |
Ferdinand Sauerbruch Strasse 1
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City |
Greifswald |
ZIP/Postal code |
17489 |
Country |
Germany |
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Platforms (1) |
GPL16432 |
NimbleGen Burkholderia pseudomallei K96243 385K tiling array [071211_BPK96243_CO_Tiling] |
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Samples (6)
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Relations |
BioProject |
PRJNA434734 |