GvmR – A Novel LysR-Type Transcriptional Regulator Involved in Virulence and Primary and Secondary Metabolism of Burkholderia pseudomallei

Abstract

<i>Burkholderia pseudomallei</i> is a soil-dwelling bacterium able to survive not only under adverse environmental conditions, but also within various hosts which can lead to the disease melioidosis. The capability of <i>B. pseudomallei</i> to adapt to environmental changes is facilitated by the large number of regulatory proteins encoded by its genome. Among them are more than 60 uncharacterized LysR-type transcriptional regulators (LTTRs). Here we analyzed a <i>B. pseudomallei</i> mutant harboring a transposon in the gene BPSL0117 annotated as a LTTR, which we named <i>gvmR</i> (globally acting virulence and metabolism regulator). The <i>gvmR</i> mutant displayed a growth defect in minimal medium and macrophages in comparison with the wild type. Moreover, disruption of <i>gvmR</i> rendered <i>B. pseudomallei</i> avirulent in mice indicating a critical role of GvmR in infection. These defects of the mutant were rescued by ectopic expression of <i>gvmR</i>. To identify genes whose expression is modulated by GvmR, global transcriptome analysis of the <i>B. pseudomallei</i> wild type and <i>gvmR</i> mutant was performed using whole genome tiling microarrays. Transcript levels of 190 genes were upregulated and 141 genes were downregulated in the <i>gvmR</i> mutant relative to the wild type. Among the most downregulated genes in the <i>gvmR</i> mutant were important virulence factor genes (T3SS3, T6SS1, and T6SS2), which could explain the virulence defect of the <i>gvmR</i> mutant. In addition, expression of genes related to amino acid synthesis, glyoxylate shunt, iron-sulfur cluster assembly, and syrbactin metabolism (secondary metabolite) was decreased in the mutant. On the other hand, inactivation of GvmR increased expression of genes involved in pyruvate metabolism, ATP synthesis, malleobactin, and porin genes. Quantitative real-time 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 essential for the survival in the animal host and under nutrient limitation.