In Salmonella enterica, the pathogenicity island 2 (SPI-2) regulator PagR regulates its own expression and the expression of a five-gene operon that encodes transketolase C

Mol Microbiol. 2023 Oct;120(4):575-586. doi: 10.1111/mmi.15143. Epub 2023 Aug 24.


The enteropathogen Salmonella enterica subsp. enterica sv. Typhimurium str. LT2 (hereafter S. Typhimurium) utilizes a cluster of genes encoded within the pathogenicity island 2 (SPI-2) of its genome to proliferate inside macrophages. The expression of SPI-2 is controlled by a complex network of transcriptional regulators and environmental cues, which now include a recently characterized DNA-binding protein named PagR. Growth of S. Typhimurium in low-phosphate, low-magnesium medium mimics conditions inside macrophages. Under such conditions, PagR ensures SPI-2 induction by upregulating the transcription of slyA, which encodes a known activator of SPI-2. Here, we report that PagR represses the expression of a divergently transcribed polycistronic operon that encodes the two subunits of transketolase TktC (i.e., tktD, tktE) of this bacterium. Transketolases contribute to the nonredox rearrangements of phosphorylated sugars of the pentose phosphate pathway, which provide building blocks for amino acids, nucleotides, cofactors, etc. We also demonstrate that PagR represses the expression of its own gene and define two PagR-binding sites between stm2344 and pagR.

Keywords: PagR protein; Salmonella pathogenesis; pagR gene expression; pentose phosphate pathway; tktDE expression; transcriptional regulation; transketolase.