Oral Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

To P~ or not to P~: Unphosphorylated SsrB activates csgD (agfD) to regulate Salmonella Typhimurium biofilms (#14)

Stuti K. Desai 1 , Linda J. Kenney 1 2 3
  1. National University of Singapore, Singapore
  2. Jesse Brown Veterans Administration Medical Center, Chicago, IL, United States
  3. University of Illinois-Chicago, Chicago, IL, United States

Salmonella can adopt two distinct lifestyles in the host: during systemic infection, it exists inside macrophages in a Salmonella-containing vacuole. In the carrier state, Salmonella forms biofilms on gallstones in the gall bladder. In the present work, we demonstrate that SsrB, a pathogenicity island (i.e. non-ancestral) encoded regulator determines the switch between these two lifestyles by the control of ancestral genes. In the acidic macrophage vacuole, the kinase SsrA is expressed via activation of the ancestral EnvZ/OmpR two-component system. SsrA phosphorylates SsrB, and SsrB~P relieves silencing of virulence genes and activates their transcription. Remarkably, in the absence of SsrA, unphosphorylated SsrB activates csgD (agfD), the master regulator of biofilm formation. Presently, we unambiguously reveal a negative role for H-NS in regulating csgD. We demonstrate by atomic force microscopy that SsrB binds to the upstream regulatory region of csgD and disrupts the silenced H-NS-bound promoter. Although SsrB is located on Salmonella pathogenicity island 2 and was acquired by horizontal gene transfer, it controls ancestral genes by anti-silencing to switch between these two opposing lifestyles. Supported by the Research Center of Excellence in Mechanobiology from the Ministry of Education, Singapore and VA 5I01BX000372 to LJK.