Biophysical Society Thematic Meeting

Mechanobiology of Disease

Thursday Speaker Abstracts

SsrB as a Driver of Lifestyle Changes in Salmonellae

Stuti K. Desai

, Linda J. Kenney

1,2,3

Mechanobiology Institute, National University of Singapore, Singapore,

University of Illinois-

Chicago, Chicago, IL, USA,

Jesse Brown VAMC, Chicago, IL, USA.

SsrA/B is a two-component signaling system in Salmonella enterica that is encoded on one of the

horizontally acquired AT-rich segments of the genome called Salmonella Pathogenecity Island-2

(SPI-2). It is essential for the successful existence of serovars Typhi and Typhimurium inside

host cells and is absent in the nearest phylogenetic neighbor, S. bongori. In response to

environmental stimuli such as changes in pH and osmolality, transcriptional activation of SPI-2

by SsrB~P regulates the intracellular lifestyle of Salmonella. However, for successful

pathogenesis in terms of carriage and persistence, Salmonella exists as multicellular

communities. We recently found that this sessile lifestyle was also regulated by SsrB. SsrB

activated the expression of the master regulator of biofilm formation, csgD (agfD), in the

absence of any phosphate donors, including SsrA. This was achieved by relieving transcriptional

silencing by H-NS at the csgD regulatory region. Atomic force microscopy revealed that the full-

length unphosphorylated SsrB was bound to the upstream regulatory region of csgD, in

agreement with our genetic and biochemical results. This binding and subsequent changes in the

local DNA topology was sufficient to partially drive off H-NS and activate csgD expression. In

contrast, SsrB~P regulates expression of the SPI-2 regulon by both direct transcriptional

activation and anti-silencing. Our findings unravelled a novel role for unphosphorylated SsrB in

regulating gene expression and established the mechanism by which anti-silencing occured.

Therefore, depending on its phosphorylation state, SsrB, assists Salmonella Typhimurium to

decide its lifestyle choice: intracellular versus the carrier state or biofilms. Building on this

paradigm, we are now studying the larger role of SsrB and SsrB~P in regulating enivronmentally

sensitive genes as Salmonella alternates between the two lifestyles. Deciphering the SsrB versus

SsrB~P regulons in Typhimurium will also help to understand the carrier state of Typhi.