title: The horizontally-acquired response regulator SsrB drives a Salmonella lifestyle switch by relieving biofilm silencing.
abstract: A common strategy by which bacterial pathogens reside in humans is by shifting from a virulent lifestyle, (systemic infection), to a dormant carrier state. Two major serovars of Salmonella enterica, Typhi and Typhimurium, have evolved a two-component regulatory system to exist inside Salmonella-containing vacuoles in the macrophage, as well as to persist as asymptomatic biofilms in the gallbladder. Here we present evidence that SsrB, a transcriptional regulator encoded on the SPI-2 pathogenicity-island, determines the switch between these two lifestyles by controlling ancestral and horizontally-acquired genes. In the acidic macrophage vacuole, the kinase SsrA phosphorylates SsrB, and SsrB~P relieves silencing of virulence genes and activates their transcription. In the absence of SsrA, unphosphorylated SsrB directs transcription of factors required for biofilm formation specifically by activating csgD (agfD), the master biofilm regulator by disrupting the silenced, H-NS-bound promoter. Anti-silencing mechanisms thus control the switch between opposing lifestyles.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, Singapore.
authors.forename: Stuti K
authors.initials: SK
authors.lastname: Desai
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, Singapore.|Department of Physics, National University of Singapore, Singapore, Singapore.
authors.forename: Ricksen S
authors.initials: RS
authors.lastname: Winardhi
authors.affiliation: Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Periasamy
authors.affiliation: Nanoscience and Nanotechnology Institute, National University of Singapore, Singapore, Singapore.|Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Michal M
authors.identifier: http://orcid.org/0000-0001-5933-314X
authors.initials: MM
authors.lastname: Dykas
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, Singapore.|Department of Physics, National University of Singapore, Singapore, Singapore.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jie
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, Singapore.|Jesse Brown Veterans Affairs Medical Center, University of Illinois-Chicago, Chicago, United States.|Department of Microbiology and Immunology, University of Illinois-Chicago, Chicago, United States.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Kenney
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D012486:Salmonella typhimurium / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C119761:SsrB protein, Salmonella typhimurium; D014157:Transcription Factors
keywords: CsgD/AgfD; H-NS; Salmonella Typhimurium; SsrA/B; biofilm; infectious disease; microbiology; two-component regulatory system