Identification of the regulatory logic controlling Salmonella pathoadaptation by the SsrA-SsrB two-component system

• Published in: PLoS genetics 2010-03, Vol.6 (3), p.e1000875-e1000875
• Main Authors: Tomljenovic-Berube, Ana M, Mulder, David T, Whiteside, Matthew D, Brinkman, Fiona S L, Coombes, Brian K
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - genetics; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Base Sequence; Chromatin Immunoprecipitation; Conserved Sequence; DNA sequencing; DNA, Bacterial - metabolism; Evolution, Molecular; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genetic aspects; Genetic Loci - genetics; Genetic regulation; Genetics and Genomics/Gene Discovery; Genetics and Genomics/Gene Expression; Genetics and Genomics/Microbial Evolution and Genomics; Genome, Bacterial - genetics; Genomic Islands - genetics; Genomics; Infectious Diseases; Inverted Repeat Sequences - genetics; Medical research; Methods; Molecular Sequence Data; Mutation; Mutation - genetics; Noncoding DNA; Nucleotide sequencing; Oligonucleotide Array Sequence Analysis; Operon - genetics; Promoter Regions, Genetic - genetics; Properties; Protein Binding; Proteins; Regulon - genetics; RNA, Bacterial - genetics; RNA, Bacterial - metabolism; Salmonella; Salmonella - genetics; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000875

Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world. Regulatory evolution, in which non-coding DNA is mutated to create new regulatory nodes, also contributes to this diversity to allow niche adaptation and the evolution of pathogenesis. To survive in the host environment, Salmonella enterica uses a type III secretion system and effector proteins, which are activated by the SsrA-SsrB two-component system in response to the host environment. To better understand the phenomenon of regulatory evolution in S. enterica, we defined the SsrB regulon and asked how this transcription factor interacts with the cis-regulatory region of target genes. Using ChIP-on-chip, cDNA hybridization, and comparative genomics analyses, we describe the SsrB-dependent regulon of ancestral and horizontally acquired genes. Further, we used a genetic screen and computational analyses integrating experimental data from S. enterica and sequence data from an orthologous regulatory system in the insect endosymbiont, Sodalis glossinidius, to identify the conserved yet flexible palindrome sequence that defines DNA recognition by SsrB. Mutational analysis of a representative promoter validated this palindrome as the minimal architecture needed for regulatory input by SsrB. These data provide a high-resolution map of a regulatory network and the underlying logic enabling pathogen adaptation to a host.