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Gene expression profiling of Salmonella enterica serovar Typhimurium exposed to subinhibitory concentrations of fosmidomycin and kanamycin

ABSTRACT: Expression profiling on a total of 4,391 genes was conducted to identify regulated S. typhimurium genes upon exposure to subinhibitory concentrations of the MEP pathway antibiotic fosmidomycin. These results were subsequently compared to a similar gene expression analysis of subinhibitory exposures of S. typhimurium to the bactericide kanamycin

ORGANISM(S): Salmonella enterica subsp. enterica serovar Typhimurium str. LT2

PROVIDER: GSE50480 | GEO | 2016/08/28

SECONDARY ACCESSION(S): PRJNA217712

REPOSITORIES: GEO

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Project description:InvF ChIP-chip on Salmonella enterica serovar Typhimurium SL1344 using anti-Myc antibody against strain with chromosomally 9Myc-tagged InvF (IP samples) and wildtype strain (mock IP samples) Salmonella enterica serovar Typhimurium causes a range of diseases from self-limiting gastroenteritis to life-threatening systemic infections. Its complex infection process is initiated by the invasion of the intestinal epithelial monolayer by means of a type three secretion system. InvF is one of the key regulators governing the invasion of epithelial cells. By mapping the InvF regulon, i.e. locating its direct target genes, the gene network underlying invasion can be further examined, including identifying possible new effector-encoding genes. In order to map the InvF regulon, we performed chromatin immunoprecipitation combined with tiling microarray analysis (ChIP-chip) and compared expression of the identified target genes in an invF mutant and a wildtype strain. In addition, the promoter regions of these target genes were searched for the presence of an InvF recognition site. Finally, a query-driven biclustering method, combined with a microarray compendium containing publically available S. Typhimurium gene expression data, was applied as an in silico validation technique for functional relatedness between newly identified target genes and known invasion genes. As expected, under invasion inducing conditions, InvF activates the expression of invasion chaperone encoding sicA and the effector-encoding genes sopB, sopE, sopE2 and sopA by binding their promoter region. Newly identified InvF targets are steB, encoding a secreted effector, and STM1239. The presence of an InvF recognition site in the promoter regions of these target genes further supports this observation. In addition, the query-driven biclustering method revealed similarities in expression profiles between STM1239 and known InvF regulated invasion genes over a range of experimental conditions. In conclusion, we here deliver the first evidence for direct binding of InvF to the promoter regions of sopA and sopE2, and associate genes encoding a secreted effector (steB) and a putative novel effector (STM1239) with the Salmonella invasion regulator InvF.

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Gene expression profiling of Salmonella enterica serovar Typhimurium exposed to subinhibitory concentrations of fosmidomycin and kanamycin

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