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DNA Adenine Methylation Regulates Virulence Gene Expression in Salmonella enterica Serovar Typhimurium

Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41080 Seville, Spain,¹ Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, United Kingdom,² Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain³

Received 14 June 2006/ Accepted 6 September 2006

Transcriptomic analyses during growth in Luria-Bertani medium were performed in strain SL1344 of Salmonella enterica serovar Typhimurium and in two isogenic derivatives lacking Dam methylase. More genes were repressed than were activated by Dam methylation (139 versus 37). Key genes that were differentially regulated by Dam methylation were verified independently. The largest classes of Dam-repressed genes included genes belonging to the SOS regulon, as previously described in Escherichia coli, and genes of the SOS-inducible Salmonella prophages ST64B, Gifsy-1, and Fels-2. Dam-dependent virulence-related genes were also identified. Invasion genes in pathogenicity island SPI-1 were activated by Dam methylation, while the fimbrial operon std was repressed by Dam methylation. Certain flagellar genes were repressed by Dam methylation, and Dam^– mutants of S. enterica showed reduced motility. Altered expression patterns in the absence of Dam methylation were also found for the chemotaxis genes cheR (repressed by Dam) and STM3216 (activated by Dam) and for the Braun lipoprotein gene, lppB (activated by Dam). The requirement for DNA adenine methylation in the regulation of specific virulence genes suggests that certain defects of Salmonella Dam^– mutants in the mouse model may be caused by altered patterns of gene expression.

Published ahead of print on 22 September 2006.

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