Regulation of Salmonella typhimurium plasmid encoded fimbriae

Bacteria interact with their environment through proteinacious fibers known as fimbriae. Fimbrial expression is regulated in response to environmental stimuli. Some fimbriae undergo phase variation, which results in a population of bacteria skewed between fimbrial expression (phase ON) and non-expression (phase OFF) under inducing conditions. Transcriptional phase variation can be regulated by methylation of GATC DNA sequences, which are targets of DNA adenine methylase (Dam). This dissertation investigates the regulation and phase variation of Salmonella typhimurium plasmid encoded fimbriae (pef). The Pef operon shares features with the E. coli pyleonephritis associated pilus (pap) operon, which is regulated by a methylation dependent transcriptional switch. Expression of Pef fimbriae was induced in standing culture at low pH (pH 5.1). Transcription of pef was dependent on Leucine responsive regulatory protein (Lrp) and DNA adenine methylase (Dam). Lrp was essential for methylation protection of the pef GATC sites. Based on genetic analyses, methylation of GATC II was necessary for activation of pef transcription. Expression of the pef operon was inhibited by the histone like protein (H-NS) and the stationary phase sigma factor (RpoS). The pef operon is the first example of methylation dependent fimbrial regulation outside of E. coli.