The fis operon from Salmonella typhimurium has been cloned and sequenced, and the properties of Fisdeficient and Fis-constitutive strains were examined. The overall fis operon organization in S. typhimurium is the same as that in Escherichia coli, with the deduced Fis amino acid sequences being identical between both species. While the open reading frames upstream of fis have diverged slightly, the promoter regions between the two species are also identical between ؊49 and ؉94. Fis protein and mRNA levels fluctuated dramatically during the course of growth in batch cultures, peaking at ϳ40,000 dimers per cell in early exponential phase, and were undetectable after growth in stationary phase. fis autoregulation was less effective in S. typhimurium than that in E. coli, which can be correlated with the absence or reduced affinity of several Fis-binding sites in the S. typhimurium fis promoter region. Phenotypes of fis mutants include loss of Hin-mediated DNA inversion, cell filamentation, reduced growth rates in rich medium, and increased lag times when the mutants are subcultured after prolonged growth in stationary phase. On the other hand, cells constitutively expressing Fis exhibited normal logarithmic growth but showed a sharp reduction in survival during stationary phase. During the course of these studies, the 28 -dependent promoter within the hin-invertible segment that is responsible for fljB (H2) flagellin synthesis was precisely located.An increasing number of functions are being assigned to the Fis protein (factor for inversion stimulation) in Escherichia coli. Many of these functions have been associated with sitespecific DNA recombination events. Fis was first identified as a factor from E. coli that is required to stimulate site-specific DNA inversion reactions mediated by Salmonella typhimurium Hin (26), by Mu phage Gin (27), and by P1 phage Cin recombinases (20). Fis was also shown to stimulate phage DNA excision and integration (2, 3, 57), which is a mechanistically different DNA recombination reaction (8, 34). Fis also stimulates DNA excision in the case of the -like phage HK022 but, in addition, serves to repress a DNA inversion event upon establishment of lysogeny which would otherwise yield defective lysogens (10). Increased stability of and Mu lysogens is also observed in the presence of Fis (3, 5, 6). Even transposition frequencies of transposon Tn5 and insertion sequence IS50 are found to be influenced by Fis (60).Other functions of Fis are unrelated to specialized DNA recombination and may offer greater competitive advantage to the cell. One such function is its role in stimulating the synthesis of components of the translational machinery. For example, Fis stimulates transcription of rRNA and tRNA genes and genes for proteins involved in translation (19,35,40,51,56). Another role for Fis has been suggested in initiation of chromosomal DNA replication at oriC (12, 16). Cells carrying a fis null mutation show decreased stability of oriC minichromosomes (12, 16) and cannot reinitiate DNA re...