The nucleoid-associated protein Fis has an important role in the transcriptional control of Salmonella motility and virulence, according to a report from the research groups of Charles Dorman and Jay Hinton that has been published in the latest issue of Microbiology.

It has been known for many years that the effects of Fis, the factor for inversion stimulation — despite its name — are not restricted to DNA inversion. Results from many previous analyses have shown that this small DNA-binding and -bending protein not only influences DNA topology but also modulates the expression of a wide range of genes. In this latest work, Kelly et al. combined a microarray analysis with more specific assays to analyse the range of influence of Fis on gene expression in Salmonella enterica serovar Typhimurium.

In the microarray work, Fis-regulated genes were identified by comparing gene expression in a wild-type strain and a Fis-knockout mutant. This transcription profiling revealed that the most strongly Fis-activated genes were those located within the Salmonella chromosomal pathogenicity islands (SPI-1-5), particularly SPI-2, which encodes a type III secretion system (T3SS) required for survival within macrophages, and the motility and flagellar genes, also a T3SS. As the third Salmonella T3SS, which is required for invasion of epithelial cells, is located in SPI-1, these results show that Fis regulates all three TTSSs. More detailed analysis of the effects on representative flagellar and SPI-2 genes using transcription fusion and mobility shift assays showed that Fis affects these genes directly by binding to the promoter regions.

Among the most strongly Fis-repressed genes were genes involved in metabolism and transport, many of which are required for colonization of the gut. The authors propose the attractive hypothesis that the positive and negative regulatory effects of Fis — in concert with other regulators — allow the coordination of Salmonella motility and metabolism with virulence.

Previous work had indicated that Fis was involved in the regulation of virulence genes in Escherichia coli, Shigella flexneri and S. typhimurium. The analysis of Kelly et al. has given us a more detailed picture of the effects of Fis on S. typhimurium gene expression. Their results confirm that Fis is a global regulator with wide-ranging effects on gene expression, but have revealed that it acts mainly on specific gene sets.