Role of FimW, FimY, and FimZ in regulating the expression of type i fimbriae in Salmonella enterica serovar Typhimurium.

Type I fimbriae in Salmonella enterica serovar Typhimurium are surface appendages that facilitate binding to eukaryotic cells. Expression of the fim gene cluster is known to be regulated by three proteins--FimW, FimY, and FimZ--and a tRNA encoded by fimU. In this work, we investigated how these proteins and tRNA coordinately regulate fim gene expression. Our results indicate that FimY and FimZ independently activate the P(fimA) promoter which controls the expression of the fim structural genes. FimY and FimZ were also found to strongly activate each other's expression and weakly activate their own expression. FimW was found to negatively regulate fim gene expression by repressing transcription from the P(fimY) promoter, independent of FimY or FimZ. Moreover, FimW and FimY interact within a negative feedback loop, as FimY was found to activate the P(fimW) promoter. In the case of fimU, the expression of this gene was not found to be regulated by FimW, FimY, or FimZ. We also explored the effect of fim gene expression on Salmonella pathogenicity island 1 (SPI1). Our results indicate that FimZ alone is able to enhance the expression of hilE, a known repressor of SPI1 gene expression. Based on our results, we were able to propose an integrated model for the fim gene circuit. As this model involves a combination of positive and negative feedback, we hypothesized that the response of this circuit may be bistable and thus a possible mechanism for phase variation. However, we found that the response was continuous and not bistable.