Role of FimW, FimY, and FimZ in Regulating the Expression of Type I Fimbriae in Salmonella enterica Serovar Typhimurium

Abstract

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.

Flagellated but Not Hyperfimbriated Salmonella enterica Serovar Typhimurium Attaches to and Forms Biofilms on Cholesterol-Coated Surfaces

“…The colonies with transposon insertions in fimW that were recovered in the cholesterol-binding screen were more numerous than the colonies with transposon insertions in any other gene that were recovered. FimW negatively regulates production of type 1 fimbriae by interacting with FimY (83) and possibly with FimZ (96); the latter two proteins independently activate the P fimA promoter, which controls the expression of the fim structural genes (83). Serovar Typhimurium chromosomal fimW mutants expressed 4-to 8-fold more type 1 fimbriae than the parent strain (96).…”

More than One Way To Control Hair Growth: Regulatory Mechanisms in Enterobacteria That Affect Fimbriae Assembled by the Chaperone/Usher Pathway

“…For example, the fimbrial regulatory proteins MrpJ, FimZ, and SfaX, originally described as affecting fimbria production in Proteus mirabilis, S. Typhimurium, and pathogenic E. coli, respectively, have also been implicated in controlling flagellum production at the level of gene expression (24,55,78). Besides both fimbria and flagellum gene expression, FimZ has also been shown to control invasion gene expression by acting at the level of another regulator, HilE (75).…”

“…Specifically, FimZ and FimY are able to induce each other's expression (75). FimY is also able to induce expression of fimW, which results in repression of P fimY promoter activity.…”

“…FimY is also able to induce expression of fimW, which results in repression of P fimY promoter activity. Rao and colleagues (75) suggested that type 1 fimbrial expression is controlled by a positive feedback loop involving FimY and FimZ as well as a negative feedback loop between FimW and FimY. In addition, the expression of fimZ itself has been shown to be controlled at the level of transcription by Lrp, and Lrp-negative mutants show no fim expression (59).…”

“…Typhimurium type 1 fimbriae, produced by the fim operon, are mannose-sensitive hemagglutinins that decorate the surface of the cell. The regulatory genes fimW, fimY, and fimZ encode proteins that affect the expression of the major subunit gene fimA (75,81,82,94). Additionally, upstream of fimW is fimU, which encodes a tRNA that is required for adequate expression of the regulatory proteins (79).…”