Regulation of fim genes in uropathogenic Escherichia coli

Abstract

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections in women, causing significant morbidity and mortality in this population. Adherence to host epithelial cells is a pivotal step in the pathogenesis of UPEC. One of the most important virulence factors involved in mediating this attachment is the type 1 pilus (type 1 fimbria) encoded by a set of fim genes arranged in an operon. The expression of type 1 pili is controlled by a phenomenon known as phase variation, which reversibly switches between the expression of type 1 pili (Phase-ON) and loss of expression (Phase-OFF). Phase-ON cells have the promoter for the fimA structural gene on an invertible DNA element called fimS, which lines up to allow transcription, whereas transcription of the structural gene is silenced in Phase-OFF cells. The orientation of the fimS invertible element is controlled by two site-specific recombinases, FimB and FimE. Environmental conditions cause transcriptional and post-transcriptional changes in UPEC cells that affect the level of regulatory proteins, which in turn play vital roles in modulating this phase switching ability. The role of fim gene regulation in UPEC pathogenesis will be discussed.

Keywords: Gene regulation; Type 1 fimbriae; Type 1 pili; Urinary tract; Uropathogenic Escherichia coli.

Figure 1. Schematic of the fim operon, including the characterized promoter sites

Figure 2. A schematic showing how the FimB and FimE proteins orient the fimS element

Figure 3. Schematic model of the actions of 20 auxiliary proteins on the regulation of type 1 pili

The inverted repeat left and right (IRL and IRR) are shown as open boxes. Binding sites for integration host factor (IHF I and II) and leucine-responsive protein (Lrp1, 2, and 3) are also represented as open boxes. Genes are displayed as black boxes and the promoters are shown as bent black arrows. The dark gray arrows correspond to FimB and the light gray arrows are for FimE. Black arrows signify an effect on the fimS element. Solid green arrows indicate confirmed binding associated with stimulatory effects, whereas dashed green arrows indicate presumed stimulatory effects. Solid red arrows indicate confirmed binding associated with repressing effects, whereas dashed red arrows indicate presumed repressing effects.