The leucine-responsive regulatory protein binds to the fim switch to control phase variation of type 1 fimbrial expression in Escherichia coli K-12.

Phase variation of type 1 fimbriation in Escherichia coli is associated with the site-specific recombination of a 314-bp DNA invertible element. The fim switch directs transcription of fimA, the major fimbrial subunit gene, in one orientation (on) but not the other (off). Switching requires either fimB (on-to-off or off-to-on inversion) or fimE (on-to-off inversion only) and is reduced sharply in strains containing lrp::Tn10 mutations. Both fimE-promoted switching and fimB-promoted switching are stimulated by the amino acids alanine, isoleucine, leucine, and valine, and this regulation requires lrp. Here it is shown that the leucine-responsive regulatory protein (Lrp) binds in and adjacent to the fim switch. Mutations in fim that lower Lrp binding in vitro have corresponding effects on both fimB-promoted switching and fimE-promoted switching in vivo. Lrp initiates binding at one of two sites within the fim switch. Additional cooperative binding results in an extensive region of protection from both DNase I and 1,10-phenanthroline-copper complex-activated DNA cleavage. The region of protection can extend to within 12 bp of the right inverted repeat (switch off) and occupies over one-third of the switch. It is proposed that wrapping of fim DNA around an Lrp complex is required to form a recombination-proficient structure.