Lrp stimulates phase variation of type 1 fimbriation in Escherichia coli K-12

Abstract

The phase variation of type 1 fimbriation in Escherichia coli is associated with the inversion of a short DNA element. This element (switch) acts in cis to control transcription offimA, the major fimbrial subunit gene. Thus,fimA4 is transcribed when the switch is in one orientation (the on orientation) but not the other (the off orientation). Thefim inversion requires eitherfimB (on-to-off or off-to-on inversion) orfimE (on-to-offinversion only), as well as integration host factor, and is also influenced by the abundant DNA-binding protein H-NS. Here we report that an additional gene, lIrp, a factor known to influence the expression of both Pap and K99 fimbriae, is also required for normal activity of the fim switch. The frequencies of both fimB-promoted and fimE-promoted inversions, and consequently the phase variation of type 1 fimbriation, are lower in lIrp mutants. Lrp affects slightly the transcription of both fimB (which is increased) and fimE (which is decreased). We believe that these alterations in fimB and fimE transcription alone are unlikely to account for the sharp reduction in switching found in lrp mutants.Fimbriae, proteinaceous appendages produced by many gram-negative bacteria, promote adherence between bacterial and host cells. Although attachment is probably an important step in pathogenesis, fimbriae are also excellent immunogens (13,30,49,50), and their expression presumably leaves the cell vulnerable to the host's immune defenses. Perhaps to help avoid the immune system, the expression of many fimbrial types is phase variable. Thus, the ability to undergo phase variation, using a range of mechanisms (reviewed in reference 53) that involve changes in DNA methylation (8) and DNA inversion (1, 35), as well as other DNA rearrangements (24,38,60), may in itself be a pathogenicity factor (15).The phase variation of type 1 fimbriation in Escherichia coli involves inversion of a 314-bp DNA element (1). This element (switch), which is situated immediately upstream of fimA, acts in cis to control the transcription of fimA, the major fimbrial subunit gene (27,43

Global Gene Expression Profiling in Escherichia coliK12

“…The expression of this gene is controlled by a cis-acting DNA element (switch). Several reports have shown that switching frequency is reduced in IHF and lrp Ϫ strains (75,76). In agreement with these reports, our data show that fimA expression is reduced 4.3-fold in a lrp Ϫ strain.…”

A site-specific recombinase is required for competitive root colonization by Pseudomonas fluorescens WCS365

“…Three global regulators have been described to affect switching induced by fimB and fimE, namely IHF, the histone-like protein H-NS, and the leucine-responsive element (Lrp) (37,(42)(43)(44)(45)(46). Lrp differentially regulates switching in various media and is involved in the stimulation of switching upon addition of aliphatic amino acids (47).…”

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

“…We reported previously that rather than being slow and random, the fim switch is capable of high inversion frequencies (>0.7 per cell per generation) and is regulated by environmental conditions, including temperature and the amino acids alanine, leucine, isoleucine, and valine (11). In addition, lIrp is required for normal control of fim inversion and for amino acid stimulation offim (3,11). Here we show that Lrp binds in and adjacent to the fim switch and suggest that Lrp plays a direct role in fim recombination.…”

“…Lrp stimulation of the fim switch could be either direct with Lrp participating in fim recombination, or indirect, with Lrp regulating expression of a trans-acting factor. Both fimB transcription and fimE transcription are affected only slightly by mutation of lrp (3). Therefore, it is likely that the marked stimulation of fim by lrp is either direct or occurs through factors other than FimB and FimE. Lrp, a site-specific DNA-binding protein, controls a regulon of at least 40 genes in Escherichia coli, including fimbrial expression and amino acid transport, degradation, and biosyn-thesis (3,6,9,10,18,19,(22)(23)(24).…”

“…Both fimB transcription and fimE transcription are affected only slightly by mutation of lrp (3). Therefore, it is likely that the marked stimulation of fim by lrp is either direct or occurs through factors other than FimB and FimE. Lrp, a site-specific DNA-binding protein, controls a regulon of at least 40 genes in Escherichia coli, including fimbrial expression and amino acid transport, degradation, and biosyn-thesis (3,6,9,10,18,19,(22)(23)(24). The most extensive studies of Lrp have examined its role in the regulation of ilvIH transcription (19,22,23).…”