Expression of type 1 fimbriae in Escherichia coli K-12 is phase variable and associated with the inversion of a short DNA element (switch). Thefim switch requires eitherfimB (on-to-off or off-to-on switching) orfimE (on-to-off switching only) and is affected by the global regulators leucine-responsive regulatory protein (Lrp), integration host factor (IHF), and H-NS. Here it is shown that switching frequencies are regulated by both temperature and media and that these effects appear to be independent. fimE-promoted on-to-off switching occurs far more rapidly than previously estimated (0.3 per cell per generation in defined rich medium at 37°C) and faster at lower than at higher temperatures. In direct contrast, fimB-promoted switching increases with temperature, with optima between 37 and 41°C. Switching promoted by both fimB andfimE is stimulated by aliphatic amino acids (alanine, isoleucine, leucine, and valine), and this stimulation requires lrp. Furthermore, lrp appears to differentially regulate fimB-andfimE-promoted switching in different media.Type 1 fimbriae are filamentous proteinaceous appendages produced by many species of enteric bacteria. Type 1 fimbriae promote attachment to a variety of eukaryotic cells by a process inhibited by mannose (24). Recent evidence suggests that type 1 fimbriae play an important role in communicability (3). The expression of type 1 fimbriae may play a role in urinary tract infections (24). However, type 1 fimbriae are excellent immunogens (10,28,39,40). Thus, the capacity to switch rapidly their expression off or on, particularly in response to specific signals, should be advantageous to the organism and consequently important in pathogenesis.Type 1 fimbrial phase variation is associated with the inversion of a 314-bp DNA element (1). This switch (invertible element) contains a promoter forfimA, the main fimbrial structural subunit gene (16). Thus, fimA is expressed in one orientation (on) but not the other (off). Switching is RecA independent (site specific) and requires eitherfimB (on-to-off or off-to-on switching) or fimE (on-to-off switching only) (6,17,27,32,33,38). In addition to fimB and fimE, genes situated adjacent to the switch, switching is also influenced by at least three global regulators, leucine-responsive regulatory protein (Lrp), H-NS, and integration host factor (IHF) (4,11,15,21,26,45). Recently, we and others have shown that many K-12 strains studied are fimE mutants and that slow switching results from these mutations (6). Preliminary analysis of fimE+ K-12 strains demonstrated that on-to-off switching is much faster (at least 0.01 per cell per generation) than fimB-promoted switching (10-3 to 10-) (4, 6). Mutations in lrp (Lrp) and himA and himD (IHF) markedly reduce both fimB-and fimE-promoted switching (4,11,15 background (21,26,45). Interestingly, others have noted heterogeneity in control of phase variation among clinical isolates (2,18,22,23,41,42) presumably reflecting differences in the genetic compositions of these strains.The fim switch in...