Fim switch
The fim switch in Escherichia coli is the mechanism by which the fim gene cluster, encoding Type I Pili,{{Cite journal|title = Two regulatory fim genes, fimB and fimE, control the phase variation of type 1 fimbriae in Escherichia coli.|journal = The EMBO Journal|date = 1986|issn = 0261-4189|pmc = 1166953|pmid = 2874022|pages = 1389–1393|volume = 5|issue = 6|first = P|last = Klemm|doi = 10.1002/j.1460-2075.1986.tb04372.x}} is transcriptionally controlled.
These pili are virulence factors involved in adhesion, especially important in uropathogenic Escherichia coli. The gene undergoes phase variation mediated via two recombinases and is a model example of site specific inversion.
Structure and mechanism of phase variation
[[File:Phase variation site specific recombination - inversion.jpg|thumb|English: Phase and Antigenic Variation in Bacteria. pA is the promoter for FimA, pB is the
promoter for FimB and pE is the promoter for FimE. IRR is inverted
repeat right and IRL is inverted repeat left. FimB and FimE are
recombinases that can change the orientation of the FimA promoter by
inverting the IRR and IRL.]]
The operon consists of the promoter region fim S, the main constituent fim A, its gene product forming a rod like structure and fim H, coding for an adhesin at the tip, to name just a few important elements. The fim S region is flanked by 9bp repeats that are mirror images of each other.{{Cite journal|title = An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli|journal = Proceedings of the National Academy of Sciences|date = 1985|issn = 0027-8424|pmid = 2863818|pages = 5724–5727|volume = 82|issue = 17|first1 = J. M.|last1 = Abraham|first2 = C. S.|last2 = Freitag|first3 = J. R.|last3 = Clements|first4 = B. I.|last4 = Eisenstein|doi=10.1073/pnas.82.17.5724|pmc=390624|bibcode = 1985PNAS...82.5724A|doi-access = free}} These mirror images serve as substrates for two ATP-dependent recombinases, fim B and fim E. These recombinases can invert the orientation of the fim S region and only one orientation allows for 3' to 5' transcription.{{cn|date=December 2022}}
fim B "flips" the promoter region both ways, from the "on" position to the "off" position and vice versa, whereas fim E can only facilitate recombination from "on" to "off". This equilibrium, shifted towards maintaining the "off" position, due to higher fim E activity,{{Cite journal|title = Comparative analysis of FimB and FimE recombinase activity|journal = Microbiology|date = Dec 2007|issn = 1350-0872|pmid = 18048927|pages = 4138–4149|volume = 153|issue = Pt 12|doi = 10.1099/mic.0.2007/010363-0|first1 = Nicola|last1 = Holden|first2 = Ian C.|last2 = Blomfield|first3 = Bernt-Eric|last3 = Uhlin|first4 = Makrina|last4 = Totsika|first5 = Don Hemantha|last5 = Kulasekara|first6 = David L.|last6 = Gally|doi-access = free}} serves as a mode of expressing pili only when adhesion is needed. Another level of transcriptional control in E. coli is mediated by the sensitivity of the recombinases to pH and osmolarity,{{Cite journal|title = Osmolarity and pH Growth Conditions Regulate fim Gene Transcription and Type 1 Pilus Expression in Uropathogenic Escherichia coli|url= |journal = Infection and Immunity|date = 2002|issn = 0019-9567|pmid = 11854225|pages = 1391–1402|volume = 70|issue = 3|doi = 10.1128/IAI.70.3.1391-1402.2002|first1 = William R.|last1 = Schwan|first2 = Jeffrey L.|last2 = Lee|first3 = Farrah A.|last3 = Lenard|first4 = Brian T.|last4 = Matthews|first5 = Michael T.|last5 = Beck|pmc=127777}} further ensuring appropriate expression levels of type-I pili, given the stark differences in osmolarity inside and outside an animal's body. Type-I pili are expressed by many species of Enterobacteriaceae. The transcriptional control can differ widely between species,{{Cite journal|title = The Leucine-Responsive Regulatory Protein, Lrp, Activates Transcription of the fim Operon in Salmonella enterica Serovar Typhimurium via the fimZ Regulatory Gene|url= |journal = Journal of Bacteriology|date = 2008|issn = 0021-9193|pmid = 17981960|pages = 602–612|volume = 190|issue = 2|doi = 10.1128/JB.01388-07|first1 = Kirsty A.|last1 = McFarland|first2 = Sacha|last2 = Lucchini|first3 = Jay C. D.|last3 = Hinton|first4 = Charles J.|last4 = Dorman|pmc=2223685}} in Salmonella typhimurium, for example much influence is exerted by a leucine-responsive regulatory protein and there is no fim S element.