Archives of Microbiology

, Volume 163, Issue 5, pp 357–365 | Cite as

Escherichia coli and other species of the enterobacteriaceae encode a protein similar to the family of Mip-like FK506-binding proteins

  • Shelley M. Horne
  • Kevin D. YoungEmail author
Original Paper


A newly identified gene in Escherichia coli, fkpA, encodes a protein with extensive similarity to the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Chlamydia trachomatis. The FkpA protein may be a new member of the family of FK506-binding proteins (FKBPs) because its carboxyl domain includes a sequence that matches the consensus FK506-binding motif in 40 of 48 positions. including those amino acids at the active site that form hydrogen bonds with the drug FK506. The amino acid sequence of the 29kDa FkpA protein is 30–35% identical to the Mip proteins of L. pneumophila, L. micdadei, and C. trachomatis. Of the 270 amino acids of FkpA, 113 (42%) are identical to the sequence of one or another of these Mip proteins. Overexpression of FkpA or deletion of fkpA from the E. coli chromosome had no detrimental effect on bacterial growth, indicating that fkpA is not an essential gene. Hybridization of fkpA-specific DNA probes to genomic blots révealed that similar genes exist in several representatives of the Enterobacteriaceae. Thus, mip-like genes are not found exelusively in bacteria having a predominately intracellular life style, but instead appear to be a new FKBP subfamily that is a common constituent of many bacteria.

Key words

mip Gene Mip protein FK506-binding proteins FKBP Legionella pneumophila Escherichia 


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  1. Bangsborg JM, Cianciotto NP, Hindersson P (1991) Nucleotide sequence analysis of the Legionella micdadei mip gene, encoding a 30-kilodalton analog of the Legionella pneumophila Mip protein. Infect Immun 59:3836–3840PubMedGoogle Scholar
  2. Cianciotto NP, Fields BS (1992) Legionella pneumophila mip gene potentiates intracellular infection of protozoa and human macrophages. Proc Natl Acad Sci USA 89:5188–5191PubMedGoogle Scholar
  3. Cianciotto NP, Eisenstein BI, Mody CH, Toews GB, Engleberg NC (1989) A Legionella pneumophila gene encoding a species-specific surface protein potentiates initiation of intracellular infection. Infect Immun 57:1255–1262PubMedGoogle Scholar
  4. Cianciotto NP, Bangsborg JM, Eisenstein BI, Engleberg NC (1990a) Identification of mip-like genes in the genus Legionella. Infect Immun 58:2912–2918PubMedGoogle Scholar
  5. Cianciotto NP, Eisenstein BI, Mody CH, Engleberg NC (1990b) A mutation in the mip gene results in an attenuation of Legionella pneumophila virulence. J Infect Dis 162:121–126PubMedGoogle Scholar
  6. Clardy J (1993) Structural studies of complexed FK-506 binding protein. Ann N Y Acad Sci 685:37–45PubMedGoogle Scholar
  7. Consevage MW, Porter RD, Phillips AT (1985) Cloning and expression in Escherichia coli of histidine utilization genes from Pseudomonas putida. J Bacteriol 162:138–146PubMedGoogle Scholar
  8. Dreyfuss G, Adam SA, Choi YD (1984) Physical change in cytoplasmic messenger ribonucleoproteins in cells treated with inhibitors of mRNA transcription. Mol Cell Biol 4:415–423PubMedGoogle Scholar
  9. Dumais-Pope C, O'Connell W, Cianciotto NP (1993) Distribution and regulation of the Legionella mip gene. In: Barbaree JM, Breiman RF, Dufour AP (eds) Legionella: current status and emerging perspectives. American Society for Microbiology, Washington, DC, pp 70–72Google Scholar
  10. Engleberg NC, Pearlman E, Dixon D, Eisenstein BI (1986) Antibodies isolated by using cloned surface antigens recognize antigenically related components of Legionella pneumophila and other Legionella species. J Immunol 136:1415–1417PubMedGoogle Scholar
  11. Engleberg NC, Carter C, Weber DR, Cianciotto NP, Eisenstein BI (1989) DNA sequence of mip, a Legionella pneumophila gene associated with macrophage infectivity. Infect Immun 57:1263–1270PubMedGoogle Scholar
  12. Feinberg AP, Vogelstein B (1984) Addendum: a technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 137:266–267PubMedGoogle Scholar
  13. Fellay R, Frey J, Krisch H (1987) Interposon mutagenesis of soil and water bacteria: a family of DNA fragments designed for in vitro insertional mutagenesis of gram-negative bacteria. Gene 52:147–154CrossRefPubMedGoogle Scholar
  14. Finlay BB, Falkow S (1989) Common themes in microbial pathogenicity. Microbiol Rev 53:210–230PubMedGoogle Scholar
  15. Fischer G, Bang H, Ludwig B, Mann K, Hacker J (1992) Mip protein of Legionella pneumophila exhibits peptidyl-prolyl-cis/trans isomerase (PPIase) activity. Mol Microbiol 6:1375–1383PubMedGoogle Scholar
  16. Galat A (1993) Peptidylproline cis-trans-isomerases: immunophilins. Eur J Biochem 216:689–707PubMedGoogle Scholar
  17. Hacker J, Fischer G (1993) Immunophilins: structure-function relationship and possible role in microbial pathogenicity. Mol Microbiol 10:445–456PubMedGoogle Scholar
  18. Heitman J, Movva NR, Heistand PC, Hall MN (1991) FK506-binding protein proline rotamase is a target for the immunosuppressive agent FK506 in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 88:1948–1952PubMedGoogle Scholar
  19. Henikoff S (1984) Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene 28:351–359CrossRefPubMedGoogle Scholar
  20. Horne SM (1994) PhD Dissertation. University of North Dakota, Grand ForksGoogle Scholar
  21. Kino T, Goto T (1993) Discovery of FK-506 and update. Ann N Y Acad Sci 685:13–21PubMedGoogle Scholar
  22. Kohara Y, Akiyama K, Isono K (1987) The physical map of the whole E. coli chromosome: application of a new strategy for rapid analysis and sorting of a large genomic library. Cell 50:495–508CrossRefPubMedGoogle Scholar
  23. Kulakauskas S, Wikström PM, Berg DE (1991) Efficient introduction of cloned mutant alleles into the Escherichia coli chromosome. J Bacteriol 173:2633–2638PubMedGoogle Scholar
  24. Lundemose AG, Rouch DA, Birkelund S, Christiansen G, Pearce JH (1992) Chlamydia trachomatis Mip-like protein. Mol Microbiol 6:2539–2548PubMedGoogle Scholar
  25. Lundemose AG, Kay JE, Pearce JH (1993) Chlamydia trachomatis Mip-like protein has peptidyl-prolyl cis/trans isomerase activity that is inhibited by FK506 and rapamycin and is implicated in initiation of chlamydial infection. Mol Microbiol 7:777–783PubMedGoogle Scholar
  26. Maratea D, Young KD, Young R (1985) Deletion and fusion analysis of the phage X174 lysis gene E. Gene 40:39–46CrossRefPubMedGoogle Scholar
  27. Miller JH (1972) Experiments in molecular genetics. Cold Spring Harbor Laboratory, Cold Spring HarborGoogle Scholar
  28. Parsons WH, Sigal NH, Wyvratt MJ (1993) FK-506-a novel immunosuppressant. Ann N Y Acad Sci 685:22–36PubMedGoogle Scholar
  29. Roof WD, Horne SM, Young KD, Young R (1994) slyD, a host gene required for ϕX174 lysis, is related to the FKBP family of peptidyl-prolyl cis-trans isomerases. J Biol Chem 269:2902–2910PubMedGoogle Scholar
  30. Rudd KE (1992) Alignment of E. coli DNA sequences to a revised, integrated genomic restriction map. In: Miller JH (ed) A short course in bacterial genetics: a laboratory manual and handbook for Escherichia coli and related bacteria. Cold Spring Harbor Laboratory Press. Cold Spring Harbor, pp 2.3–2.43Google Scholar
  31. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Larbor Laboratory Press, Cold Spring HarborGoogle Scholar
  32. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467PubMedGoogle Scholar
  33. Schmid FX (1993) Prolyl isomerase: enzymatic catalysis of slow protein-folding reactions. Annu Rev Biophys Biomol Struct 22:123–143CrossRefPubMedGoogle Scholar
  34. Smith TF, Waterman MS (1981) Identification of common molecular subsequences. J Mol Biol 147:195–197PubMedGoogle Scholar
  35. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517PubMedGoogle Scholar
  36. Sturrock SS, Collins JF (1993) MPsrch version 1.3. Biocomputing Research Unit, University of Edinburgh, UKGoogle Scholar
  37. Trandinh CC, Pao GM, Saier MH Jr (1992) Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl-prolyl cis-trans isomerases. FASEB J 6:3410–3420PubMedGoogle Scholar
  38. Vieira J, Messing J (1987) Production of single-stranded plasmid DNA. Methods Enzymol 153:3–11CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  1. 1.Department of Microbiology and Immunology, School of MedicineUniversity of North DakotaGrand ForksUSA

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