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The integration site of the iga gene in commensal Neisseria sp.

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An IgA1 protease is produced by the human pathogens Neisseria gonorrhoeae and N. meningitidis but not by related non-pathogenic, commensal, Neisseria species. In this study, the chromosomal iga locus was characterized in the N. gonorrhoeae strain MS11 and compared to corresponding loci in N. meningitidis and commensal Neisseria species. In N. gonorrhoeae, the genes trpB and ksgA were found immediately downstream of iga. In addition to comL and comA, a homolog of the Escherichia coli YFII gene was identified upstream of iga. Each gene in the iga region (YFII and comL, comA and iga, and trpB and ksgA) is transcribed in the opposite direction to its neighbors. The comL/comA and iga/trpB pairs each have a transcriptional terminator in the correct position for joint use. These terminators contain the common gonococcal DNA uptake sequence (DUS). A highly conserved direct repeat of 25 bp located immediately adjacent to the iga gene in N. gonorrhoeae was also found in N. meningitidis. In Southern hybridization experiments, no homology to iga was detectable in the chromosomal DNAs of the commensal species N. mucosa, N. lactamica, N. flavescens, N. cinerea, N. subflava, N. flava, N. sicca or N. elongata. When N. gonorrhoeae comL and trpB were used as probes, signals were detected on the same restriction fragment in six of the eight species. This indicated that commensal Neisseria species share a possible integration site for the iga gene between comA and trpB. The region between comA and trpB was therefore amplified by PCR. The fragment obtained from N. lactamica showed a high degree of homology to gonococcal comA and trpB, respectively, but iga was replaced by a sequence of 13 bp that shows no homology to any known gonococcal sequence. Our data suggest that iga was acquired by a common ancestor of N. gonorrhoeae and N. meningitidis rather than being distributed by horizontal gene transfer. N. lactamica, which is more closely related to N. gonorrhoeae than other commensals, may have lost iga by deletion.

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  1. Aho EL, Murphy GL, Cannon, JG (1987) Distribution of specific DNA sequences among pathogenic and commensal Neisseria species. Infect Immun 55:1009–1013

  2. Blum G, Ott M, Lischewski A, Ritter A, Immrich, H, Tschäppe H, Hacker J (1994) Excission of large DNA regions termed pathogenicity islands from tRNA-specific loci in the chromosome of an Escherichia coli wild-type pathogen. Infect Immun 62:606–614

  3. Boyer HW, Roulland-Dussoix D (1969) A complementation analysis of the restriction and modification of DNA in Escherichia coli. J Mol Biol 41:248–254

  4. Crawford IP, Eberly L (1989) DNA sequence of the tryptophan synthase genes of Pseudomonas putida. Biochimie 71:521–531

  5. Devereux J, Haeberli P, Smithies O (1984) A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 12:387–395

  6. Elkins C, Thomas CE, Seifert HS, Sparling PF (1991) Species-specific uptake of DNA by gonococci is mediated by a 10-base-pair sequence. J Bacteriol 173:3911–3913

  7. Facius D, Meyer TF (1993) A novel determinant (comA) essential for natural transformation competence in Neisseria gonorrhoeae and the effect of a comA defect on pilin variation. Mol Microbiol 10:699–712

  8. Facius D, Fussenegger M, Meyer TF (1996) Sequential action of factors involved in natural competence for transformation of Neisseria gonorrhoeae. FEMS Microbiol Lett 137:159–164

  9. Fermer C, Kristiansen BE, Skold O, Swedber G (1995) Sulfonamide resistance in Neisseria meningitidis as difined by site directed mutagenesis could have its origin in other species. J Bacteriol 177:4667–4675

  10. Fleischmann, RD Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, et al (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269:496–512

  11. Fussenegger M, Facius D, Meier J, Meyer TF (1996a) A novel peptidoglycan-linked lipoprotein (ComL) that functions in natural transformation competence of Neisseria gonorrhoeae. Mol Microbiol 19:1095–1105

  12. Fussenegger M, Rudel T, Barten R, Ryll R, Meyer TF (1996b) Transformation competence and type 4 pilus biogenesis in Neisseria gonorrhoeae. Gene 192:125–134

  13. Gibbs CP, Meyer TF (1996) Genome plasticity in Neisseria gonorrhoeae. FEMS Microbiol Lett 145:173–179

  14. Gibbs CP, Reimann BY, Schulz E, Kaufmann A, Haas R, Meyer TF (1989) Reassorment of pilin genes in Neisseria gonorrhoeae occurs by two distinct mechanisms. Nature 338:651–652

  15. Halter R, Pohlner J, Meyer TF (1984) IgA protease of Neisseria gonorrhoeae: isolation and characterization of the gene and its extracellular product. EMBO J 3:1595–1601

  16. Halter R, Pohlner J, Meyer TF (1989) Mosaic-like organization of IgA protease genes in Neisseria gonorrhoeae generated by horizontal genetic exchange in vivo. EMBO J 8:2737–2744

  17. Hyde CC, Ahmed SA, Padlan EA, Miles EW, Davies DR (1988) Three-dimensional structure of the tryptophane synthase α2β2 multienzyme complex from Salmonella typhimurium. J Biol Chem 263:17857–17871

  18. Jose J, Wölk U, Lorenzen D, Wenschuh H, Meyer TF (2000) Human T cell response to meningococcal IgA 1 protease associated α-proteins. Scand J Immunol, 51:176–184

  19. Klauser T, Krämer J, Otzelberger K, Pohlner J, Meyer T (1993) Characterization of the Neisseria Igaβ-core. The essential unit for outer membrane targeting and extracellular protein secretion. J Mol Biol 234:579–593

  20. Kroll JS, Wilks KE, Farrant JL, Langford PR (1998) Natural genetic exchange between Haemophilus and Neisseria —intergenic transfer of chromosomal genes between major human pathogens. Proc Natl Acad Sci 95:12381–12385

  21. Lawson FS, Billowes FM, Dillon JAR (1995) Organization of carbamoyl-phosphate synthetase genes in Neisseria gonorrhoeae includes a large, variable intergenic sequence which is also present in other Neisseria species. Microbiology 141:1183–1191

  22. Leying H, Suerbaum S, Geis G, Haas R (1992) Characterisation of flaA, a Helicobacter pylori flagellin gene. Mol Microbiol 6:2863–2874

  23. Lomholt H (1996) Molecular biology and vaccine aspects of bacterial immunglobulin A1 proteases. APMIS Suppl 62:5–28

  24. Lomholt H, Poulsen K, Kilian M (1995) Comparative characterization of the iga gene encoding IgA1 protease in Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae. Mol Microbiol 15:495–506

  25. Maiden MCJ, Malorny B, Achtman M (1996) A global gene pool in the Neisseria. Mol Microbiol 21:1297–1298

  26. Meyer TF, Pohlner J, van Putten JPM (1994) Biology of the pathogenic Neisseriae. In: Dangl, J.L. (ed.) Bacterial pathogenesis of plants and animals. Curr Topics Microbiol Immunol 192:283–317

  27. O'Rourke M, Stevens E (1993) Genetic structure of Neisseria gonorrhoeae populations: a non-clonal pathogen. J Gen Microbiol 139:2603–2611

  28. Parkhill J, Achtman M, James KD, Bentley SD, Churcher C, Klee SR, Morelli G, Basham D, Brown D, Chillingworth T, Davies RM, Davis P, Devlin K, Feltwell T, Hamlin N, Holroyd S, Jagels K, Leather S, Moule S, Mungall K, Quail M.A., Rajandream MA, Rutherford K.M., Simmonds M, Skelton J, Whitehead S, Spratt BG, Barrell BG (2000) Complete DNA sequence of a serogroup A strain of Neisseria menigitidis Z2491. Nature 404:502–506

  29. Pohlner J, Halter R, Beyreuther K, Meyer TF (1987) Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease. Nature 325:458–462

  30. Robertson BDR, Frosch M, van Putten JPM (1993) The role of galE in the biosynthesis and function of gonococcal lipopolysaccharide. Mol Microbiol 8:891–901

  31. Römling U, Greipel J, Tümmler B (1995) Gradient of genomic diversity in the Pseudomonas aeruginosa chromosome. Mol Microbiol 17:323–332

  32. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York

  33. Sparling PF (1966) Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. J Bacteriol 92:1364–1369

  34. Spratt BG, Bowler LD, Zhang QY, Zhou J, Maynard Smith J (1992) Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species. J Mol Evol 34:115–125

  35. Stern A, Nickel P, Meyer TF, So M (1984) Opacity determinants of Neisseria gonorrhoeae: Gene expression and chromosomal linkage to the gonococcal pilus gene. Cell 37:447–456

  36. Van Buul CP, van Knippenberg PH (1985) Nucleotide sequence of the ksgA gene of Escherichia coli: comparison of methyltransferases effecting dimethylation of adenosine in ribosomal RNA. Gene 38:65–72

  37. Vázques J, Berrón S, O`Rourke M, Carpenter G, Feil E, Smith NH, Spratt BG (1995) Interspecies recombination in nature: a meningococcus that has acquired a gonococcal PIB porin. Mol Microbiol 15:1001–1007

  38. Vedros NA (1984) Neisseria. In: Krieg NR, Holt JG (eds) Bergey's manual of systematic bacteriology, vol 1. Williams & Wilkins, Baltimore, pp 290–296

  39. Wolff K, Stern A (1995) Identification and characterization of specific sequences encoding pathogenicity associated proteins in the genome of commensal Neisseria species. FEMS Microbiol Lett 125:255–264

  40. Zhou J, Bowler LD, Spratt BG (1997) Interspecies recombination, and phylogenetic distortions, within the glutamine synthetase and shikimate dehydrogenase genes of Neisseria meningitidis and commensal Neisseria species. Mol Microbiol 23:799–812

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The authors wish to thank Dr. M. Dittrich and M. Goller for critical reading of the manuscript and C. Lanz for DNA sequencing, as well as B. Pichler-Brand for oligonucleotide synthesis. This work was supported by the BMBF competence network "genomic research on pathogenic bacteria (Pathogenomik)".

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Correspondence to T. F. Meyer.

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Communicated by W. Goebel

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Jose, J., Otto, G.W. & Meyer, T.F. The integration site of the iga gene in commensal Neisseria sp.. Mol Gen Genomics 269, 197–204 (2003). https://doi.org/10.1007/s00438-002-0799-6

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  • IgA protease
  • Gene organization
  • Recombination
  • Neisseria gonorrhoeae
  • Commensals