Antonie van Leeuwenhoek

, Volume 76, Issue 1–4, pp 367–376 | Cite as

Anchoring of proteins to lactic acid bacteria

Article

Abstract

The anchoring of proteins to the cell surface of lactic acid bacteria (LAB) using genetic techniques is an exciting and emerging research area that holds great promise for a wide variety of biotechnological applications. This paper reviews five different types of anchoring domains that have been explored for their efficiency in attaching hybrid proteins to the cell membrane or cell wall of LAB. The most exploited anchoring regions are those with the LPXTG box that bind the proteins in a covalent way to the cell wall. In recent years, two new modes of cell wall protein anchoring have been studied and these may provide new approaches in surface display. The important progress that is being made with cell surface display of chimaeric proteins in the areas of vaccine development and enzyme- or whole-cell immobilisation is highlighted.

Lactococcus lactis Lactobacillus subsp. Staphylococcus carnosus Staphylococcus xylosus Streptococcus gordonii surface display 

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References

  1. Andréoni C, Goetsch L, Libon C, Samuelson P, Nguyen TN, Robert A, Uhlén M, Binz H & Ståhl S (1997) Flow cytometric quantification of surface-displayed recombinant receptors on staphylococci. BioTechniques 23: 696-704Google Scholar
  2. Boot HJ, Kolen CPAM, Van Noort JM & Pouwels PH (1993) S-layer protein of Lactobacillus acidophilus ATCC 4356: purification, expression in Escherichia coli, and nucleotide sequence of the corresponding gene. J. Bacteriol. 175: 6089-6096Google Scholar
  3. Buist G (1997) AcmA of Lactococcus lactis, a cell-binding major autolysin. Ph.D. thesis, University of Groningen, Haren, The NetherlandsGoogle Scholar
  4. Buist G, Kok J, Leenhouts KJ, Dabrowska M, Venema G & Haandrikman AJ (1995) Molecular cloning and nucleotide sequence of the gene encoding the major peptidoglycan hydrolase of Lactococcus lactis, a muramidase needed for cell separation. J. Bacteriol. 177: 1554-1563Google Scholar
  5. Callegari ML, Riboli B, Sanders JW, Cocconcelli PS, Kok J, Venema G & Morelli L (1998) The S-layer gene of Lactobacillus helveticus CNRZ 892: cloning, sequence and heterologous expression. Microbiol. 144: 719-726Google Scholar
  6. Di Fabio S, Medaglini D, Rush CM, Corrias F, Panzini GL, Pace M, Verani P, Pozzi G & Titti F (1998) Vaginal immunization of Cynomolgus monkeys with Streptococcus gordonii expressing HIV-1 and HPV16 antigens. Vaccine 16: 485-492Google Scholar
  7. Eko FO, Witte A, Huter V, Kuen B, Fürst-Ladani S, Haslberger A., Katinger A, Hensel A, Szostak MP, Resch S. Mader S. Raza P, Brand E, Marchart J, Jechlinger W, Haidinger W & Lubitz W (1999) New strategies for combination vaccines based on the extended recombinant bacterial ghost system. Vaccine 17: 1643-1649Google Scholar
  8. Fischetti VA, Medaglini D & Pozzi G (1996) Gram-positive commensal bacteria for mucosal vaccine delivery. Curr. Opin. Biotechnol. 7: 659-666Google Scholar
  9. Fischetti VA, Medaglini D, Oggioni M & Pozzi G (1993) Expression of foreign proteins on Gram-positive commensal bacteria for mucosal vaccine delivery. Curr. Opin. Biotechnol. 4: 603-610Google Scholar
  10. Fischetti VA, Pancholi V & Schneewind O (1990) Conservation of a hexapeptide sequence in the anchor region of surface proteins from Gram-positive cocci. Mol. Microbiol. 4: 1603-1605Google Scholar
  11. Franke CM (1998) Topology of a type I secretion system for bacteriocins of Lactococcus lactis. Ph.D. thesis, University of Groningen, Haren, The NetherlandsGoogle Scholar
  12. Franke CM, Leenhouts KJ, Haandrikman AJ, Kok J, Venema G & Venema K (1996) Topology of LcnD, a protein implicated in the transport of bacteriocins from Lactococcus lactis. J. Bacteriol. 178: 1766-1769Google Scholar
  13. Georgiou G, Stathopoulos C, Daugherty PS, Nayak AR, Iverson BL & Curtiss III R (1997) Display of heterologous proteins on the surface of microorganisms: from the screening of combinatorial libraries to live recombinant vaccines. Nature Biotechnol. 15: 29-34Google Scholar
  14. Gunneriusson E, Samuelson P, Uhlén M, Nygren PA & Ståhl S (1996) Surface display of a functional single chain Fv antibody on staphylococci. J. Bacteriol. 178: 1341-1346Google Scholar
  15. Haandrikman AJ, Kok J & Venema G (1991) Lactococcal proteinase maturation protein PrtM is a lipoprotein. J. Bacteriol. 173: 4517-4525Google Scholar
  16. Hansson M, Ståhl S, Nguyen TN, Bächi T, Robert A, Binz H, Sjölander A & Uhlén M (1992) Expression of recombinant proteins on the surface of the coagulase-negative bacterium Staphylococcus xylosus. J. Bacteriol. 174: 4239-4245Google Scholar
  17. Hofnung M (1991) Expression of foreign polypeptides at the Escherichia coli cell surface. Methods Cell Biol. 34: 77-105Google Scholar
  18. Holck A & Næs H (1992) Cloning, sequencing and expression of the gene encoding the cell-envelope-associated proteinase from Lactobacillus paracasei subsp. Paracasei NCDO151. J. Gen. Microbiol. 138: 1353-1364Google Scholar
  19. Kok J, Leenhouts KJ, Haandrikman AJ, Ledeboer AM & Venema G (1988) Nucleotide sequence of the cell wall-associated proteinase gene of Streptococcus cremoris Wg2. Appl. Environ. Microbiol. 54: 231-238Google Scholar
  20. Leer RJ, Antonissen C, Bergmans A, Jore J, Boersma WJA & Pouwels PH (1996) A new series of Lactobacillus expression vectors. Abstracts of the Fifth Symposium of Lactic Acid Bacteria: Genetics, Metabolism and Applications. Veldhoven, The Netherlands, Abstract no. E8Google Scholar
  21. Liljeqvist S, Samuelsen P, Hansson M, Nguyen TN, Binz H & Ståhl S (1997) Surface display of the cholera toxin subunit on Staphylococcus xylosus and Staphylococcus carnosus. Appl. Environ. Microbiol. 63: 2481-2488Google Scholar
  22. Maassen CBM, Laman JD, Heijne Den Bak-Glashouwer MJ, Tielen FJ, Van Holten-Neelen JCPA, Hoogteijling L, Antonissen C, Leer RJ, Pouwels PH, Boersma WJA & Shaw DM (1999) Instruments for oral disease-intervention strategies: recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis. Vaccine 17: 2117-2128Google Scholar
  23. Medaglini D, Oggioni MR & Pozzi G (1998) Vaginal immunization with recombinant gram-positive bacteria. Am. J. Repr. Immunol. 39: 199-208Google Scholar
  24. Medaglini D, Pozzi G, King TP & Fischetti VA (1995) Mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium Streptococcus gordonii after oral colonization. Proc. Natl. Acad. Sci. USA 92: 6868-6872Google Scholar
  25. Medaglini D, Rush CM, Sestini P & Pozzi G (1997) Commensal bacteria as vectors for mucosal vaccines against sexually transmitted diseases: vaginal colonization with recombinant streptococci induces local and systemic antibodies in mice. Vaccine 15: 1330-1337Google Scholar
  26. Mercenier A, Dutot P, Kleinpeter P, Aguirre M, Paris P, Reymund J & Slos P (1996) Development of lactic acid bacteria as live vectors for oral or local vaccines. Adv. Food Sci. 18: 73-77Google Scholar
  27. Navarre WW & Schneewind O (1994) Proteolytic cleavage and cell wall anchoring at the LPXTG motif of surface proteins in Gram-positive bacteria. Mol. Microbiol. 14: 115-121Google Scholar
  28. Navarre WW & Schneewind O (1999) Surface proteins of Gram-positive bacteria and mechanisms of their targeting to the cell wall envelope. Microbiol. Mol. Biol. Rev. 63: 174-229Google Scholar
  29. Navarre WW, Ton-That H, Faull KF & Schneewind O (1998) Anchor structure of staphylococcal surface proteins. II. COOH-terminal structure of muramidase and amidase-solubilized surface protein. J. Biol. Chem. 273: 29135-29142Google Scholar
  30. Nguyen TN, Gourdon MH, Hansson M, Robert A, Samuelson P, Libon C, Andréoni C, Nygren PA, Binz H, Uhlén M, & Ståhl S (1995) Hydrophobicity engineering to facilitate surface display of heterologous gene products on Staphylococcus xylosus. J. Biotechnol. 42: 207-219Google Scholar
  31. Nguyen TN, Hansson M, Ståhl S, Bächi T, Robert A, Domzig W, Binz H & Uhlén M (1993) Cell-surface display of heterologous epitopes on Staphylococcus xylosus as a potential delivery system for oral vaccination. Gene 128: 89-94Google Scholar
  32. Norton PM, Brown HWG, Wells JM, Macpherson AM, Wilson PW & Le Page RWF (1996) Factors affecting the immunogenicity of tetanus toxin fragment C expressed in Lactococcus lactis. FEMS Immunol. Med. Microbiol. 14: 167-177Google Scholar
  33. Norton PM, Le Page RWF & Wells JM (1995) Progress in the development of Lactococcus lactis as a recombinant mucosal vaccine delivery system. Folia Microbiol. 40: 225-230Google Scholar
  34. Oggioni MR & Pozzi G (1996) A host-vector system for heterologous gene expression in Streptococcus gordonii. Gene 169: 85-90Google Scholar
  35. Oggioni MR, Manganelli R, Contorni M, Tommasimo M & Pozzi G (1995) Immunization of mice by oral colonization with live recombinant commensal streptococci. Vaccine 13: 775-779Google Scholar
  36. Piard JC, Hautefort I, Fischetti VA, Ehrlich SD, Fons M & Grass A (1997a) Cell wall anchoring of the Streptococcus pyogenes M6 protein in various lactic acid bacteria. J. Bacteriol. 179: 3068-3072Google Scholar
  37. Piard JC, Jimenez-Diaz R, Fischetti VA, Ehrlich SD & Grass A (1997b) The M6 protein of Streptococcus pyogenes and its potential as a tool to anchor biologically active molecules at the surface of lactic acid bacteria. In: Horaud et al. (Eds) Streptococci and the Host, (pp. 545-550). Plenum Press, New York, USAGoogle Scholar
  38. Poquet I, Ehrlich SD & Grass A (1998) An export-specific reporter designed for gram-positive bacteria: application to Lactococcus lactis. J. Bacteriol. 180: 1904-1912Google Scholar
  39. Pouwels PH, Leer RJ & Boersma WJA (1996) The potential of Lactobacillus as a carrier for oral immunization: Development and preliminary characterization of vector systems for targeted delivery of antigens. J. Biotechnol. 44: 183-192Google Scholar
  40. Pouwels PH, Leer RJ, Shaw M, Heijne den Bak-Glashouwer MJ, Tielen FD, Smit E, Martinez B, Jore J & Conway PL (1998) Lactic acid bacteria as antigen delivery vehicles for oral immunization purposes. Int. J. Food Microbiol. 41: 155-167Google Scholar
  41. Pozzi G & Wells JM (1997a) Gram-Positive Bacteria. Vaccine Vehicles for Mucosal Immunization. Landes Biosciences Georgetown, TX, USAGoogle Scholar
  42. Pozzi G, Contorni M, Oggioni MR, Manganelli R, Tommasino M, Cavalieri F & Fischetti VA (1992a) Delivery and expression of a heterologous antigen on the surface of streptococci. Infect. Immun. 60: 1902-1907Google Scholar
  43. Pozzi G, Oggioni MR & Medaglini D (1997b) Recombinant Streptococcus gordonii as live vehicle for vaccine antigens. In: Pozzi G & Wells JM (Eds) Gram-positives Bacteria. Vaccine Vehicles for Mucosal Immunization (pp. 35-60). Landes Bioscience Georgetown, TX, USAGoogle Scholar
  44. Pozzi G, Oggioni MR, Manganelli R & Fischetti VA (1992b) Expression of M6 protein gene of Streptococcus pyogenes in Streptococcus gordonii after chromosomal integration and transcription. Res. Microbiol. 143: 449-457Google Scholar
  45. Pozzi G, Oggioni MR, Manganelli R, Medaglini D, Fischetti VA, Fenoglio D, Valle MT, Kunkl A & Manca F (1994) Human T-helper cell recognition of an immunodominant epitope of HIV-1 gp120 expressed on the surface of Streptococcus gordonii. Vaccine 12: 1071-1077Google Scholar
  46. Pugsley AP (1993) The complete general secretory pathway in Gram-negative bacteria. Microbiol. Rev. 57: 50-108Google Scholar
  47. Ricci S, Rush CM, Medaglini D & Pozzi G (1996) Expression of the Escherichia coli heat labile toxin subunit B in Streptococcus gordonii. Abstr. XII European Meeting on Bacterial Gene Transfer and Expression. Siena, Italy, p. 88Google Scholar
  48. Robert A, Samuelson P, Andréoni C, Bächi T, Uhlén M, Binz H, Nguyen TN & Ståhl S (1996) Surface display on staphylococci: a comparative study. FEES Lett. 390: 327-333Google Scholar
  49. Robinson K, Chamberlain LM, Schofield KM, Wells JM & Le Page RWF (1997) Oral vaccination of mice against tetanus with recombinant Lactococcus lactis. Nature Biotechnol. 15: 653-657Google Scholar
  50. Rush CM, Mercenier A & Pozzi G (1997) Expression of vaccine antigens in Lactobacillus. In: Pozzi G & Wells JM (Eds) Gram-positive Bacteria. Vaccine Vehicles for Mucosal Immunization (pp. 107-144). Landes Bioscience Georgetown, TX, USAGoogle Scholar
  51. Samuelson P, Hansson M, Ahlborg N, Andréoni C, Götz F, Bächi T, Nguyen TN, Binz H, Uhlén M & Ståhl S (1995) Cell surface display of recombinant proteins on Staphylococcus carnosus. J. Bacteriol. 177: 1470-1476Google Scholar
  52. Schneewind O, Fowler A & Faull KF (1995) Structure of the cell wall anchor of surface proteins in Staphylococcus aureus. Science 268: 103-106Google Scholar
  53. Schneewind O, Mihaylova-Petkov D & Model P (1993) Cell wall sorting signals in surface proteins of Gram-positive bacteria. EMBO J. 12: 4803-4811Google Scholar
  54. Schneewind O, Model P & Fischetti VA (1992) Sorting of protein A to the staphylococcal cell wall. Cell 70: 267-281Google Scholar
  55. Sleytr UB, Bayley H, Sára M, Breitwieser A, Küpcü S, Mader C, Weigert S, Unger FM & et al. (1997) Applications of S-layers. FEMS Microbiol. Rev. 20: 151-175Google Scholar
  56. Sousa C, Cebolla A & De Lorenzo V (1996) Enhanced metalloadsorption of bacterial cells displaying poly-His peptides. Nature Biotechnol. 14: 1017-1020Google Scholar
  57. Ståhl S & Uhlén M (1997a) Bacterial surface display: trends and progress. Trends Biotechnol. 15: 185-192Google Scholar
  58. Ståhl S, Samuelson P, Hansson M, Andréoni C, Goetsch L, Libon C, Liljeqvist S, Gunneriusson E, Binz H, Nguyen TN & Uhlén M (1997b) Development of non-pathogenic staphylococci as vaccine delivery vehicles. In: Pozzi G & Wells JM (Eds) Gram-positive Bacteria. Vaccine Vehicles for Mucosal Immunization (pp. 61-81). Landes Bioscience Georgetown, TX, USAGoogle Scholar
  59. Steidler L, Viaene J, Fiers W & Remaut E (1998) Functional display of a heterologous protein on the surface of Lactococcus lactis by means of the cell wall anchor of Staphylococcus aureus protein A. Appl. Environ. Microbiol. 64: 342-345Google Scholar
  60. Strauss A & Götz F (1996) In vivo immobilization of enzymatically active polypeptides on the cell surface of Staphylococcus carnosus. Mol. Microbiol. 21: 491-500Google Scholar
  61. Strauss A, Thumm G & Götz F (1998) Influence of Lif, the lysostaphin immunity factor, on acceptors of surface proteins and cell wall sorting efficiency in Staphylococcus carnosus. J. Bacteriol. 180: 4960-4962Google Scholar
  62. Toba T, Virkola R, Westerlund B, Björkman Y, Sillanpää J, Vartio T, Kalkkinen N & Korhonen TK (1995) A collagen-binding S-layer protein in Lactobacillus crispatus. Appl. Environ. Microbiol. 61: 2467-2471Google Scholar
  63. Ton-That H, Faull KF & Schneewind O (1997) Anchor structure of staphylococcal surface proteins. A branched peptide that links the carboxyl terminus of proteins to the cell wall. J. Biol. Chem. 272: 22285-22292Google Scholar
  64. Ton-That H, Labischinski H, Berger-Bächi & Schneewind O (1998) Anchor structure of staphylococcal surface proteins. III. Role of the FemA, FemB, and FemX factors in anchoring surface proteins on the bacterial cell wall. J. Biol. Chem. 273: 29143-29149Google Scholar
  65. Tynkkynen S, Buist G, Kunji E, Kok J, Poolman B, Venema G & Haandrikman AJ (1993) Genetic and biochemical characterization of the oligopeptide transport system of Lactococcus lactis. J. Bacteriol. 175: 7523-7532Google Scholar
  66. Vidgrén G, Palva I, Pakkanen R, Lounatmaa K & Palva A (1992) S-layer protein gene of Lactobacillus brevis: cloning by polymerase chain reaction and determination of the nucleotide sequence. J. Bacteriol. 174: 7419-7427Google Scholar
  67. Vos P, Simons G, Siezen RJ & De Vos WM (1989) Primary structure and organization of the gene for a prokaryotic cell envelope-located serine proteinase. J. Biol. Chem. 264: 13579-13585Google Scholar
  68. Wells JM, Robinson K, Chamberlain LM, Schofield KM & Le Page RWF (1996) Lactic acid bacteria as vaccine delivery vehicles. Antonie van Leeuwenhoek 70: 317-330Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  1. 1.Department of Genetics, Groningen Biomolecular Sciences and Biotechnology InstituteUniversity of GroningenHarenThe Netherlands

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