Abstract
Bacterial Ghosts (BG) are empty cell envelopes of Gram-negative bacteria which have been produced by E-mediated lysis. BG are devoid of cytoplasmic content and in combination with the expression of the nuclease SNUC, BG are also devoid of chromosomal and plasmid DNA. Proof of concept and proof of principle studies showed that BG candidate vaccines are highly immunogenic and in many instances induce protective immunity against lethal challenge in animal models. Due to their nature of being bacterial envelope complexes, BG are endowed with intrinsic natural adjuvant activity. BG are able to stimulate the innate and adaptive immune system without any addition of exogenous adjuvants. Although the use of plasmid encoded genetic information is essential for the final make up of BG, BG are not to be considered as genetically manipulated organisms (GMO), as they are nonliving and devoid of genetic information. The latter aspect is of great importance for safety, as no pathogenic islands or antibiotic resistance cassettes can be transferred to other bacteria by horizontal gene transfer. This is an important difference to other chemical-, heat- and pressure- or radiation-inactivated vaccine candidates, which also very often need artificial adjuvants to be added to improve their immunogenicity. The final BG vaccine preparations are freeze dried and are stable for many years at ambient temperature. BG can also be used as carrier and delivery vehicles for drugs or active substances in tumor therapy and due to specific targeting of tumor cells allow a higher specificity of treatment and a reduction of the total amount of drug per application. As carrier of enzymatic activity BG can be used for a new concept of probiotics which can synthesise active compounds from substrates of the environment where they are applied with a certain preference for the gut system. Thus, BG represent a promising technology platform for novel vaccines including combination or DNA vaccines, as drug carriers for therapeutic approaches in tumor treatment and as novel probiotics.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Witte A, Wanner G, Bläsi U et al. Endogenous transmembrane tunnel formation mediated by phi X174 lysis protein E. J Bacteriol 1990; 172(7):4109–14.
Eko FO, Szostak MP, Wanner G et al. Production of Vibrio cholerae ghosts (VCG) by expression of a cloned phage lysis gene: potential for vaccine development. Vaccine 1994; 12(13):1231–7.
Jechlinger W, Szostak MP, Witte A et al. Altered temperature induction sensitivity of the lambda pR/cI857 system for controlled gene E expression in Escherichia coli. FEMS Microbiol Lett 1999; 173(2):347–52.
Jechlinger W, Szostak MP, Lubitz W. Cold-sensitive E-lysis systems. Gene 1998; 218(1–2):1–7.
Haidinger W, Szostak MP, Jechlinger W et al. Online monitoring of Escherichia coli ghost production. Appl Environ Microbiol 2003; 69(1):468–74.
Haidinger W, Mayr UB, Szostak MP et al. Escherichia coli ghost production by expression of lysis gene E and Staphylococcal nuclease. Appl Environ Microbiol 2003; 69(10):6106–13.
Riedmann EM et al. Bacterial ghosts as adjuvant particles. Expert Rev Vaccines 2007; 6(2):241–53.
Hensel A, van Leengoed LA, Szostak M et al. Induction of protective immunity by aerosol or oral application of candidate vaccines in a dose-controlled pig aerosol infection model. J Biotechnol 1996; 44(1–3):171–81.
Eko FO, Schukovskaya T, Lotzmanova EY et al. Evaluation of the protective efficacy of Vibrio cholerae ghost (VCG) candidate vaccines in rabbits. Vaccine 2003; 21(25–26):3663–74.
Mayr UB, Haller C, Haidinger W et al. Bacterial ghosts as an oral vaccine: a single dose of Escherichia coli O157∶H7 bacterial ghosts protects mice against lethal challenge. Infect Immun 2005; 73(8):4810–7.
Mayr UB, Haller C, Haidinger W et al. Mucosal single dose immunization of mice with Escherichia coli O157∶H7 bacterial ghosts protects against lethal challenge. J Immunol, submitted 2007.
Witte A, Bläsi U, Halfmann G et al. Phi X174 protein E-mediated lysis of Escherichia coli. Biochimie 1990; 72(2–3):191–200.
Witte A, Lubitz W. Biochemical characterization of phi X174-protein-E-mediated lysis of Escherichia coli. Eur J Biochem 1989; 180(2):393–8.
Witte A, Brand E, Mayrhofer P et al. Mutations in cell division proteins FtsZ and FtsA inhibit phiX174 protein-E-mediated lysis of Escherichia coli. Arch Microbiol 1998; 170(4):259–68.
Witte A, Schrot G, Schön P et al. Proline 21, a residue within the alpha-helical domain of phiX174 lysis protein E, is required for its function in Escherichia coli. Mol Microbiol 1997; 26(2):337–46.
Witte A, Lubitz W, Bakker EP. Proton-motive-force-dependent step in the pathway to lysis of Escherichia coli induced by bacteriophage phi X174 gene E product. J Bacteriol 1987; 169(4):1750–2.
Halfmann G. Different sensitivity of autolytic deficient Escherichia coli mutants to the mode of induction. FEMS Microbiology Letters 1984; 24:205–208.
Lubitz W, Halfmann G, Plapp R. Lysis of Escherichia coli after infection with phiX174 depends on the regulation of the cellular autolytic system. J Gen Microbiol 1984; 130(Pt 5):1079–87.
Mayr UB, Walcher P, Azimpour C et al. Bacterial ghosts as antigen delivery vehicles. Adv Drug Deliv Res 2005; 57(9):1381–91.
Eko FO, Mayr UB, Attridge SR et al. Characterization and immunogenicity of Vibrio cholerae ghosts expressing toxin-coregulated pili. J Biotechnol 2000; 83(1–2):115–23.
Kuen B, Lubitz W. Analysis of S-lyer proteins and genes in Crystalline Bacterial Cell Surface Proteins 1996; 77–102.
Szostak M, Auer T, Lubitz W. Immune response against recombinant bacterial ghosts, in Vaccines Cold Spring Harbor Laboratory Press 1993; 93:419–425.
Kuen B, Sleytr UB, Lubitz W. Sequence analysis of the sbsA gene encoding the 130-kDa surface-layer protein of Bacillus stearothermophilus strain PV72. Gene 1994; 145(1):115–20.
Khan AS, Mujer CV, Alefantis TG et al. Proteomics and bioinformatics strategies to design counter-measures against infectious threat agents. J Chem Inf Model 2006; 46(1):111–5.
Eko FO, He Q, Brown T et al. A novel recombinant multisubunit vaccine against Chlamydia. J Immunol 2004; 173(5):3375–82.
Lubitz P et al. Bacterial ghosts as a delivery system for zona pellucida-2 fertility control vaccines for brushtail possums (trichosurus vulpecula). Vaccine, submitted 2007.
Paukner S et al. DNA-loaded bacterial ghosts efficiently mediate reporter gene transfer and expression in macrophages. Mol Ther 2005; 11(2):215–23.
Kudela P, Paukner S, Mayr UB et al. Bacterial ghosts as novel efficient targeting vehicles for DNA delivery to the human monocyte-derived dendritic cells. J Immunother; 2005; 28(2):136–43.
Ebensen T, Paukner S, Link C et al. Bacterial ghosts are an efficient delivery system for DNA vaccines. J Immunol 2004; 172(11):6858–65.
Mayrhofer P, Tabrizi CA, Walcher P et al. Immobilization of plasmid DNA in bacterial ghosts. J Control Release 2005; 102(3):725–35.
Jechlinger W, Azimpour Tabrizi C, Lubitz W et al. Minicircle DNA immobilized in bacterial ghosts: in vivo production of safe nonviral DNA delivery vehicles. J Mol Microbiol Biotechnol 2004; 8(4):222–31.
Brady MS, Lee F, Petrie H et al. CD4(+) T-cells kill HLA-class-II-antigen-positive melanoma cells presenting peptide in vitro. Cancer Immunol Immunother 2000; 48(11):621–6.
Curiel-Lewandrowski C, Demierre MF. Advances in specific immunotherapy of malignant melanoma. J Am Acad Dermatol 2000; 43(2 Pt 1): 167–85; quiz 186–8.
Kudela P et al. Effective gene transfer to meanoma cells using bacterial ghosts. Cancer Letters 2007; in press.
Paukner S, Kohl G, Lubitz W. Bacterial ghosts as novel advanced drug delivery systems: antiproliferative activity of loaded doxorubicin in human Caco2 cells. J Control Release 2004; 94(1):63–74.
Huter V, Szostak MP, Gampfer J et al. Bacterial ghosts as drug carrier and targeting vehicles. J Control Release 1999; 61(1–2):51–63.
Hatfaludi T, Liska M, Zellinger D et al. Bacterial ghost technology for pesticide delivery. J Agric Food Chem 2004; 52(18):5627–34.
Maratea D, Young K, Young R. Delection and fusion analysis of the phage phi X174 lysis gene E. Gene 1985; 40(1):39–46.
Bahl H, Scholz H, Bayan N et al. Molecular biology of S-layers. FEMS Microbiol Rev 1997; 20(1–2):47–98.
Paukner S, Kohl G, Jalava K et al. Sealed bacterial ghosts—novel targeting vehicles for advanced drug delivery of water-soluble substances. J Drug Target 2003; 11(3):151–61.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Lubitz, P., Mayr, U.B., Lubitz, W. (2009). Applications of Bacterial Ghosts in Biomedicine. In: Guzmán, C.A., Feuerstein, G.Z. (eds) Pharmaceutical Biotechnology. Advances in Experimental Medicine and Biology, vol 655. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1132-2_12
Download citation
DOI: https://doi.org/10.1007/978-1-4419-1132-2_12
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-1131-5
Online ISBN: 978-1-4419-1132-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)