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Cascioferro, Alessandro (2008) Le proteine micobatteriche PE: localizzazione cellulare e possibile utilizzo per lo sviluppo di un sistema di antigen display. [Tesi di dottorato]

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Abstract (inglese)

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, a chronic infectious disease that is responsible for the death of over two million people each year.
The genome of Mtb strain H37Rv is made up of 4,411,529 nucleotides and encodes about 3986 proteins. One of the major surprise risen from the genome sequence, published in 1998, is the presence of two large unrelated families of proteins with unknown functions. These protein families are referred to as PE/PPE family of genes.
The PE family of Mycobacterium tuberculosis includes 98 proteins which share a highly homologous N-terminus sequence of about 110 amino acids (PE domain). Depending on the C-terminal domain, the PE family can be divided in three subfamilies, the largest of which is the PE_PGRS with 61 members.
In this study, we determined the cellular localization of three PE proteins by cell fractionation and immunoelectron microscopy by expressing chimeric epitope-tagged recombinant proteins in Mycobacterium smegmatis. We demonstrate that the PE domains of PE_PGRS33 and PE11 (a protein constituted by the only PE domain) contain the information necessary for cell wall localization, and that they can be used as fusion partners to deliver a sufficiently long C-terminus-linked protein domain on the mycobacterial cell surface. Indeed, we demonstrate that PE_PGRS33 and Rv3097c (a lipase belonging to the PE family) are surface exposed and localize in the mycobacterial cell wall. Moreover, we found that PE_PGRS33 is easily extractable by detergents suggesting its localization in the mycobacterial outer membrane. Beyond defining the cellular localization of these proteins, and a function for their PE domains, these data open the interesting possibility to construct recombinant mycobacteria expressing heterologous antigens on their surface for vaccine purposes.


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Tipo di EPrint:Tesi di dottorato
Relatore:Manganelli, Riccardo
Dottorato (corsi e scuole):Ciclo 20 > Corsi per il 20simo ciclo > VIROLOGIA E BIOTECNOLOGIE MICROBICHE
Data di deposito della tesi:2008
Anno di Pubblicazione:2008
Parole chiave (italiano / inglese):Mycobacterium tuberculosis, Vaccine, Cell wall, Cellular localization, PE protein family
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Struttura di riferimento:Dipartimenti > Dipartimento di Istologia, Microbiologia e Biotecnologie Mediche
Codice ID:677
Depositato il:10 Set 2008
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1. Abdallah AM, Verboom T, Hannes F, Safi M, Strong M, Eisenberg D, Musters RJ, Vandenbroucke-Grauls CM, Appelmelk BJ, Luirink J, Bitter W. (2006) A specific secretion system mediates PPE41 transport in pathogenic mycobacteria. Mol Microbiol 62: 667–679. Cerca con Google

2. Adindla, S., and Guruprasad, L. (2003) Sequence analysis corresponding to the PPE and PE proteins in Mycobacterium tuberculosis and other genomes. J Biosci 28:169–179. Cerca con Google

3. Agger EM, Andersen P. 2002. A novel TB vaccine; towards a strategy based on our understanding of BCG failure. Vaccine. 22;21(1-2):7-14. Cerca con Google

4. Andersen P. 2007. Tuberculosi vaccines-an update. Nature Reviews Microbiology 5, 484-487. Cerca con Google

5. Agger EM, Rosenkrands I, Olsen AW, Hatch G, Williams A, Kritsch C, Lingnau K, von Gabain A, Andersen CS, Korsholm KS, Andersen P. 2006. Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31. Vaccine. 29;24(26):5452-60. Cerca con Google

6. Balaji, K.N., Goyal, G., Narayana, Y., Srinivas, M., Chaturvedi, R., and Mohammad, S. (2007) Apoptosis triggered by Rv1818c, a PE family gene from Mycobacterium tuberculosis is regulated by mitochondrial intermediates in T cells. Microbes Infect 9: 271–281. Cerca con Google

7. Banu, S., Honore, N., Saint-Joanis, B., Philpott, D., Prevost, M.C., and Cole, S.T. (2002). Are the PE_PGRS proteins of Mycobacterium tuberculosis variable surface antigens ? Mol. Microbiol. 44, 9-19. Cerca con Google

8. Basu, S., Pathak, S.K., Banerjee, A., Pathak, S., Bhattacharyya, A., Yang, Z., et al. (2007) Execution of macrophage apoptosis by PE_PGRS33 of Mycobacterium tuberculosis is mediated by Toll-like receptor 2-dependent release of tumor necrosis factor-alpha. J Biol Chem 282: 1039–1050. Cerca con Google

9. Brennan, M.J., Delogu, G., Chen, Y., Bardarov, S., Kriakov, J., Alavi, M., and Jacobs, W.R., Jr. (2001) Evidence that mycobacterial PE_PGRS proteins are cell surface constituents that influence interactions with other cells. Infect Immun 69: 7326–7333. Cerca con Google

10. Brennan, M., J. et al (2004). PE and PPE multigene families of mycobacteria. Capitolo 33 tratto dal testo: “ Tuberculosis and the tubercle bacillus” Editors: Cole, S. T.et al. ASM Press. Washington. Cerca con Google

11. Brennan, M.J., and Delogu, G. (2002) The PE multigene family: a ‘molecular mantra’ for mycobacteria. Trends Microbiol 10: 246–249. Cerca con Google

12. Brennan P. J. (2003). Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (2003). 83, 91-97. Cerca con Google

13. Brennan PJ. et al., 1995. The envelope of mycobacteria. Annu. Rev. Biochem. 64:29-63. Cerca con Google

14. Brosch R, Gordon SV, Garnier T, Eiglmeier K, Frigui W, Valenti P, Dos Santos S, Duthoy S, Lacroix C, Garcia-Pelayo C, Inwald JK, Golby P, Garcia JN, Hewinson RG, Behr MA, Quail MA, Churcher C, Barrell BG, Parkhill J, Cole ST. 2007. Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci U S A. 27;104(13):5596-601. Cerca con Google

15. Cascioferro A, Delogu G, Colone M, Sali M, Stringaro A, Arancia G, Fadda G, Palù G, Manganelli R. (2007). PE is a functional domain responsible for protein translocation and localization on mycobacterial cell wall. Mol Microbiol. 66(6):1536-47. Cerca con Google

16. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG. (1998). Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 393, 537–544. Cerca con Google

17. Cole, S. T. (2002). Comparative and functional genomics of the Mycobacterium tuberculosis complex .Microbiology. 148, 2919-2928. Cerca con Google

18. Cole, S. T. ,and Barrell,B.G. (1998). Analysis of the genome of Mycobacterium tuberculosis H37Rv. Genet. Tuberculosis. ( Novartis Found Symp) 217, 160-172. Cerca con Google

19. Corbett, L. and Raviglione, M.(2005). Tuberculosis and the Tubercle Bacillus cap.1, ASM press. Cerca con Google

20. Cowan SW, Schirmer T, Rummel G, Steiert M, Ghosh R, Pauptit RA, Jansonius JN, Rosenbusch JP. 1992. Crystal structures explain functional properties of two E. coli porins. Nature. 358:727-33. Cerca con Google

21. Deb, C., Daniel, J., Sirakova, T.D., Abomoelak, B., Dubey, V.S., and Kolattukudy, P.E. (2006) A novel lipase belonging to the hormone-sensitive lipase family induced under starvation to utilize stored triacylglycerol in Mycobacterium tuberculosis. J Biol Chem 281: 3866–3875. Cerca con Google

22. Delogu, G., Pusceddu, C., Bua, A., Fadda, G., Brennan, M.J., and Zanetti, S.(2004). Rv1818c-encoded PE_PGRS protein of Mycobacterium tuberculosis is surface exposed and influences bacterial cell structure.Mol.Microbiol.52, 725-733. Cerca con Google

23. Dheenadhayalan, V., Delogu, G., and Brennan, M.J. (2006). Expression of the PE_PGRS 33 protein in Mycobacterium smegmatis triggers necrosis in macrophages and enhanced mycobacterial survival. Microbes Infect 8: 262–272. Cerca con Google

24. Dietrich J, Andersen C, Rappuoli R, Doherty TM, Jensen CG, Andersen P. 2006. Mucosal administration of Ag85B-ESAT-6 protects against infection with Mycobacterium tuberculosis and boosts prior bacillus Calmette-Guerin immunity. J Immunol. 1;177(9):6353-60. Cerca con Google

25. Engelhardt H, Heinz C, Niederweis M. 2002. A tetrameric porin limits the cell wall permeability of Mycobacterium smegmatis. J Biol Chem. 4;277:37567-72. Cerca con Google

26. Engleberg N. Cary, DiRita V., Dermody T.S. (2006). Mechanisms of microbial disease 4° edizione LWW editore. Capitolo 23. Cerca con Google

27. Fine PE. 1995. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 18;346(8986):1339-45. Cerca con Google

28. Gey van Pittius, N.C., Sampson, S.L., Lee, H., Kim, Y., van Helden, P.D., and Warren, R.M. (2006). Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions. BMC Evol Biol 6: 95. Cerca con Google

29. Gomez, J. and McKinney J. (2004). Mycobacterium tuberculosis persistence, latency, and drug tolerance. Tuberculosis. 84, 29-44. Cerca con Google

30. Grode, L., Kursar, M., Fensterle, J., Kaufmann, S.H., and Hess, J. (2002) Cell-mediated immunity induced by recombinant Mycobacterium bovis Bacille Calmette-Guerin strains against an intracellular bacterial pathogen: importance of antigen secretion or membrane-targeted antigen display as lipoprotein for vaccine efficacy. J Immunol 168: 1869–1876. Cerca con Google

31. Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Nasser Eddine A, Mann P, Goosmann C, Bandermann S, Smith D, Bancroft GJ, Reyrat JM, van Soolingen D, Raupach B, Kaufmann SH. 2005. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette- Guérin mutants that secrete listeriolysin. J Clin Invest. 115(9):2472-9. Cerca con Google

32. Heinz, C., and Niederweis, M. (2000) Selective extraction and purification of a mycobacterial outer membrane protein. Anal Biochem 285: 113–120. Cerca con Google

33. Hong, X., and Hopfinger, A.J. (2004) Molecular modelling and simulation of Mycobacterium tuberculosis cell wall permeability. Biomacromolecules 5:1066– 1077. Cerca con Google

34. Horwitz MA, Harth G. 2003. A new vaccine against tuberculosis affords greater survival after challenge than the current vaccine in the guinea pig model of pulmonary tuberculosis. Infect Immun. 71(4):1672-9. Cerca con Google

35. Jackson M., Stadthagen G and Gicquel B. (2007) Long-chain multiple methylbranched fatty acid-containing lipids of Mycobacterium tuberculosis: biosynthesis, transport, regulation and biological activities. Tuberculosis 87(2):78- 86. Cerca con Google

36. Kartmann B, Stenger S, Niederweis M. 1999. Porins in the cell wall of Mycobacterium tuberculosis. J Bacteriol. 181(20):6543-6. Cerca con Google

37. Kessel M, Brennan MJ, Trus BL, Bisher ME, Steven AC. 1998. Naturally crystalline porin in the outer membrane of Bordetella pertussis. J Mol Biol. 5;203(1):275-8. Cerca con Google

38. Koch R. (1882). Die Aetiogie der Tubercolose. Berl.Klin.Wochensschr.19, 21- 230. Cerca con Google

39. Koebnik R, Locher KP, Van Gelder P. 2000. Structure and function of bacterial outer membrane proteins: barrels in a nutshell. Mol Microbiol. 37(2):239-53. Cerca con Google

40. Kolattukudy P. E., Fernandes N. D., Azad A. K., Fitzmaurice A. M. e Sirakova T. D. (1997) Biochemistry and molecular genetics of cell-wall lipid biosynthesis in mycobacteria. Molecular Microbiology. 24, 263-270. Cerca con Google

41. La Placa M. (2005). Principi di microbiologia medica. Esculapio (X°edizione), 2005. Cerca con Google

42. Lichtinger T, Heym B, Maier E, Eichner H, Cole ST, Benz R. 1999. Evidence for a small anion-selective channel in the cell wall of Mycobacterium bovis BCG besides a wide cation-selective pore. FEBS Lett. 9;454(3):349-55. Cerca con Google

43. Liu J., Barry C.E. (1999). Cell wall: physical structure and permeability. Mycobacteria, molecular biology and virulence. Colin R. (1999).12: 220-236. Cerca con Google

44. Mahfoud, M., Sukumaran, S., Hulsmann, P., Grieger, K., and Niederweis, M. (2006) Topology of the porin MspA in the outer membrane of Mycobacterium smegmatis. J Biol Chem 281: 5908–5915. Cerca con Google

45. Minnikin, D.E. (1982) Lipids: Complex lipids, their chemistry, biosynthesis and roles. In The Biology of the Mycobacteria: Physiology, Identification and Classification. Ratledge, C. and Stanford, J. (eds). London: Academic Press, pp. 95-184. Cerca con Google

46. Murray,P. R. et al. (2005). Medical Microbiology. 5th edition.Univ. of Maryland, Baltimore, Brandon-Hill, cap.40. Cerca con Google

47. Niederweis M, Ehrt S, Heinz C, Klöcker U, Karosi S, Swiderek KM, Riley LW, Benz R. 1999. Cloning of the mspA gene encoding a porin from Mycobacterium smegmatis. Mol Microbiol. 33:933-45. Cerca con Google

48. Niederweis M. (2003). Mycobaterial porins- new channel proteins in inique outer membranes. Molecular Microbiology 49:1167-1177. Cerca con Google

49. Ortalo- Magnè A., Dupont M. A., Lemassu A., Andersen Å., Gounon P., Daffè M. (1995). Molecular composition of the outermost capsular material of the tubercle bacillus. Microbiology (1995). 141, 1609-1620. Cerca con Google

50. Ramakrishnan, L. et al. (2000). Granuloma-specific expression of mycobacterium virulence proteins from the glycine–rich PE_PGRS family. Science 288, 1436-1439. Cerca con Google

51. Richeldi L., Fabbri L., Grassi C. (2003). La tubercolosi agli inizi del XXI secolo: diagnosi e terapia. (Dossier), Clinica delle malattie dell’apparato respiratorio Università di Modena e Reggio Emilia,Università di Pavia. Cerca con Google

52. Rousseau C., Winter N., Pivert E., Bordat Y., Neyrolles O., Avé P., Huerre M., Gicquel B., Jackson M. (2004). Production of phthiocerol dimycocerosates protects Mycobacterium tuberculosis from the cidal activity of reactive nitrogen intermediates produced by macrophages and modulates the early immune response to infection. Cell Microbiol. 6:277-87. Cerca con Google

53. Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. Cerca con Google

54. Sampson S.L., P. Lukey, R.M.Warren, P.D. van Helden, M.Richardson, and M.j. Everett. Expression, characterization and subcellular localization of the Mycobacterium tuberculosis PPE gene Rv1917c. Tuberculosis 81:305-317. 2001. Cerca con Google

55. Snapper, S.B., Melton, R.E., Mustafa, S., Kieser, T., and Jacobs, W.R., Jr (1990) Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis. Mol Microbiol 4: 1911–1919. Cerca con Google

56. Stahl C, Kubetzko S, Kaps I, Seeber S, Engelhardt H, Niederweis M. 2001. MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatis. Mol Microbiol. 40:451-64. Cerca con Google

57. Strong, M., Sawaya, M.R., Wang, S., Phillips, M., Cascio, D., and Eisenberg, D. (2006) Toward the structural genomics of complexes: crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis. Proc Natl Acad Sci USA 103: 8060–8065. Cerca con Google

58. Tokuyasu, K.T. (1973) A technique for ultracryotomy of cell suspensions and tissues. J Cell Biol 57: 551–565. Cerca con Google

59. Tundup, S., Akhter, Y., Thiagarajan, D., and Hasnain, S.E. (2006) Clusters of PE and PPE genes of Mycobacterium tuberculosis are organized in operons: evidence that PE Rv2431c is co-transcribed with PPE Rv2430c and their gene products interact with each other. FEBS Lett 580:1285–1293. Cerca con Google

60. World Heath Organization www.who.int Vai! Cerca con Google

61. http://genolist.pasteur.fr/TubercuList/ Vai! Cerca con Google

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