Roles of YopN, LcrG and LcrV in Controlling Yops Secretion by Yersinia pestis

  • Mohamad A. Hamad
  • Matthew L. Nilles
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 603)

Control of Yops secretion in pathogenic Yersinia is achieved at several levels. These levels likely include transcriptional, post-transcriptional, translational and secretional controls. Secretion control appears to be mediated by two pathways. One pathway involves YopN and proteins that interact with YopN. The second pathway consists of LcrG and its interaction with LcrV. LcrV is a postive regulator of Yops secretion that exerts control over Yops secretion by negating the secretion blocking role of LcrG. However, the intersection of these two control pathways is not understood. Recent work has allowed the development of a speculative model that brings YopN-mediated and LcrG-LcrV-mediated control together in the context of the ability of the needle complex to respond to Ca2+.


Blocking Activity Yersinia Enterocolitica Yersinia Pestis Secretion Regulation Cytosolic Face 
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  1. Anderson, D.M., Ramamurthi, K.S., Tam, C. and Schneewind, O. (2002) YopD and LcrH regulate expression of Yersinia enterocolitica YopQ by a posttranscriptional mechanism and bind to yopQ RNA. J. Bacteriol. 184, 1287-1295.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Brubaker, R.R. (1972) The genus Yersinia: biochemistry and genetics of virulence. Curr. Top. Microbiol. Immunol. 57, 111-158.CrossRefPubMedGoogle Scholar
  3. Brubaker, R.R. (2003) Interleukin-10 and inhibition of innate immunity to Yersiniae: roles of Yops and LcrV (V antigen). Infect. Immun. 71, 3673-3681.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Cambronne, E.D. and Schneewind, O. (2002) Yersinia enterocolitica type III secretion: yscM1 and yscM2 regulate yop gene expression by a posttranscriptional mechanism that targets the 5' untranslated region of yop mRNA. J. Bacteriol. 184, 5880-93.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Cornelis, G.R. (1999) The Yersinia deadly kiss. J. Bacteriol. 180, 5495-5504.Google Scholar
  6. Day, J.B., Ferracci, F. and Plano, G.V. (2003). Translocation of YopE and YopN into eu-karyotic cells by Yersinia pestis yopN, tyeA, sycN, yscB and lcrG deletion mutants meas-ured using a phosphorylatable peptide tag and phosphospecific antibodies. Mol. Microbiol. 47, 807-823.CrossRefPubMedGoogle Scholar
  7. Day, J.B. and Plano, G.V. (1998) A complex composed of SycN and YscB functions as a specific chaperone for YopN in Yersinia pestis. Mol. Microbiol. 30, 777-788.CrossRefPubMedGoogle Scholar
  8. Ferracci, F., Day, J.B., Ezelle, H.J. and Plano, G.V. (2004) Expression of a functional secreted YopN-TyeA hybrid protein in Yersinia pestis is the result of a +1 translational frameshift event. J. Bacteriol. 186, 5160-5166.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Ferracci, F., Schubot, F.D., Waugh, D.S. and Plano, G.V. (2005) Selection and characteriza-tion of Yersinia pestis YopN mutants that constitutively block Yop secretion. Mol. Micro-biol. 57, 970-987.CrossRefGoogle Scholar
  10. Fields, K. A., Nilles, M.L., Cowan, C. and Straley, S.C. (1999) Virulence role of V antigen of Yersinia pestis at the bacterial surface. Infect. Immun. 67, 5395-5408.PubMedPubMedCentralGoogle Scholar
  11. Forsberg, Å., Viitanen, A.M., Skurnik, M. and Wolf-Watz, H. (1991) “The surface-located YopN protein is involved in calcium signal transduction in Yersinia pseudotuberculosis.” Mol. Microbiol. 5, 977-986.CrossRefPubMedGoogle Scholar
  12. Hamad, M.A. (2006) The roles of LcrG and LcrV in secretion control of Yops in Yersinia pestis. Ph.D. Dissertation, Department of Microbiology and Immunology, University of North Dakota, Grand Forks, ND, USA.Google Scholar
  13. Iriarte, M., Sory, M.-P., Boland, A., Boyd, A.P., Mills, S.D., Lambermont, I. and Cornelis, G.R. (1998) “TyeA, a protein involved in control of Yop release and in translocation of Yersinia Yop effectors.” EMBO J. 17, 1907-1918.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Jackson, M.W., Day, J.B. and Plano, G.V. (1998) YscB of Yersinia pestis functions as a spe-cific chaperone for YopN. J. Bacteriol. 180, 4912-4921.PubMedPubMedCentralGoogle Scholar
  15. Kenjale, R., Wilson, J., Zenk, S.F., Saurya, S., Picking, W.L. and Blocker, A. (2005) The needle component of the type III secreton of Shigella regulates the activity of the secretion apparatus. J. Biol. Chem. 280, 42929-42937.CrossRefPubMedGoogle Scholar
  16. Lawton, D.G., Longstaff, C., Wallace, B.A., Hill, J., Leary, S.E., Titball, R.W. and Brown, K.A. (2002) Interactions of the type III secretion pathway proteins LcrV and LcrG from Yersinia pestis are mediated by coiled-coil domains. J. Biol. Chem. 277, 38714-38722.CrossRefPubMedGoogle Scholar
  17. Lloyd, S.A., Norman, M., Rosqvist, R. and Wolf-Watz, H. (2001) Yersinia YopE is targeted for type III secretion by N-terminal, not mRNA, signals. Mol. Microbiol. 39, 520-532.CrossRefPubMedGoogle Scholar
  18. Matson, J.S. and Nilles, M.L. (2001). “LcrG-LcrV Interaction Is Required for Control of Yops Secretion in Yersinia pestis.” Journal of Bacteriology 183(17): 5082-91.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Matson, J.S. and Nilles, M.L. (2002) Interaction of the Yersinia pestis type III regulatory proteins LcrG and LcrV occurs at a hydrophobic interface. BMC Microbiol. 2, 16.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Michiels, T., Wattiau, P., Brasseur, R., Ruysschaert, J.M. and Cornelis, G. (1990) Secreation of Yop proteins by Yersiniae. Infect. Immun. 58, 2840-2849.PubMedPubMedCentralGoogle Scholar
  21. Mota, L.J. (2006. Type III secretion gets an LcrV tip. Trends Microbiol. 14, 197-200.CrossRefPubMedGoogle Scholar
  22. Mueller, C.A., Broz, P., Müller, S.A., Ringler, P., Erne-Brand, F., Sorg, I., Kuhn, M., Engel, A. and Cornelis, G.R. (2005). The V-antigen of Yersinia forms a distinct structure at the tip of injectisome needles. Science 310, 674-676.CrossRefPubMedGoogle Scholar
  23. Nilles, M.L., Fields, K.A. and Straley, S.C. (1998) The V antigen of Yersinia pestis regulates Yop vectorial targeting as well as Yop secretion through effects on YopB and LcrG. J. Bacteriol. 180, 3410-3420.PubMedPubMedCentralGoogle Scholar
  24. Nilles, M.L., Williams, A.W., Skrzypek, E. and Straley, S.C. (1997) Yersinia pestis LcrV forms a stable complex with LcrG and may have a secretion-related regulatory role in the low-Ca2+ response. J. Bacteriol. 179, 1307-1316.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Overheim, K.A., Depaolo, R.W., DeBord, K.L., MOrrin, E.M., Anderson, D.M., Green, N.M., Brubaker, R.R., Jabri, B. and Schneewind, O. (2005) LcrV plague vaccine with altered immunomodulatory properties. Infect. Immun. 73, 5152-5159.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Pallen, M.J., Francis, M.S. and Fütterer, K. (2003) Tetratricopeptide-like repeats in type-III-secretion chaperones and regulators. FEMS Microbiol. Lett. 223, 53-60.Google Scholar
  27. Perry, R.D. and Fetherson, J.D. (1997) Yersinia pestis — etiologic agent of plague. Clin. Microbiol. Rev. 10, 35-66.PubMedPubMedCentralGoogle Scholar
  28. Pettersson, J., Holmström, A. , Hill, J., Leary, S., Frithz-Lindsten, E., von Euler-Matell, A., Carlsson, E., Titball, R., Forsberg, Å. and Wolf-Watz, H. (1999) The V-antigen of Yersinia is surface-exposed before target cell contact and involved in virulence protein transloca-tion. Mol. Microbiol. 32, 961-976.CrossRefPubMedGoogle Scholar
  29. Rimpiläinen, M., Forsberg, Å. and Wolf-Watz, H. (1992) A novel protein, LcrQ, involved in the low-calcium response of Yersinia pseudotuberculosis, shows extensive homology to YopH. J. Bacteriol. 174, 3355-3363.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Rosqvist, R., Magnusson, K-E. and Wolf-Watz, H. (1994) Target cell contact triggers expres-sion and polarized transfer of Yersinia YopE cytotoxin into mammalian cells. EMBO J. 13, 964-972.PubMedPubMedCentralGoogle Scholar
  31. Sing, A., Reithmeier-Rost, D., Granfors, K., Hill, J., Roggenkamp, A. and Heesemann, J. (2005) A hypervariable N-terminal region of Yersinia LcrV determines Toll-like receptor 2-mediated IL-10 induction and mouse virulence. PNAS 102, 16049-16054.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Skrzypek, E. and Straley, S.C. (1993) LcrG, a secreted protein involved in negative regulation of the low-calcium response in Yersinia pestis. J. Bacteriol. 175, 3520-3528.CrossRefGoogle Scholar
  33. Skrzypek, E. and Straley, S.C. (1995) Differential effects of deletions in lcrV on secretion of V antigen, regulation of the low-Ca2+ response, and virulence of Yersinia pestis. J. Bacteriol. 177, 2530-2542.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Straley, S. (1988) The plasmid-encoded outer-membrane proteins of Yersinia pestis. Rev. Infect. Dis. 10, S323-S326.CrossRefPubMedGoogle Scholar
  35. Straley, S.C. and Bowmer, W.S. (1986) Virulence genes regulated at the transcriptional level by Ca2+ in Yersinia pestis include structural genes for outer membrane proteins. Infect. Immun. 51, 445-454.PubMedPubMedCentralGoogle Scholar
  36. Straley, S.C. and Perry, R.D. (1995) Environmental modulation of gene expression and patho-genesis in Yersinia. Trends Microbiol. 3, 310-317.CrossRefPubMedGoogle Scholar
  37. Straley, S.C., Plano, G.V., Skrzypek, E., Haddix, P.L. and Fields, K.A. (1993) Regulation by Ca2+ in the Yersinia low-Ca2+ response. Mol. Microbiol. 8, 1005-1010.CrossRefPubMedGoogle Scholar
  38. Titball, R.W. and Williamson, E.D. (2004) Yersinia pestis (plague) vaccines. Expert Opin. Biol. Ther. 4, 965-73.Google Scholar
  39. Torruellas, J., Jackson, M.W., Pennock, J.W. and Plano, G.V. (2005) The Yersinia pestis type III secretion needle plays a role in the regulation of Yop secretion. Mol. Microbiol. 57, 1719-1733.CrossRefPubMedGoogle Scholar
  40. Williams, A.W. and Straley, S.C. (1998) YopD of Yersinia pestis plays a role in the negative regulation of the low-calcium response in addition to its role in the translocation of Yops. J. Bacteriol. 180, 350-358.PubMedPubMedCentralGoogle Scholar
  41. Williamson, E.D., Flick-Smith, H.C., LeButt, C., Rowland, A., Jones, S.M., Waters, E.L., Gwyther, R.J., Miller, J., Packer, P.J. and Irving, M. (2005) Human immune response to a plague vaccine comprising recombinant F1 and V antigens. Infect. Immun. 73, 3598-3608.CrossRefPubMedPubMedCentralGoogle Scholar
  42. Wulff-Strobel, C.R., Williams, A.W. and Straley, S.C. (2002) LcrQ and SycH function to-gether at the Ysc type III secretion system in Yersinia pestis to impose a hierarchy of se-cretion. Mol. Microbiol. 43, 411-423.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Mohamad A. Hamad
    • 1
  • Matthew L. Nilles
    • 2
  1. 1.Department of MicrobiologyUniversity of Colorado Health Science CenterDenverUSA
  2. 2.Department of Microbiology and Immunology, School of Medicine and Health ScienceUniversity of North DakotaGrand ForksUSA

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