Skip to main content

Advertisement

SpringerLink
Log in

Type III Secretion, Contact-dependent Model for the Intracellular Development of Chlamydia

  • Original Paper
  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

The medically significant genus Chlamydia is a class of obligate intracellular bacterial pathogens that replicate within vacuoles in host eukaryotic cells termed inclusions. Chlamydia's developmental cycle involves two forms; an infectious extracellular form, known as an elementary body (EB), and a non-infectious form, known as the reticulate body (RB), that replicates inside the vacuoles of the host cells. The RB surface is covered in projections that are in intimate contact with the inclusion membrane. Late in the developmental cycle, these reticulate bodies differentiate into the elementary body form. In this paper, we present a hypothesis for the modulation of these developmental events involving the contact-dependent type III secretion (TTS) system. TTS surface projections mediate intimate contact between the RB and the inclusion membrane. Below a certain number of projections, detachment of the RB provides a signal for late differentiation of RB into EB. We use data and develop a mathematical model investigating this hypothesis. If the hypothesis proves to be accurate, then we have shown that increasing the number of inclusions per host cell will increase the number of infectious progeny EB until some optimal number of inclusions. For more inclusions than this optimum, the infectious yield is reduced because of spatial restrictions. We also predict that a reduction in the number of projections on the surface of the RB (and as early as possible during development) will significantly reduce the burst size of infectious EB particles. Many of the results predicted by the model can be tested experimentally and may lead to the identification of potential targets for drug design.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aldous, M.B., Grayston, J.T., Wang, S.P., Foy, H.M., 1992. Seroepidemiology of Chlamydia pneumoniae TWAR infection in Seattle families, 1966–1979. Infect. Dis. 166, 646.

    Google Scholar 

  • Bavoil, P., Hsia, R.C., Ojcius, D.M., 2000. Closing in on Chlamydia and its intracellular bag of tricks. Microbiology 146, 2723.

    Google Scholar 

  • Bavoil, P.M., Hsia, R.C., 1998. Type III secretion in Chlamydia. A case of déjà vu? Mol. Microbiol. 28, 860.

  • Campbell, L.A., Kuo, C.C., 2003. Chlamydia pneumoniae and atherosclerosis. Semin. Respir. Infect. 18, 48.

    Article  Google Scholar 

  • Fields, K.A., Hackstadt, T., 2000. Evidence for the secretion of Chlamydia trachomatis CopN by a type III secretion mechanism, Mol. Microbiol. 38, 1048.

    Google Scholar 

  • Fields, K.A., Mead, D.J., Dooley, C.A., Hackstadt, T., 2003. Chlamydia trachomatis type III secretion: evidence for a functional apparatus during early-cycle development, Mol. Microbiol. 48, 671.

    Google Scholar 

  • Forsberg, A., Viitanen, A.M., Skurnik, M., Wolf-Watz, H., 1991. The surface-located YopN protein is involved in calcium signal transduction in Yersinia pseudotuberculosis. Mol. Microbiol. 5, 977.

    Article  Google Scholar 

  • Hackstadt, T., Fischer, E.R., Scidmore, M.A., Rockey, D.D., Heinzen, R.A., 1997. Origins and functions of the chlamydial inclusion. Trends Microbiol. 5, 288.

    Article  Google Scholar 

  • Hackstadt, T., Scidmore-Carlson, M., Shaw, E., Fischer, E., 1999. The Chlamydia trachomatis IncA protein is required for homotypic vesicle fusion. Cell Microbiol. 1, 119.

    Article  Google Scholar 

  • Hensel, M., Shea, J.E., Waterman, S.R., Mundy, R., Nikolaus, T., Banks, G., Vazquez-Torres, A., Gleeson, C., Fang, F.C., Holden, D.W., 1998. Genes encoding putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2 are required for bacterial virulence and proliferation in macrophages. Mol. Microbiol. 30, 163.

    Article  Google Scholar 

  • Horn, M., Collingro, A., Schmitz-Esser, S., Beier, C.L., Purkhold, U., Fartmann, B., Brandt, P., Nyakatura, G.J., Droege, M., Frishman, D., Rattei, T., Mewes, H.W., Wagner, M., 2004. Illuminating the evolutionary history of chlamydiae. Science 304, 728.

    Article  Google Scholar 

  • Hsia, R.C., Pannekoek, Y., Ingerowski, E., Bavoil, P.M., 1997. Type III secretion genes identify a putative virulence locus of Chlamydia, Mol. Microbiol. 25, 351.

    Google Scholar 

  • Hueck, C.J., 1998. Type III protein secretion systems in bacterial pathogens of animals and plants, Microbiol. Mol. Biol. Rev. 62, 379.

    Google Scholar 

  • Johnson, F.W.A., Chancerelle, L.Y.J., Hobson, D., 1978. An improved method for demonstrating the growth of chlamydiae in tissue culture. Med. Lab. Sci. 35, 67.

    Google Scholar 

  • Kalman, S., Mitchell, W., Marathe, R., Lammel, C., Fan, J., Hyman, R.W., Olinger, L., Grimwood, J., Davis, R.W., Stephens, R.S., 1999. Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nat. Genet. 21, 385.

    Article  Google Scholar 

  • Mathews, S.A., Volp, K.M., Timms, P., 1999. Development of a quantitative gene expression assay for Chlamydia trachomatis identified temporal expression of σ factors. FEBS Lett. 458, 354.

    Article  Google Scholar 

  • Matsumoto, A., 1973. Fine structures of cell envelopes of Chlamydia organisms as revealed by freeze-etching and negative staining techniques. J. Bacteriol. 116, 1355.

    Google Scholar 

  • Matsumoto, A., 1981a. Electron Microscopic Observations of surface projections and related intracellular structures of Chlamydia organisms. J. Electron. Microsc. 30, 315.

    Google Scholar 

  • Matsumoto, A., 1981b. Isolation and electron microscopic observations of intracytoplasmic inclusions containing Chlamydia psittaci. J. Bacteriol. 145, 605.

    Google Scholar 

  • Matsumoto, A., 1982. Electron microscopic observations of surface projections on Chlamydia psittaci reticulate bodies. J. Bacteriol. 150, 358.

    Google Scholar 

  • Matsumoto, A., Bessho, I., Uchira, K., Suda, T., 1991. Morphological studies of the association of mitochondria with chlamydial inclusions and the fusion of chlamydial inclusions, J. Electron. Micro. 40, 356.

    Google Scholar 

  • Matsumoto, A., Fujiwara, E., Higashi, N., 1976. Observations of the surface projections of infectious small cell of Chlamydia psittaci in thin sections. J. Electron. Microsc. 25, 169.

    Google Scholar 

  • Matsumoto, A., Higashi, N., Tamura, A., 1973. Electron microscope observations on the effects of polymixin B sulfate on cell walls of Chlamydia psittaci. J. Bacteriol. 113, 357.

    Google Scholar 

  • Moulder, J.W., 1991. Interaction of chlamydiae and host cells in vitro. Microbiol. Rev. 55, 143.

    Google Scholar 

  • Read, T.D., Brunham, R.C., Shen, C., Gill, S.R., Heidelberg, J.F., White, O., Hickey, E.K., Peterson, J., Utterback, T., Berry, K., Bass, S., Linher, K., Weidman, J., Khouri, H., Craven, B., Bowman, C., Dodson, R., Gwinn, M., Nelson, W., DeBoy, R., Kolonay, J., McClarty, G., Salzberg, S.L., Eisen, J., Fraser, C.M., 2000. Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39. Nucleic Acids Res. 28, 1397.

    Article  Google Scholar 

  • Read, T.D., Myers, G.S., Brunham, R.C., Nelson, W.C., Paulsen, I.T., Heidelberg, J., Holtzapple, E., Khouri, H., Federova, N.B., Carty, H.A., Umayam, L.A., Haft, D.H., Peterson, J., Beanan, M.J., White, O., Salzberg, S.L., Hsia, R.C., McClarty, G., Rank, R.G., Bavoil, P.M., Fraser, C.M., 2003. Genome sequence of Chlamydophila caviae (Chlamydia psittaci GPIC): Examining the role of niche-specific genes in the evolution of the Chlamydiaceae. Nucleic Acids Res. 31, 2134.

    Article  Google Scholar 

  • Rockey, D.D., Matsumoto, A., 1999. The chlamydial developmental cycle. In: Brun, Y.V., Shimkets, L.J. (Eds.), Prokaryotic Development. ASM Press, Washington, DC, pp. 403–425.

    Google Scholar 

  • Shaw, E.I., Dooley, C.A., Fischer, E.R., Scidmore, M.A., Fields, K.A., Hackstadt, T., 2000. Three temporal classes of gene expression during the Chlamydia trachomatis developmental cycle. Mol. Microbiol. 37, 913.

    Article  Google Scholar 

  • Shirai, M., Hirakawa, H., Kimoto, M., Tabuchi, M., Kishi, F., Ouchi, K., Shiba, T., Ishii, K., Hattori, M., Kuhara, S., Nakazawa, T., 2000. Comparison of whole genome sequences of Chlamydia pneumoniae J138 from Japan and CWL029 from USA. Nucleic Acids Res. 28, 2311.

    Article  Google Scholar 

  • Spears, P., Storz, J., 1979. Biotyping of Chlamydia psittaci based on inclusion morphology and response to diethylaminoethyl-dextran and cycloheximide. Infect. Immun. 24, 224.

    Google Scholar 

  • Stephens, R.S., Kalman, S., Lammel, C., Fan, J., Marathe, R., Aravind, L., Mitchell, W., Olinger, L., Tatusov, R.L., Zhao, Q., Koonin, E.V., Davis, R.W., 1998. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 638.

    Article  Google Scholar 

  • Suchland, R.J., Rockey, D.D., Bannantine, J.P., Stamm, W.E., 2000. Isolates of Chlamydia trachomatis that occupy non-fusogenic inclusions lack IncA, a protein localized to the inclusion membrane. Infect. Immun. 68, 360.

    Google Scholar 

  • Tamura, A., Matsumoto, A., Manire, G.P., Higashi, N., 1971. Electron microscopic observations on the structure of the envelopes of mature elementary bodies and developmental reticulate forms of Chlamydia psittaci. J. Bacteriol. 105, 355.

    Google Scholar 

  • Thylefors, B., Negral, A. D., Parajasegaram, R., Dadzie, K. Y., 1995. Global data on blindness. Bull. World Health Org. 73, 115.

    Google Scholar 

  • Ward, M., 1995. The immunobiology and immunopathology of chlamydial infections. APMIS 103, 769.

    Article  Google Scholar 

  • Ward, M.E., 1983. Cqhlamydial classification, development and structure. Br. Med. Bull. 39, 109.

    Google Scholar 

  • Wilson, D.P., Mathews, S., Wan, C., Pettitt, A.N., McElwain, D.L.S., 2004. Use of a quantitative gene expression array based on micro-array techniques and a mathematical model for the investigation of chlamydial generation time. Bull. Math. Biol. 66, 523.

    Article  MathSciNet  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia

    D. P. Wilson & D. L. S. Mcelwain

  2. Department of Biomathematics, University of California, Los Angeles, CA, USA

    D. P. Wilson

  3. School of Life Sciences, Queensland University of Technology, Brisbane, Australia

    P. Timms

  4. Department of Biomedical Sciences, University of Maryland Dental School, Baltimore, MD, USA

    P. M. Bavoil

Authors
  1. D. P. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Timms
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. L. S. Mcelwain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. M. Bavoil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. P. Wilson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilson, D.P., Timms, P., Mcelwain, D.L.S. et al. Type III Secretion, Contact-dependent Model for the Intracellular Development of Chlamydia . Bltn. Mathcal. Biology 68, 161–178 (2006). https://doi.org/10.1007/s11538-005-9024-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11538-005-9024-1

Keywords

Search

Navigation