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Modelling the Onset of Virulence in Pathogenic Bacteria

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Bacterial Molecular Networks

Part of the book series: Methods in Molecular Biology ((MIMB,volume 804))

Abstract

Bacterial virulence is a multifactorial process. In this chapter, we review some known mechanisms used by bacteria to trigger their production of virulence factors. We develop the idea that although the onset of virulence shows up an abrupt transition, the modelling of this dynamics can be classified in two qualitatively distinct infectious transitions which are respectively called “shift” or “switch.” We review methods enabling one to determine the types of behaviour that can be exhibited by a given model and we consider applications in three cases of virulence factor regulation. We conclude that in most cases a “successful” infection would require that the onset of virulence follows an irreversible switch behaviour.

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References

  1. Weinberg ED. (2009) Iron availability and infection. BBA, 1790:600–605.

    CAS  Google Scholar 

  2. Expert D. (1999) Withholding and exchanging iron: interactions between Erwinia spp. and their plant hosts. Annu Rev Phytopathol, 37:307–334.

    Article  PubMed  CAS  Google Scholar 

  3. Gerlach RG, Hensel M. (2007) Protein secretion systems and adhesins: the molecular armory of gram-negative pathogens. Int J Med Microbiol, 297:401–415.

    CAS  Google Scholar 

  4. Cornelis GR, Van Gijsegem F. (2000) Assembly and function of type III secretory systems. Ann Rev Microbiol, 54:735–774.

    Article  CAS  Google Scholar 

  5. Backert S, Meyer TF. (2006) Type IV secretion systems and their effectors in bacterial pathogenesis. Curr Opin Microbiol, 9:207–217.

    Article  PubMed  CAS  Google Scholar 

  6. Lazdunski AM, Ventre I, Sturgis JN. (2004) Regulatory circuits and communication in gram-negative bacteria. Nature, 2:581–592.

    CAS  Google Scholar 

  7. Dayan F, Monticelli M, Pouysségur J, Pécou E. (2009) Gene regulation in response to graded hypoxia: the non-redundant roles of the oxygen sensors PHD and FIH in the HIF pathway. J Theor Biol, 259:304–316.

    Article  CAS  Google Scholar 

  8. Mitrophanov AY, Groisman EA. (2008) Positive feedback in cellular control systems. Bioessays, 30(6):542–555.

    CAS  Google Scholar 

  9. Mitrophanov AY, Churchward G, Borodovsky M. (2007) Control of Streptococcus pyogenes virulence: modeling of the CovR/S signal transduction system. J Theor Biol, 246: 113–128.

    CAS  Google Scholar 

  10. Gardner TS, Cantor CR, Collins JJ. (2000) Construction of a genetic toggle switch in Escherichia coli. Nature, 403:339–342.

    CAS  Google Scholar 

  11. Boots M, Hudson PJ, Sasaki A. (2004) Large shifts in pathogen virulence relate to host population structure. Science, 303:842–844.

    CAS  Google Scholar 

  12. Bagowski CP, Ferrell JE Jr. (2001) Bistability in the JNK cascade. Curr Biol, 11:1176–1182.

    Article  CAS  Google Scholar 

  13. Sepulchre JA, Reverchon S, Nasser W. (2007) Modeling the onset of virulence in a pectinolytic bacterium. J Theor Biol, 244:239–257.

    Article  CAS  Google Scholar 

  14. Edited by Thomas R. (1981) On the Relation Between the Logical Structure of Systems and Their Ability to Generate Multiple Steady States and Sustained Oscillations, volume 9. Springer, 180–193.

    Google Scholar 

  15. Griffith JS. (1968) Mathematics of cellular control processes. II. Positive feedback to one gene. J Theor Biol, 20:209–216.

    CAS  Google Scholar 

  16. Ferrell JE Jr, Xiong W. (2001) Bistability in cell signaling: how to make continuous processes discontinuous and reversible processes irreversible. Chaos, 11:227–236.

    CAS  Google Scholar 

  17. Hasty J, McMillen D, Isaacs F, Collins JJ. (2001) Computational studies of gene regulatory networks: in numero molecular biology. Nat Rev Genet, 2:268–279.

    Article  CAS  Google Scholar 

  18. Engelborghs K, Luzyanina T, Roose D. (2002) Numerical bifurcation analysis of delay differential equations using DDE-BIFTOOL. ACM Trans Math Softw, 28(1):1–21.

    Article  Google Scholar 

  19. Dhooge A, Govaerts W, Kuznetsov YA. (2003) MATCONT: a MATLAB package for numerical bifurcation analysis of ODEs. ACM Trans Math Softw, 29(2):141–164.

    Article  Google Scholar 

  20. Strogatz S. (2001). Nonlinear Dynamics and Chaos: With Applications to Physics, Biology, Chemistry, and Engineering (Studies in Nonlinearity). Perseus Books Group.

    Google Scholar 

  21. Angeli D, Ferrell JE Jr, Sontag ED. (2004) Detection of multistability, bifurcations and hysteresis in a large class of biological positive-feedback systems. PNAS, 101(7):1822–1827.

    Article  PubMed  CAS  Google Scholar 

  22. Hugouvieux-Cotte-Pattat N, Condemine G, Nasser W, Reverchon S. (1996) Regulation of pectinolysis in Erwinia chrysanthemi. Annu Rev Microbiol, 50:213–257.

    CAS  Google Scholar 

  23. Lebeau A, Reverchon S, Gaubert S, Kraepiel Y, Simond-Côte E, Nasser W, Van Gijsegem F. (2008) The GacA global regulator is required for the appropriate expression of Erwinia chrysanthemi 3937 pathogenicity genes during plant infection. Environ Microbiol, 10: 545–559.

    Article  PubMed  CAS  Google Scholar 

  24. Reverchon S, Expert D, Robert-Baudouy J, Nasser W. (1997) The cyclic AMP receptor protein is the main activator of pectinolysis genes in Erwinia chrysanthemi. J Bacteriol, 179:3500–3508.

    CAS  Google Scholar 

  25. Franza T, Michaud-Soret I, Piquerel P, Expert D. (2002) Coupling of iron assimilation and pectinolysis in Erwinia chrysanthemi 3937. Mol Plant-Microbe Interact, 15(11): 1181–1191.

    Article  CAS  Google Scholar 

  26. Nasser W, Reverchon S. (2002) H-NS-dependent activation of pectate lyases synthesis in the phytopathogenic bacterium Erwinia chrysanthemi is mediated by the PecT repressor. Mol Microbiol, 43:733–748.

    CAS  Google Scholar 

  27. Nasser W, Reverchon S, Vedel R, Bocarra M. (2005) PecS and PecT coregulate the synthesis of HrpN and pectate lyases, two virulence determinants in Erwinia Chrysanthemi. Mol Plant-Microbe Interact, 18:1205–1214.

    Article  CAS  Google Scholar 

  28. Lautier T, Nasser W. (2007) The DNA nucleoid-associated protein Fis coordinates the expression of the main virulence genes in the phytopathogenic bacterium Erwinia chrysanthemi. Mol Microbiol, 66:1474–1490.

    CAS  Google Scholar 

  29. Lautier T, Blot N, Muskhelishvili G, Nasser W. (2007) Integration of two essential virulence modulating signals at the Erwinia chrysanthemi pel gene promoters: a role for Fis in the growth-phase regulation. Mol Microbiol, 66:1491–1505.

    CAS  Google Scholar 

  30. Kepseu WD, Woafo P, Sepulchre JA. (2010) Dynamics of the transition to pathogenicity in Erwinia chrysanthemi. J Biol Syst, 18(1): 1–31.

    Article  Google Scholar 

  31. Kepseu WD, Sepulchre JA, Reverchon S, Nasser W. (2010) Towards a quantitative modeling of the synthesis of the pectates lyases, essential virulence factors in Dickeya dadantii. J Biol Chem, 285(37):28565–28676.

    Google Scholar 

  32. Waters CM, Bassler BL. (2005) Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev, 21:319–346.

    CAS  Google Scholar 

  33. Mole BM, Baltrus DA, Dangl JL, Grant SR. (2007) Global virulence regulation networks in phytopathogenic bacteria. Trends Microbiol, 15(8):363–371.

    CAS  Google Scholar 

  34. Nasser W, Reverchon S. (2007) New insights into the regulatory mechanisms of the LuxR family of quorum sensing regulators. Anal Bioanal Chem, 387:381–390.

    CAS  Google Scholar 

  35. Denny TP. (1995) Involvement of bacterial polysaccharides in plant pathogenesis. Annu Rev Phytopathol, 33:173–197.

    Article  CAS  Google Scholar 

  36. Denny TP. (1999) Autoregulator-dependent control of extracellular polysaccharide production in phytopathogenic bacteria. Eur J Plant Pathol, 105:417–430.

    Article  CAS  Google Scholar 

  37. Dockery JD, Keener JP. (2001) A mathematical model for quorum sensing in Pseudomonas aeruginosa. Bull Math Biol, 63:95–11.

    CAS  Google Scholar 

  38. Viretta AU, Fussenegger M. (2004) Modeling the quorum sensing regulatory network of human–pathogenic Pseudomonas aeruginosa. Biotechnol Prog, 20:670–678.

    CAS  Google Scholar 

  39. Von Bodman SB, Bauer WD, Coplin DL. (2003) Quorum sensing in plant pathogenic bacteria. Annu Rev Phytopathol, 41:455–482.

    Article  Google Scholar 

  40. Cabrol S, Olliver A, Pier GB, Andremont A, Ruimy R. (2003) Transcription of quorum-sensing system genes in clinical and environmental isolates of Pseudomonas aeruginosa. J Bacteriol, 185:7222–7230.

    CAS  Google Scholar 

  41. Williams JW, Cui X, Levchenko A, Stevens AM. (2008) Robust and sensitive control of a quorum-sensing circuit by two interlocked feedback loops. Mol Syst Biol, 4:234–245.

    Google Scholar 

  42. Zhu J, Miller MB, Vance RE, Dziejman M, Bassler BL, Mekalanos JJ. (2002) Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. PNAS, 99(5): 3129–3134.

    CAS  Google Scholar 

  43. Francis MS, Wolf-Watz H, Forsberg A. (2002) Regulation of type III secretion systems. Curr Opin Microbiol, 5:166–172.

    CAS  Google Scholar 

  44. Tang X, Xiao Y, Zhou JM. (2006) Regulation of the type III secretion system in phytopathogenic bacteria. Mol Plant-Microbe Interact, 19:1159–1166.

    Article  CAS  Google Scholar 

  45. Brutinel ED, Yahr TL. (2008) Control of gene expression by type III secretory activity. Curr Opin Microbiol, 11:128–133.

    CAS  Google Scholar 

  46. Temme K, Salis H, Tullman-Ercek D, Levskaya A, Hong SH, Voigt CA. (2008) Induction and relaxation dynamics of the regulatory network controlling the Type III secretion system encoded within Salmonella pathogenicity island 1. J Mol Biol, 377:47–61.

    Article  CAS  Google Scholar 

  47. Clark MA, Jepson MA, Simmons NL, Hirst BM. (1994) Preferential interaction of Salmonella typhimurium with mouse Peyer’s patch M cells. Res Microbiol, 145:543–552.

    CAS  Google Scholar 

  48. Jones BD, Ghori N, Falkow S. (1994) Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of Peyer’s patches. J Exp Med, 180:15–23.

    Article  CAS  Google Scholar 

  49. Eriksson S, Lucchini S, Thompson A, Rhen M, Hinton JCD. (2003) Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica. Mol Microbiol, 47:103–118.

    CAS  Google Scholar 

  50. Bajaj V, Lucas RL, Hwang C, Lee CA. (1996) Coordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression. Mol Microbiol, 22:703–714.

    CAS  Google Scholar 

  51. Boddicker JD, Knosp BM, Jones BR. (2003) Transcription of the Salmonella invasion gene activator, hilA, requires HilD activation in the absence of negative regulators. J Bacteriol, 185:525–533.

    Article  CAS  Google Scholar 

  52. Lucas RL, Lee CA. (2001) role of HilC and HilD in regulation of hilA expression in Salmonella enterica sevorar typhimurium. J Bacteriol, 183:2733–2745.

    Article  CAS  Google Scholar 

  53. Boddicker JD, Jones BR. (2004) Long protease activity causes down regulation of Salmonella pathogenicity island I invasion gene expression after infection of epithelial cells. Infect Immun, 72:2002–2013.

    CAS  Google Scholar 

  54. Olekhnovich IN, Kadner RJ. (2002) DNA-binding activities of the HilC and HilD virulence regulatory proteins of Salmonella enterica sevorar typhimurium. J Bacteriol, 184:4148–4160.

    Article  CAS  Google Scholar 

  55. Darwin KH, Miller VL. (2001) Type III secretion chaperone-dependent regulation: activation of virulence genes by SicA and InvF in Salmonella typhimurium. EMBO J, 20:1850–1862.

    CAS  Google Scholar 

  56. Gouzé JL. (1998) Positive and negative circuits in dynamical systems. J Biol Systems, 6:11–15.

    Article  Google Scholar 

  57. Soulé C. (2003) Graphic requirements for multistationnarity. ComplexUs, 1:123–133.

    Article  Google Scholar 

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Acknowledgments

This work was supported by the ANR program “Regupath” (N°ANR-07-BLAN-0212) which is financed by the French Ministry of Research. In particular, W.K. has a post-doctoral contract funded by this ANR. Axel Cournac is acknowledged for stimulating discussions about the bistability in Pel regulation.

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Authors and Affiliations

  1. Institut Non Linéaire de Nice, CNRS UMR 6618, Université de Nice Sophia Antipolis, Valbonne, France

    Wilfred D. Kepseu & Jacques-Alexandre Sepulchre

  2. Laboratoire Interactions Plantes Pathogènes, UMR 217 INRA/AgroParisTech/UPMC Univ Paris 06, Paris, France

    Frédérique Van Gijsegem

Authors
  1. Wilfred D. Kepseu
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  2. Frédérique Van Gijsegem
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  3. Jacques-Alexandre Sepulchre
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Corresponding author

Correspondence to Jacques-Alexandre Sepulchre .

Editor information

Editors and Affiliations

  1. Labo. Bioinformatique des, Génomes et des Réseaux (BiGRe), Université Libre de Bruxelles, bd. du Triomphe, Bruxelles, 1050, Belgium

    Jacques van Helden

  2. Labo. Bioinformatique des, Génomes et des Réseaux (BiGRe), Université Libre de Bruxelles, Bvd. du Triomphe, Bruxelles, 1050, Belgium

    Ariane Toussaint

  3. INSERM 1024, Institut de Biologie de l'Ecole Normale, rue d'Ulm 46, Paris, 75230, France

    Denis Thieffry

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Kepseu, W.D., Van Gijsegem, F., Sepulchre, JA. (2012). Modelling the Onset of Virulence in Pathogenic Bacteria. In: van Helden, J., Toussaint, A., Thieffry, D. (eds) Bacterial Molecular Networks. Methods in Molecular Biology, vol 804. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-361-5_25

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  • DOI: https://doi.org/10.1007/978-1-61779-361-5_25

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-61779-360-8

  • Online ISBN: 978-1-61779-361-5

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