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Modeling fimbriae mediated parasite-host interactions

Dominique Chu1, David J Barnes

  • 1School of Computing, University of Kent, CT2 7NF Canterbury, UK. D.F.Chu@kent.ac.uk

Journal of Theoretical Biology
|April 3, 2010
PubMed

Insights

This study models the role of type 1 fimbriae in E. coli. Mathematical models suggest fimbriae activate host defenses significantly, and sialic acid

Area of Science:

  • Microbiology
  • Immunology
  • Computational Biology

Background:

  • Type 1 fimbriae are virulence factors in pathogenic Enterobacteriaceae.
  • Commensal E. coli also express fimbriae, potentially to obtain sialic acid.
  • Sialic acid is hypothesized to down-regulate fimbriation to modulate host response.

Purpose of the Study:

  • To assess the plausibility of the hypothesis that commensal fimbriae evoke a mild immune response for nutrient acquisition.
  • To investigate the role of sialic acid in regulating fimbriation and host defense activation.

Main Methods:

  • Development and analysis of mathematical models.
  • Simulation of host-pathogen interactions involving type 1 fimbriae.
  • Parameter sensitivity analysis to explore model robustness.

Main Results:

  • A mild host immune activation by fimbriae is only possible under finely tuned parameters.
  • Under broad conditions, fimbriae activate host defenses to at least 50% of their potential.
  • Sialic acid's suppression of fimbriation appears inconsequential to the overall model dynamics.

Conclusions:

  • The hypothesis of a mild immune response for nutrient acquisition is not robustly supported by the models.
  • Fimbriae-mediated host defense activation is generally substantial, not mild.
  • The regulatory role of sialic acid on fimbriation does not significantly alter the qualitative outcomes of host-pathogen interaction models.

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