A model of the complex response of Staphylococcus aureus to methicillin

Elsje Pienaar, Scott E. Whitney, Hendrik J Viljoen, Nicolaas F J van Rensburg

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

It is widely accepted that β-lactam antimicrobials cause cell death through a mechanism that interferes with cell wall synthesis. Later studies have also revealed that β-lactams modify the autolysis function (the natural process of self-exfoliation of the cell wall) of cells. The dynamic equilibrium between growth and autolysis is perturbed by the presence of the antimicrobial. Studies with Staphylococcus aureus to determine the minimum inhibitory concentration (MIC) have revealed complex responses to methicillin exposure. The organism exhibits four qualitatively different responses: homogeneous sensitivity, homogeneous resistance, heterogeneous resistance and the so-called 'Eagle-effect'. A mathematical model is presented that links antimicrobial action on the molecular level with the overall response of the cell population to antimicrobial exposure. The cell population is modeled as a probability density function F(x,t) that depends on cell wall thickness x and time t. The function F(x,t) is the solution to a Fokker-Planck equation. The fixed point solutions are perturbed by the antimicrobial load and the advection of F(x,t) depends on the rates of cell wall synthesis, autolysis and the antimicrobial concentration. Solutions of the Fokker-Planck model are presented for all four qualitative responses of S. aureus to methicillin exposure.

Original languageEnglish (US)
Pages (from-to)438-445
Number of pages8
JournalJournal of Theoretical Biology
Volume257
Issue number3
DOIs
Publication statusPublished - Apr 7 2009

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Keywords

  • Cell wall
  • Eagle-effect
  • Fokker-Planck equation
  • Heterogeneous resistance
  • Mathematical model
  • Methicillin
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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