A model of the complex response of Staphylococcus aureus to methicillin

Journal of Theoretical Biology
E PienaarNicolaas F J van Rensburg

Abstract

It is widely accepted that beta-lactam antimicrobials cause cell death through a mechanism that interferes with cell wall synthesis. Later studies have also revealed that beta-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. Solu...Continue Reading

References

Apr 1, 1994·Antimicrobial Agents and Chemotherapy·C RyffelB Berger-Bächi
Jan 1, 1997·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·G A Ayliffe
Jul 7, 2000·The Journal of Infectious Diseases·B ShopsinB N Kreiswirth
Oct 19, 2001·Biochemical and Biophysical Research Communications·K MorikawaT Ohta
Jan 9, 2003·Journal of Clinical Microbiology·Longzhu CuiKeiichi Hiramatsu
Jul 17, 2004·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Christina Scheel ZinnUNKNOWN Sarisa Study Group
May 18, 2005·The Journal of Infectious Diseases·Lucia Grandière-PérezJocelyne Caillon
Oct 1, 2005·Journal of Mathematical Biology·Michael Nikolaou, Vincent H Tam
Feb 1, 2006·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·P C Appelbaum
Dec 7, 2007·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·M FleischhackerM Ruhnke
Jan 16, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Louis B Rice
Feb 9, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Dawn M SievertJeffrey C Hageman

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Citations

Aug 6, 2014·Journal of Theoretical Biology·Yolandy LemmerHendrik Viljoen
Jun 15, 2014·Applied and Environmental Microbiology·Antonio A AlonsoConstantinos Theodoropoulos

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