The complex response of Staphylococcus aureus to methicillin

Elsje Pienaar, Scott E. Whitney, Hendrik J. Viljoen

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Staphylococcus aureus exhibits complex responses to β-lactam antibiotics. A model is presented that describes these complex responses. The cell wall thickness of the organism varies naturally as a result of small variations in the key processes that determine its dynamic equilibrium: the synthesis rate of peptidoglycans and autolysis rates of cell walls. The β-lactams are designed to interrupt the synthesis of cell wall by penicillin binding proteins (PBP), thence thinning of the cell wall and eventual cell death occurs due to turgor. But the lactams also affect the activity of the autolysin, and drug-resistant strains have the capability to shift the synthesis to alternative, oftentimes over-expressed, PBP and thicker than normal cell walls can form. 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 modified Fokker-Planck equation: Ft= DFxx -(FV)x+G(F,x) -R(F,x). The 'velocity' V is the difference between synthesis and autolysis rates which depend on the antibiotic concentration. The roots of V denote dynamic equilibrium, but not all roots are stable fixed points of the Fokker-Planck equation. Results are presented which qualitatively agree with experimental MIC studies for the exposure of Staphylococcus aureus to methicillin. The model describes homogeneous sensitive and homogeneous resistant behavior as well as the more complex cases of heterogeneous resistance and the Eagle effect. The latter effect had been observed soon after the introduction of penicillin and it refers to the paradoxical increase in cell population at increased antibiotic concentrations.

Original languageEnglish (US)
Title of host publicationAIChE Annual Meeting, Conference Proceedings
StatePublished - 2009
Event2009 AIChE Annual Meeting, 09AIChE - Nashville, TN
Duration: Nov 8 2009Nov 13 2009

Other

Other2009 AIChE Annual Meeting, 09AIChE
CityNashville, TN
Period11/8/0911/13/09

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

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    Pienaar, E., Whitney, S. E., & Viljoen, H. J. (2009). The complex response of Staphylococcus aureus to methicillin. In AIChE Annual Meeting, Conference Proceedings