A computational model of antibiotic-resistance mechanisms in Methicillin-Resistant Staphylococcus aureus (MRSA)

Authored by Marc Devocelle

Date Published: 2008-09-21

DOI: 10.1016/j.jtbi.2008.05.037

Sponsors: Science Foundation Ireland

Platforms: .NET

Model Documentation: Other Narrative

Model Code URLs: Model code not found

Abstract

An agent-based model of bacteria-antibiotic interactions has been developed that incorporates the antibiotic-resistance mechanisms of Methicillin-Resistant Staphylococcus aureus (MRSA). The model, called the Micro-Gen Bacterial Simulator, uses information about the cell biology of bacteria to produce global information about population growth in different environmental conditions. It facilitates a detailed systems-level investigation of the dynamics involved in bacteria-antibiotic interactions and a means to relate this information to traditional high-level proper-ties such as the Minimum Inhibitory Concentration (MIC) of an antibiotic. The two main resistance strategies against beta-lactam antibiotics employed by MRSA were incorporated into the model: beta-lactamase enzymes, which hydrolytically cleave antibiotic molecules, and penicillin-binding proteins (PBP2a) with reduced binding affinities for antibiotics. Initial tests with three common antibiotics (penicillin, ampicillin and cephalothin) indicate that the model can be used to generate quantitatively accurate predictions of MICs for antibiotics against different strains of MRSA from basic cellular and biochemical information. Furthermore, by varying key parameters in the model, the relative impact of different kinetic parameters associated with the two resistance mechanisms to beta-lactam antibiotics on cell survival in the presence of antibiotics was investigated. (C) 2008 Elsevier Ltd. All rights reserved.

Tags

Agent-based model MIC PBP2a bacterial growth beta-lactamase