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Applied and Environmental Microbiology, March 2006, p. 2005-2013, Vol. 72, No. 3
0099-2240/06/$08.00+0     doi:10.1128/AEM.72.3.2005-2013.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Three-Dimensional Computer Model of Four Hypothetical Mechanisms Protecting Biofilms from Antimicrobials

Jason D. Chambless, Stephen M. Hunt, and Philip S. Stewart*

Center for Biofilm Engineering and Department of Chemical and Biological Engineering, Montana State University—Bozeman, Bozeman, Montana 59717-3980

Received 31 August 2005/ Accepted 29 November 2005

Four hypothetical mechanisms for protection of biofilms against antimicrobials were incorporated into a three-dimensional model of biofilm growth and development. The model integrated processes of substrate utilization, diffusion, growth, cell migration, death, and detachment in a cellular automaton framework. Compared to simulations of unprotected biofilms, each of the protective mechanisms provided some tolerance to antimicrobial action. When the mechanisms were compared to each other, the behaviors of the four protective mechanisms produced distinct shapes of killing curves, nonuniform spatial patterns of survival and cell type distribution, and anticipated susceptibility patterns for dispersed biofilm cells. The differences between the protective mechanisms predicted in these simulations could guide the design of experiments to discriminate antimicrobial tolerance mechanisms in biofilms. Each of the mechanisms could be a plausible avenue of biofilm protection.

* Corresponding author. Mailing address: Center for Biofilm Engineering and Department of Chemical and Biological Engineering, Montana State University—Bozeman, Bozeman, MT 59717-3980. Phone: (406) 994-1960. Fax: (406) 994-6098. E-mail: phil_s{at}erc.montana.edu.

Applied and Environmental Microbiology, March 2006, p. 2005-2013, Vol. 72, No. 3
0099-2240/06/$08.00+0     doi:10.1128/AEM.72.3.2005-2013.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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