A 3D computer model investigation of biofilm detachment and protection mechanisms
Chambless, Jason Daniel.
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A biofilm is a dense aggregation of microorganisms attached to each other and a supporting surface. Biofilms are ubiquitous in industrial environments and are also frequently recognized as the source of persistent infections. Biofilm invasions and biofilm-induced infections are often difficult or impossible to remedy. This dissertation presents the results of a 3D hybrid computer model, BacLAB, which was used to simulate detachment and protection mechanisms of biofilms in a cellular automata framework. Protection against antimicrobials afforded by each of four hypothesized protective mechanisms was investigated in order to examine population survival versus antimicrobial exposure time, and the spatial patterns of chemical species and cell types. When compared to each other, the behaviors of the slow penetration, adaptive stress response, substrate limitation, and persister mechanisms produced distinct shapes of killing curves, non-uniform spatial patterns of survival and cell type distribution, and anticipated susceptibility patterns of dispersed biofilm cells.Detachment is an important process that allows an organism the possibility of traveling to and colonizing a new location. Detachment also balances growth and so determines the net accumulation of biomass on the surface. Three hypothetical mechanisms representing various physical and biological influences of detachment were incorporated into BacLAB. The purpose of this investigation was to characterize each of the mechanisms with respect to four criteria: the resulting biofilm structure, the existence of a steady state, the propensity for sloughing events, and the dynamics during starvation. The results showed that varying the detachment mechanism is a critical determinant of biofilm structure and of the dynamics of biofilm accumulation and loss. Phenotypic variants, in the form of dormant cells, can often survive an antimicrobial treatment. The existence of these cells, termed persisters, is one hypothetical explanation for biofilm recalcitrance. Four different combinations of random and substrate-dependant persister mechanisms were simulated through the use of the BacLAB model. The purpose of this study was to determine and compare the effects of differing formation and resuscitation strategies on persister-related protection of biofilms. Analysis of the simulations showed that extended periods of dormancy, without regard to the mechanism, were directly responsible for more tolerant biofilms.