Center for Biofilm Engineering
Abstract:
"Modeling Antibiotic Tolerance in Biofilms by Accounting for Nutrient
Limitation"
04-002 A mathematical model of biofilm dynamics was used to
investigate the protection from antibiotic killing that can be afforded to
microorganisms in biofilms based on a mechanism of localized nutrient limitation
and slow growth. The model assumed that the rate of killing by the antibiotic
was directly proportional to the local growth rate. Growth rates in the biofilm
were calculated by using the local concentration of a single growth-limiting
substrate with Monod kinetics. The concentration profile of this metabolic
substrate was calculated by solving a reaction-diffusion problem. The model
predicted the following features: stratified patterns of growth with zones of no
growth in the biofilm interior, slow killing of biofilm microorganisms that was
further retarded as the initial biofilm thickness increased, nonuniform spatial
patterns of killing inside the biofilm, biofilm killing rates that decrease in a
nonlinear way as the concentration of the growth-limiting substrate feeding the
biofilm is decreased, and heightened tolerance when external mass transfer
resistance is manifested. This modeling study also provides motivation for
further investigation of a hypothetical cell state in which damaged cells score
as nonviable but continue to consume substrate. The existence of such a cell
state can further retard biofilm killing, according to the simulations. The
results support the important contributions of nutrient limitation and slow
growth to the antibiotic tolerance of microorganisms in biofilms.
Roberts, M.E. and P.S. Stewart, "Modeling Antibiotic Tolerance in
Biofilms by Accounting for Nutrient Limitation," Antimicrob. Agents Chemother.,48(1):48-52
(2004) |
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