F Oct. 29

Kimberly Spotts, Department of Microbiology, ASU


Title : A Mathematical Model of the Capsule Biosynthesis Pathway in
Escherichia coli


	The colanic acid biosynthesis pathway in Escherichia coli is of
both scientific and medical importance because it may be responsible for
many antibiotic resistant infections due to biofilm formation. However, it
is often difficult to experimentally demonstrate the mechanisms of the
regulation of this system, so a mathematical model was developed which can
be compared to experimental data obtained in the laboratory. Using the Law
of Mass Action a large system of differential equations was formulated to
describe in detail a particular biochemical system. Also, several
experiments were completed in order to calibrate the rate constants and
several of the parameters from the model. The simulations provide insight
into how the capsular polysaccharide synthesis (cps) operon in E. coli is
affected by several regulatory molecules in the pathway. The model
captures the dynamics of capsule biosynthesis and generates data
concerning the kinetics of capsule expression. The output from these
equations has successfully been compared to experimental data previously
collected on the system.  The simulations provide insight into the
kinetics underlying the two-component regulatory system which controls
expression of the cps operon. It is expected that in the future the model
may provide the basis for new experimentation on the pathway. This
computational study has made it possible to start formulating new
hypotheses about biochemical interactions, previously difficult to
conceptualize.  The model can be applied to the dynamical study of
antibiotic resistant infections and perhaps aid in the design of
experimental protocols to combat these infections. The ultimate goal is to
develop cures for antibiotic resistant infections.

(joint work with Steve Baer and  Valerie Stout)