Joseph R. Peterson, John A. Cole, and Zaida Luthey-Schulten.
Parametric studies of metabolic cooperativity in escherichia coli
colonies: Strain and geometric confinement effects.
PLoS One, 12:e0182570, 2017.
(PMC: PMC5562313)
PETE2017-ZLS
Characterizing the complex spatial and temporal interactions among cells
in a biological system (i.e. bacterial colony, microbiome, tissue, etc.)
remains a challenge. Metabolic cooperativity in these systems can arise
due to the subtle interplay between microenvironmental conditions and the
cells’ regulatory machinery, often involving cascades of intra- and
extracellular signalling molecules. In the simplest of cases, as
demonstrated in a recent study of the model organism Escherichia coli,
metabolic cross-feeding can arise in monoclonal colonies of bacteria driven
merely by spatial heterogeneity in the availability of growth substrates;
namely, acetate, glucose and oxygen. Another recent study demonstrated
that even closely related E. coli strains evolved different glucose utilization
and acetate production capabilities, hinting at the possibility of subtle
differences in metabolic cooperativity and the resulting growth behavior of
these organisms. Taking a first step towards understanding the complex
spatio-temporal interactions within microbial populations, we performed a
parametric study of E. coli growth on an agar substrate and probed the
dependence of colony behavior on: 1) strain-specific metabolic
characteristics, and 2) the geometry of the underlying substrate. To do so,
we employed a recently developed multiscale technique named 3D
dynamic flux balance analysis which couples reaction-diffusion simulations
with iterative steady-state metabolic modeling. Key measures examined
include colony growth rate and shape (height vs. width), metabolite
production/consumption and concentration profiles, and the emergence of
metabolic cooperativity and the fractions of cell phenotypes. Five closely
related strains of E. coli, which exhibit large variation in glucose
consumption and organic acid production potential, were studied. The
onset of metabolic cooperativity was found to vary substantially between
these five strains by up to 10 hours and the relative fraction of acetate
utilizing cells within the colonies varied by a factor of two. Additionally,
growth with six different geometries designed to mimic those that might be
found in a laboratory, a microfluidic device, and inside a living organism
were considered. Geometries were found to have complex, often nonlinear
effects on colony growth and cross-feeding with “hard” features resulting
in larger effect than “soft” features. These results demonstrate that strain-
specific features and spatial constraints imposed by the growth substrate
can have significant effects even for microbial populations as simple as
isogenic E. coli colonies.
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