Modeling spatial evolution of multi-drug resistance under drug environmental gradients
Fig 5
An atlas for 2-drug resistance evolution in space under spatial heterogeneity.
We consider only four available mutants each with different resistance phenotypes to two drugs, distributed in the (α, β) space of rescaling parameters: blue—fully resistant to drug 1 and sensitive to drug 2; red—fully resistant to drug 2 and sensitive to drug 1; purple—intermediate resistance to both drugs; brown—wild-type, sensitive to both drugs. We considered a diffusion coefficient of D = 0.01; the spatial equilibrium is obtained numerically by considering the system at t = 400. For all the simulations, we considered the same initial distributions with 99% wild type mutants and the remaining 1% distributed equally among the three resistant mutants. The initial distributions of each mutant were shaped as the function , so that the homogeneous Dirichlet boundary conditions were respected. The growth landscapes were as specified in Eq 16. The interaction strength is fixed at q = 1 both in the case of synergistic and antagonistic interaction. For more drug gradient scenarios, under a more complex drug interaction profile and two diffusion rates, see Supplementary Figs A-C in S1 Text.