Modeling spatial evolution of multi-drug resistance under drug environmental gradients
Fig 7
Selection outcomes for periodic drug regimes leading to periodic growth rates over space.
A. The periodic variation of drug 1 and drug 2 over space, keeping the total amount of each drug equal. The periodic function parameters, under conservation of total drug, are: k1 = A1 = 0.5, T1 = 2 and k2 = A2 = 0.72, T2 = 0.4. Further we show mutant growth rates and selection outcome following the linear G function combinations in Eq 16 under: B. synergistic drug interactions (strength q = 0.5); C. independent drugs; D. antagonistic drug interactions (strength q = 0.5); E. even more antagonistic drugs (strength q = 1.5). The first column shows resulting growth rates gi(z) for each mutant. The second column shows associated principal eigenvalues for each of the 3 mutants over space, computed as an indicator of overall fitness where D1 refers to the mutant resistant to drug 1, D2 the mutant resistant to drug 2 and Double, the mutant partially resistant to both drugs. Assumed diffusion coefficient is D = 0.01. (See also S4 Mathematica Notebook for this case).