Price equation captures the role of drug interactions and collateral effects in the evolution of multidrug resistance.

ABSTRACT: Bacterial adaptation to antibiotic combinations depends on the joint inhibitory effects of the two drugs (drug interaction [DI]) and how resistance to one drug impacts resistance to the other (collateral effects [CE]). Here we model these evolutionary dynamics on two-dimensional phenotype spaces that leverage scaling relations between the drug-response surfaces of drug-sensitive (ancestral) and drug-resistant (mutant) populations. We show that evolved resistance to the component drugs - and in turn, the adaptation of growth rate - is governed by a Price equation whose covariance terms encode geometric features of both the two-drug-response surface (DI) in ancestral cells and the correlations between resistance levels to those drugs (CE). Within this framework, mean evolutionary trajectorie

SUBMITTER: Gjini E 

PROVIDER: S-EPMC8331190 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature