Simulating Serial-Target Antibacterial Drug Synergies Using Flux Balance Analysis.

ABSTRACT: Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts cannot predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some of the most widely used antibiotic treatments. Here we extend FBA modeling to simulate responses to chemical inhibitors at varying concentrations, by diverting enzymatic flux to a waste reaction. This flux diversion yields very similar qualitative predictions to prior methods for single target activity. However, we find very different predictions for combinations, where flux diversion, which mimics the kinetics of competitive metabolic inhibitors, can explain serial target synergies between metabolic e

SUBMITTER: Krueger AS 

PROVIDER: S-EPMC4731467 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature