Chemogenomic model identifies synergistic drug combinations robust to the pathogen microenvironment.

ABSTRACT: Antibiotics need to be effective in diverse environments in vivo. However, the pathogen microenvironment can have a significant impact on antibiotic potency. Further, antibiotics are increasingly used in combinations to combat resistance, yet, the effect of microenvironments on drug-combination efficacy is unknown. To exhaustively explore the impact of diverse microenvironments on drug-combinations, here we develop a computational framework-Metabolism And GENomics-based Tailoring of Antibiotic regimens (MAGENTA). MAGENTA uses chemogenomic profiles of individual drugs and metabolic perturbations to predict synergistic or antagonistic drug-interactions in different microenvironments. We uncovered antibiotic combinations with robust synergy across nine distinct environments against both E. co

SUBMITTER: Cokol M 

PROVIDER: S-EPMC6329523 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature