One Drug Multiple Targets: An Approach To Predict Drug Efficacies on Bacterial Strains Differing in Membrane Composition

The development of drug resistance by bacterial adaptation or undesirable damage to gut microbiota raise new challenges in drug design and require one to look beyond the canonical approach of screening multiple drugs against a single target. We develop a complementary approach, one drug multiple targets, and quantitatively illustrate it for a specific case of antibiotic targeting membranes. We curated the data on the activity of daptomycin against Staphylococcus aureus strains with different membrane compositions, varying mainly in lysylation and validated the concept. The results of the predictions are good and, within the limits of the scarcely available data, hint at the activity of daptomycin by interacting with the outer leaflet of the membrane.