title: Multidrug evolutionary strategies to reverse antibiotic resistance.
abstract: Antibiotic treatment has two conflicting effects: the desired, immediate effect of inhibiting bacterial growth and the undesired, long-term effect of promoting the evolution of resistance. Although these contrasting outcomes seem inextricably linked, recent work has revealed several ways by which antibiotics can be combined to inhibit bacterial growth while, counterintuitively, selecting against resistant mutants. Decoupling treatment efficacy from the risk of resistance can be achieved by exploiting specific interactions between drugs, and the ways in which resistance mutations to a given drug can modulate these interactions or increase the sensitivity of the bacteria to other compounds. Although their practical application requires much further development and validation, and relies on advances in genomic diagnostics, these discoveries suggest novel paradigms that may restrict or even reverse the evolution of resistance.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Baym
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Stone
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Department of Biology and Department of Computer Science, Technion - Israel Institute of Technology, Haifa, Israel. rkishony@technion.ac.il.
authors.forename: Roy
authors.initials: R
authors.lastname: Kishony
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D009154:Mutation; D012641:Selection, Genetic
chemical_list: D000900:Anti-Bacterial Agents