The many roads to resistance Antibiotic resistance arising from mutation is common among pathogenic bacteria. However, this process is not well understood, and most of the mutations that have been identified to confer resistance do so by modification of the intracellular target or enzymes that can disable the antibacterial compound within the cell. Screening for the evolution of resistance at different temperatures, Lopatkin et al. found that mutations that affect microbial metabolism can result in antibiotic resistance (see the Perspective by Zampieri). These mutations targeted central carbon and energy metabolism and revealed novel resistance mutations in core metabolic genes, expanding the known means by which pathogenic microbes can evolve resistance. Science , this issue p. eaba0862 ; see also p. 783