Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β- D -arabinose biosynthetic and utilization pathway genes

David Alland and colleagues report sequencing of Mycobacterium tuberculosis strains under ethambutol drug selection. They follow the multistep progression in acquisition of ethambutol resistance in clinical isolates, finding that an interaction of mutations in several genes in DPA biosynthetic and utilization pathways influence the level of resistance as measured by the minimal inhibitory concentration.