A macroevolution-inspired approach to reveal novel antibiotic resistance mechanisms

With the continuous rise in antibiotic resistance, novel methods that can reveal currently unknown antibiotic resistance mechanisms are essential to prepare and inform health responses. Here we built a library of species representative of the genus Mycobacterium and determined their antibiotic resistance profiles, allowing systematic multispecies comparisons. Analyzing antibiotic resistance in the context of other closely related organisms revealed species with truly exceptional traits, thus providing a solid starting point for the exploration of novel determinants of antibiotic resistance. We illustrate the utility of this genus-level approach to discovery of novel traits by characterizing a previously unrecognized rifamycin-inactivating enzyme that is present in a wide range of bacterial genera.