Researchers at Cornell University have discovered a mechanism of activation and inactivation in ribonucleotide reductase (RNR) that potentially offers a new pathway for targeting pathogens in the fight against antibiotic-resistant bacteria.
According to their paper published last week in Nature Communications, understanding the "switch" that can turn RNR off provides a possible means to shut off the reproduction of harmful bacteria. In all organisms, the regulation of RNRs involves complex mechanisms. Without these mechanisms, DNA replication becomes error-prone, and dangerous mutations could occur.
"Without the RNR enzyme, DNA-based life as we know it could not exist," said first author William Thomas. "If we understand the RNR 'off switch' well enough, we can take advantage of it by developing our own ways to toggle it with new antibiotic drug molecules."
This research reveals evolution in action, according to Nozomi Ando, the paper's senior author. The lack of the normal regulatory "switch" mechanism may provide an evolutionary advantage for the bacteria they studied. "Usually the increased chance of mutations is a problem for bacteria, but maybe under certain circumstances it's actually advantageous for an organism to mutate and possibly become resistant to an antibiotic or another stressful situation," she said.
RNRs are not easy proteins to work with or understand, and the researchers said characterizing them in the traditional way has been challenging. "The combination of small-angle X-ray scattering using CHESS [Cornell High Energy Synchotron Source], crystallography, and cryo-electron microscopy is what made this study possible," Ando added.