Oxidative DNA damage is important to the evolution of antibiotic resistance: evidence of mutation bias and its medicinal implications

Abstract Several 1 1These authors contributed equally to this work. Communicated by Ramaswamy H. Sarma studies have revealed that the reactive oxygen species (ROS) induced by antibacterial stimulation accelerates the evolution of antibiotic resistance, which uncovered new links between oxygen rise and evolution and inspired new strategies to prevent antibiotic resistance. Considering many other mechanisms cause DNA mutations aside from ROS damage, evaluating the significance of oxidative DNA damage in the development of antibiotic resistance is of great interest. In this study, we examined the ratio of G:C > T:A transversion to G:C > A:T transition in drug-resistant Escherichia coli and Mycobacterium tuberculosis and found that it is significantly higher than the background values. This finding strongly suggests that ROS damage plays a critical role in the development of antibacterial resistance. Considering the long-term co-evolution between host organisms and pathogenic bacteria, we speculate that the hosts may have evolved strategies for combating antibiotic resistance by controlling DNA damage in bacteria. Analysis of the global transcriptional profiles of Staphylococcus aureus treated with berberine (derived from Berberis, a traditional antibacterial medicine) revealed that the transcription of DNA repair enzymes was markedly upregulated, whereas the antioxidant enzymes were significantly downregulated. Thus, we propose that consolidating the DNA repair systems of bacteria may be a viable strategy for preventing antibiotic resistance. Keywords: reactive oxygen speciesDNA damageantibiotic resistanceevolution Acknowledgments The study was supported by the National Basic Research Program of China (Grant 2010CB126100), the National Natural Science Foundation of China (Grant 21173092) and the Fundamental Research Funds for the Central Universities (Grants 2011PY142 and 2011PY027).