A multilayered repair system protects the mycobacterial chromosome from endogenous and antibiotic-induced oxidative damage

Significance Oxidative stress is a common insult to all living organisms, in part because of its potent DNA-damaging effects leading to cell death and mutagenesis. In bacteria, antibiotics are one source of oxidative stress. Some DNA repair systems that counteract oxidative-induced mutagenesis have been described inEscherichia coli as participating in antibiotic killing action. However, in mycobacteria, which include agents of tuberculosis and leprosy, roles of these oxidative DNA repair systems are poorly understood because multiple and redundant enzymes are encoded. This study definitively dissects this redundancy using genetic approaches. We uncover an intricate set of DNA repair systems that defend the mycobacterial chromosome against endogenous oxidative mutagenesis. While some of them protect against antibiotic-induced oxidative killing, others participate in it.