The MmpS6-MmpL6 Operon Is an Oxidative Stress Response System Providing Selective Advantage to<i>Mycobacterium tuberculosis</i>in Stress

Abstract

Background: The stress response adaptability of Mycobacterium tuberculosis (Mtb) is still unresolved. In this study, we ascribe an important function to the MmpS6-MmpL6 (M6) operon in Mtb stress management. Methods: By using a novel promoter probe in a high-throughput unbiased screen, we identified several quinones as potent inducers of the M6 operon in addition to triclosan. Results: Triclosan and plumbagin effectively altered the intracellular redox potential in Mtb suggestive of oxidative stress in bacteria. Presence of the functional M6 operon correlated with an enhanced ability of clinical strains to survive in the presence of triclosan. Conclusions: Similar to the addition of a powerful reactive oxygen species-quenching agent such as N-acetyl cysteine in the medium, introduction of the complete M6 operon was sufficient to increase tolerance of the M6- strains to triclosan and plumbagin by effectively ablating the change in intracellular redox potential of Mtb, signifying the importance of this operon in oxidative stress survival in mycobacteria.