Adding Another Piece to the Puzzle of Why NTM Infections Are Relatively Uncommon despite Their Ubiquitous Nature

Since nontuberculous mycobacteria (NTM) are pervasive in the environment and NTM infections are relatively uncommon, underlying hereditary or acquired host susceptibility factors should be sought for in most NTM-infected patients. To facilitate identification of underlying risk factors, it is useful to classify NTM disease into skin-soft tissue infections, isolated NTM lung disease, and extrapulmonary visceral/disseminated disease because the latter two categories have unique sets of underlying host risk factors. Nakajima and coworkers (M. Nakajima, M. Matsuyama, M. Kawaguchi, T. Kiwamoto, et al., mBio 12:e01947-20, 2021, https://doi.org/10.1128/mBio.01947-20) in a recent issue of mBio found that Nrf2 (nuclear factor erythroid 2-related factor 2), a transcription factor that is induced by oxidative stress but induces antioxidant molecules, provides protection against an NTM infection in a murine model. While they showed that Nrf2 induction of Nramp-1 enhanced phagosome-lysosome fusion, we discuss other potential mechanisms by which oxidative stress predisposes to and Nrf2 protects against NTM infections.