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

Edward D Chan,Brendan Podell,Adela Cota-Gomez

doi:10.1128/mbio.03577-20

Abstract

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.

Highlights

Skin and soft tissue infections with or without extension into the joints or bones are most often due to (i) accidental trauma followed by contamination of the wound with environmental Nontuberculous mycobacteria (NTM) or (ii) iatrogenic infections secondary to medical or surgical procedures using NTM-contaminated water, medications, or medical/surgical instruments
A patient with congenital contractural arachnodactyly, a genetic disorder due to FIBRILLIN-2 gene mutation and which shares many clinical features with Marfan syndrome was reported with NTM-LD [36]
MICA is a membrane-bound glycoprotein expressed on various cell types, including alveolar macrophages, epithelioid cells, multinucleated giant cells, intestinal epithelium, and bronchial epithelium, and engages the NKG2D receptor on NK cells, g-d T cells, and CD81 T cells

Summary

Introduction

Skin and soft tissue infections with or without extension into the joints or bones are most often due to (i) accidental trauma followed by contamination of the wound with environmental NTM or (ii) iatrogenic infections secondary to medical or surgical procedures using NTM-contaminated water, medications, or medical/surgical instruments. The A6 allele is a marker for high MICA expression on inflammatory cells and may be involved with increased tissue damage in NTM infections. Following MAC infection, the Nrf2–/– mice had decreased expression of natural resistance-associated macrophage protein 1 (Nramp1) in the lungs as well as in their alveolar macrophages, decreased phagosome-lysosome (P-L) fusion, and increased NTM burden (Fig. 1).

Results

Conclusion