NapR, a novel nucleoid-associated protein, regulates antioxidant defense in mycobacteria

Nucleoid-associated proteins (NAPs) are essential in bacteria for maintaining nucleoid architecture and regulating the expression of target genes. Although some NAPs have been well studied in certain bacterial species, their specific functions and regulatory mechanisms remain poorly characterized in mycobacteria. In this study, we identified NapR as a novel nucleoid-associated protein in mycobacteria. We showed that NapR, which is highly conserved among mycobacteria, binds DNA and modulates DNA topology through bridging. Furthermore, we demonstrated that NapR acts as a positive transcriptional regulator of the <i>ggr</i> gene, which encodes geranylgeranyl reductase, thus regulating bacterial antioxidant defense. By controlling <i>ggr</i> expression, NapR modulates the level of intracellular ROS and influences the antioxidant capacity of mycobacteria. This study identifies NapR as a novel nucleoid-associated protein and defines a specific regulatory pathway involved in mycobacterial antioxidant defense, providing new insights into the mechanisms of the bacterial oxidative stress response.IMPORTANCEAs important global regulatory factors, nucleoid-associated proteins (NAPs) can help bacteria adapt to environmental stress, such as oxidative stress. However, the regulatory mechanism of NAPs in mycobacterial antioxidant defense is largely unclear and remains to be explored. Here, we identify NapR as a novel nucleoid-associated protein that modulates DNA topology by bridging. We revealed the regulatory effect of NapR on mycobacterial antioxidant defense. NapR positively regulates the expression of the geranylgeranyl reductase-encoding gene <i>ggr</i>. In addition, the ability of NapR to regulate the levels of intracellular ROS relies on <i>ggr</i>, ultimately leading to the antioxidant defense of <i>Mycobacterium smegmatis</i>. Our findings identify a new member of the NAP family and contribute to understanding the mechanisms of bacterial antioxidant defense.