The gene <i>MAB_2362</i> is responsible for intrinsic resistance to various drugs and virulence in <i>Mycobacterium abscessus</i> by regulating cell division

<i>Mycobacterium abscessus</i> exhibits intrinsic resistance to most antibiotics, hence leading to infections that are difficult to treat. To address this issue, the identification of new molecular targets is essential for the development or repositioning of therapeutic agents. This study demonstrated that the <i>MAB_2362</i>-knockout strain, Mab^Δ2362, became significantly susceptible to a range of antibiotics, not only <i>in vitro</i> but also exhibited susceptibility to rifabutin, bedaquiline, and linezolid <i>in vivo</i>. While the bacterial burden of the wild-type <i>M. abscessus</i> (Mab^Wt) increased by over 1 log₁₀ CFU/lung in a murine infection model 16 days post-infection, that of Mab^Δ2362 strain decreased by more than 1 log₁₀ CFU/lung, which suggests that the disruption leads to attenuation. Bioinformatics analysis revealed that MAB_2362 shares the highest similarity (41.35%) with SteA, a protein known to influence cell division in <i>Corynebacterium glutamicum</i>, suggesting that MAB_2362 might be involved in cell division. Mab^Δ2362 cells exhibited a median length of 2.62 µm, which was substantially longer than the 1.44 µm recorded for Mab^Wt cells. Additionally, multiple cell division septa were observed in 42% of Mab^Δ2362 cells, whereas none were seen in Mab^Wt cells. An ethidium bromide uptake assay further suggested a higher cell envelope permeability in Mab^Δ2362 compared to Mab^Wt. Collectively, these findings underscore the role of <i>MAB_2362</i> in intrinsic resistance and virulence of <i>M. abscessus</i> possibly through the regulation of cell division. Thus, MAB_2362 emerges as a promising candidate for targeted interventions in the pursuit of novel antimicrobials against <i>M. abscessus</i>.