Mycobacterium tuberculosis stimulates cuproptosis by regulating Lnc-Gm5532 to target FDX1 for bacteria intracellular survival.

Cuproptosis is a novel cell death modality but its regulatory role in tuberculosis remains obscure. This study is committed to explore the specific mechanism of cuproptosis induced by Mycobacterium tuberculosis (M.tb) infection. We confirmed that M.tb induced cuproptosis contributes to its intracellular survival. Then microarray analysis was employed to screen M.tb-infected DE mRNAs and LncRNAs which may be potential regulators of cuproptosis. We focus on a key cuproptosis gene FDX1, and 7 LncRNAs that can target FDX1. Among them, LncRNA-Gm5532 upregulated the expression of FDX1 by sponging miR-7232-5p, which further promoted the expression of cuproptosis-associated proteins, increased intracellular copper ions, worsened lipid acylation-DLAT aggregation, and resulting in cuproptosis. Meanwhile, LncRNA-Gm5532 boosts the survival of M.tb in macrophages. Collectively, LncRNA-Gm5532 exacterbates M.tb-induced cuproptosis by targeting FDX1 and promotes immune escape of M.tb. The study will provide new insights into the regulation of tuberculosis pathogenesis.