Randomized trial reveals the role of Rv1983 in inducing macrophage ferroptosis, suggesting a potential tuberculosis treatment target.
Key Points
This study aims to investigate the role of Rv1983 in inducing ferroptosis in macrophages and its implications for Mycobacterium tuberculosis dissemination.
Screened for Mtb RD region-encoded proteins affecting macrophages
Characterized Rv1983-induced macrophage death through cytotoxicity assays and flow cytometry
Constructed an Rv1983-knockout Mtb strain to evaluate its dissemination in infected macrophages.
Rv1983 promotes ferroptosis in macrophages by targeting GPX4 for K48-linked ubiquitination.
H37RaΔRv1983 strain shows reduced Mtb dissemination in both in vitro and in vivo models.
Rv1983 interacts with TRIM25 to facilitate the degradation of GPX4, enhancing macrophage susceptibility to ferroptosis.