CysK2 couples copper sensing to redox adaptation in Mycobacterium tuberculosis.

CysK2 links copper sensing to redox homeostasis, enabling Mycobacterium tuberculosis to persist during infection, with cysK2-deficient mutants showing reduced long-term survival in mice.

• Why it matters: Understanding how M. tuberculosis adapts to host-imposed copper exposure is crucial because it influences bacterial survival and pathogenicity within host cells, yet the physiological mechanisms remain unclear.
• What they did: The study used high-resolution imaging, transcriptomic profiling, intracellular reporter assays, and mouse infection models to investigate copper responses, revealing that copper reaches intracellular bacteria and induces a specific transcriptional response, notably upregulating cysK2.
• The result: CysK2 was identified as a copper-responsive effector that links copper sensing to sulfur metabolism and redox balance, and its absence reduces bacterial persistence and shifts redox potential, highlighting its role in long-term infection survival.