Abstract:

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) infection, remains a major global public health challenge. Transition metals can stabilize substrates or reaction intermediates at the active sites of enzymes and are extensively involved in enzymatic catalytic processes. Both bacteria and host cells must precisely regulate the levels of these metal elements to meet physiological needs while avoiding potential toxicity. In recent years, increasing studies have uncovered new mechanisms of microbial direct metal poisoning, which are considered critical components of the host immune system to restrict pathogen survival. Host cells can regulate intracellular concentrations of metal ions, such as zinc, copper, and iron, as an innate immune mechanism to inhibit the growth of intracellular pathogens.In response to these challenges, MTB possesses complex metal detoxification systems. Through metal pumps, chelator, and antioxidant enzymes, MTB can maintain metal homeostasis under host-imposed metal stress and evade immune attacks. These detoxification mechanisms are essential for the pathogen’s survival and persistent infection. This study systematically explores the reprogramming of metal ion metabolism in host cells during MTB infection, providing an in-depth analysis of host cell regulation of various metal ions and their roles in antimicrobial defense. It reveals the dynamic changes in metal ion metabolism and its significance in infection defense. Understanding these metabolic processes aids in elucidating the pathogenesis of tuberculosis, offers new insights into its prevention and treatment, and provides a theoretical foundation for the development of novel anti-tuberculosis therapeutic strategies.

Key words: Mycobacterium tuberculosis, Macrophages, Metal ions, Ceruloplasmin