Zinc: An Emerging Axis of Host–Pathogen Interaction in Tuberculosis

Zinc is an essential micronutrient required by all forms of life, including Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis. Mtb can persist within the host for years and requires a prolonged, multidrug treatment regimen for effective clearance. The sequestration of essential metals, including zinc, during bacterial infection is a key component of the host’s innate immune response. In this process, metal-chelating proteins such as the neutrophil-derived protein, calprotectin, play a central role in nutritional immunity by limiting microbial access to critical metal cofactors. Despite its importance, the impact of nutritional immunity on Mtb pathogenesis remains incompletely understood. In this review, we summarize recent advances in our understanding of zinc-responsive adaptations in Mtb and propose that zinc limitation within the host contributes significantly to the long-term persistence of this pathogen.