Deciphering tuberculosis: lysosome-centric insights into pathogenesis and therapies

Tuberculosis is a widely spread disease caused by Mycobacterium tuberculosis (Mtb). The pathogenicity of the pathogen is closely associated with the immune defense mechanisms of the host cells. As key cellular degradation and metabolic centers, lysosomes critically regulate tuberculosis infection. When Mtb invades the host, it is taken up by macrophages and enters phagosomes. Subsequently, the phagosomes fuse with lysosomes and form phagolysosomes, which eliminate the pathogenic bacteria through the acidic environment and hydrolytic enzymes within lysosomes. However, Mtb can interfere with the normal functions of lysosomes through various strategies. It can secrete specific factors (such as ESAT-6, ppk-1, and AcpM) to inhibit the acidification of lysosomes, enzyme activity, and the fusion of phagosomes and lysosomes, thereby enabling Mtb proliferation within host cells. An in-depth exploration of the mechanism of the interaction between Mtb and lysosomes will both uncover bacterial immune evasion strategies and identify novel anti-tuberculosis therapeutic targets.