Heat shock protein X (HspX) (HspX)

Heat shock protein X (HspX), also known as alpha-crystallin (Acr) or the 16 kDa antigen, is a small heat shock protein (sHSP) and molecular chaperone in Mycobacterium tuberculosis [1, 5]. It is encoded by the Rv2031c gene and is a member of the alpha-crystallin family [1, 3]. HspX is one of the most highly upregulated proteins during the stationary phase and under conditions of hypoxia and nitric oxide stress, which are characteristic of the environment within host granulomas during latent tuberculosis infection (LTBI) [2, 7, 9]. Its primary biological function is to act as a chaperone, preventing the irreversible aggregation of denatured proteins, and it also plays a critical role in slowing the growth of the bacterium to facilitate entry into a dormant, non-replicating state [3, 4, 7]. Because of its high expression and immunogenicity during latency, HspX is a major target for the development of "multistage" subunit vaccines designed to prevent both primary infection and reactivation of latent disease [4, 6, 22]. Additionally, HspX serves as a valuable diagnostic biomarker for identifying individuals with LTBI and is being explored as a therapeutic target to shorten the duration of tuberculosis treatment by disrupting the survival mechanisms of persistent bacilli [2, 8, 24]. While no small-molecule inhibitors are currently approved, experimental studies suggest that inhibiting HspX could sensitize dormant bacteria to conventional antibiotics and reduce relapse rates [8, 24].

Other names

Alpha-crystallinAcr16 kDa antigen14 kDa antigenHsp16.3Rv2031cNox16

Immunostimulation (vaccine candidates); Inhibition of chaperone activity (experimental); Disruption of growth regulation (experimental)