Heat shock protein 16.3 (Hsp16.3) (Hsp16.3)

Heat shock protein 16.3 (Hsp16.3), also known as HspX or Acr, is a small heat shock protein (sHSP) produced by Mycobacterium tuberculosis (Mtb) [1, 3]. It belongs to the alpha-crystallin family and functions as a molecular chaperone that prevents the aggregation of denatured proteins under stress conditions [3, 11]. Hsp16.3 is predominantly expressed during the stationary phase and is essential for the long-term survival and dormancy of the pathogen within the host, particularly during latent tuberculosis infection (LTBI) [1, 5]. It contributes to cell wall thickening and helps the bacteria evade host immune responses by inhibiting macrophage autophagy and inducing M2 polarization [1, 8, 32]. Due to its high expression in latent stages and strong immunogenicity, Hsp16.3 is a major target for the development of diagnostic biomarkers, vaccines, and novel therapeutic interventions aimed at eradicating dormant bacilli [4, 6, 21]. Experimental approaches include the use of specific antibodies and peptide inhibitors to disrupt its chaperone function or enhance host clearance of the bacteria [2, 20, 24]. Targeting Hsp16.3 may provide a strategy to shorten tuberculosis treatment regimens and prevent disease reactivation [21, 23].

Other names

HspXAcrAcr116 kDa antigenAlpha-crystallin-related protein 1Rv2031c

Inhibition of chaperone activity to disrupt bacterial dormancy and survival; modulation of host immune response to enhance bacterial clearance; reversal of autophagy inhibition in macrophages.