Chaperonin GroEL 1 (Cpn60.1) (Cpn60.1)

Chaperonin Cpn60.1, also known as GroEL1, is a molecular chaperone in Mycobacterium tuberculosis (Mtb) that belongs to the Group I chaperonin family. While its homolog Cpn60.2 (GroEL2) is essential for growth, Cpn60.1 is dispensable under normal conditions but critical for Mtb virulence and survival during stress, such as hypoxia and copper toxicity. It is specifically involved in the biosynthesis of phthiocerol dimycocerosates (PDIM) and phenolic glycolipids (PGL), which are essential cell wall lipids that contribute to the bacteria's impermeability and intrinsic resistance to antibiotics like rifampicin and vancomycin. Beyond its role in protein folding and cell wall maintenance, Cpn60.1 acts as a potent moonlighting protein that is released into the extracellular space, where it stimulates the production of proinflammatory cytokines in host macrophages and regulates granuloma formation. Experimental studies have identified small molecule inhibitors and peptides derived from Cpn60.1 that can modulate these inflammatory responses or enhance the efficacy of existing anti-tuberculosis drugs. Consequently, Cpn60.1 is considered a promising therapeutic target for both direct antimicrobial action and host-directed therapy in tuberculosis.

Other names

GroEL1Hsp60-160 kDa chaperonin 1Chaperonin-60 1Rv3417c

Inhibition of Cpn60.1 disrupts the biosynthesis of phthiocerol dimycocerosates (PDIM) and phenolic glycolipids (PGL), leading to compromised cell wall integrity and increased susceptibility to antibiotics. It also impairs biofilm formation and copper tolerance.