Bacterial glyceraldehyde 3-phosphate dehydrogenase (GAPDH)

Bacterial glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a highly conserved enzyme that plays a dual role in bacterial physiology and pathogenesis. Primarily known for its essential role in the glycolytic pathway, it catalyzes the reversible oxidative phosphorylation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, which is critical for ATP production. Beyond its metabolic function, GAPDH acts as a "moonlighting" protein in many pathogenic bacteria, where it is secreted or localized to the cell surface to function as a virulence factor. In this capacity, it facilitates bacterial adhesion to host extracellular matrix proteins, such as plasminogen and fibrinogen, and modulates the host immune response by inducing anti-inflammatory cytokines like IL-10. Because of its essentiality for bacterial survival and its role in host colonization, it is considered a promising target for the development of novel antibiotics and vaccines. However, the high structural similarity between bacterial and human GAPDH isoforms poses a significant challenge for achieving therapeutic selectivity and avoiding potential off-target toxicity.

Other names

G3PDHGapAGapCGapN (Non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase)Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)

Inhibition of glycolytic enzymatic activity leading to ATP depletion and bacterial death; neutralization of extracellular virulence functions to prevent host tissue adhesion and immune evasion.