Cutibacterium acnes glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

Cutibacterium acnes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme essential for the survival and pathogenicity of the Gram-positive bacterium C. acnes, the primary organism associated with acne vulgaris. In its canonical metabolic role, GAPDH catalyzes the sixth step of glycolysis, converting glyceraldehyde-3-phosphate into 1,3-bisphosphoglycerate, which is vital for bacterial energy production. Beyond metabolism, C. acnes GAPDH functions as a moonlighting protein that is secreted or localized to the bacterial cell surface, where it facilitates adhesion to host tissues and binds to human plasminogen, aiding in colonization and immune evasion. Because of its dual role in essential metabolism and virulence, it is considered a promising target for the development of novel antibacterial agents and vaccines, particularly to address the rising challenge of antibiotic-resistant C. acnes strains. However, the high degree of structural similarity between bacterial and human GAPDH presents a significant therapeutic challenge, requiring the design of highly selective inhibitors to avoid systemic metabolic interference in the host. Currently, while GAPDH is widely used as a housekeeping control in molecular studies of C. acnes, there are no FDA-approved drugs that specifically target this enzyme.

Other names

Glyceraldehyde-3-phosphate dehydrogenaseG3PDGAPDG3PDHGlyceraldehyde-3-phosphate dehydrogenase (phosphorylating)

Inhibition of glycolytic activity to disrupt bacterial energy metabolism and interference with surface-associated moonlighting functions to prevent bacterial adhesion and host colonization.