GDP-mannose 6-dehydrogenase (GMD)

GDP-mannose 6-dehydrogenase (GMD), also known as AlgD, is a critical enzyme in the biosynthesis of alginate, a mucoid exopolysaccharide produced by the bacterium Pseudomonas aeruginosa [1, 4]. It catalyzes the irreversible, NAD+-dependent double oxidation of GDP-D-mannose to GDP-D-mannuronic acid, serving as the rate-limiting step in the alginate biosynthetic pathway [1, 7]. Alginate production is a hallmark of the mucoid phenotype in P. aeruginosa, forming a protective biofilm that shields the bacteria from host immune defenses and significantly reduces the efficacy of antibiotic treatments, particularly in the lungs of cystic fibrosis patients [5, 14]. Because GMD has no direct human homolog, it is an attractive target for the development of anti-virulence and anti-biofilm agents [4, 11]. Experimental inhibitors, such as C6-modified sugar nucleotide analogs and amino-sulfonyl-guanosine derivatives, have shown the ability to inhibit GMD activity and reduce alginate production in vitro [6, 12]. By targeting this enzyme, researchers aim to disrupt biofilm integrity and restore the sensitivity of mucoid bacterial strains to conventional antibiotics like aminoglycosides [11, 15].

Other names

GDP-mannose dehydrogenaseGuanosine diphosphomannose dehydrogenaseGuanosine diphospho-D-mannose dehydrogenaseAlgD

Inhibition of GDP-mannose 6-dehydrogenase activity to block the production of GDP-mannuronic acid, thereby preventing alginate polymerization and disrupting biofilm formation.