Bacterial sorbitol-6-phosphate dehydrogenase and sorbitol-specific phosphotransferase system (S6PDH/Sor-PTS)

Bacterial sorbitol-6-phosphate dehydrogenase and sorbitol-specific transporters constitute a specialized metabolic pathway used by various bacteria, including the dental pathogen Streptococcus mutans and enteric bacteria like Escherichia coli, to utilize sorbitol as a carbon source (UniProt P0A9S1). The transport system, usually a component of the phosphoenolpyruvate-dependent phosphotransferase system (PTS), facilitates the import of sorbitol while simultaneously phosphorylating it to sorbitol-6-phosphate (PubMed 25651384). Subsequently, sorbitol-6-phosphate dehydrogenase (EC 1.1.1.140) catalyzes the NAD+-dependent oxidation of this intermediate into fructose-6-phosphate, which enters the glycolytic pathway to produce energy and organic acids (KEGG entry C00191). This system is a primary target for anti-caries agents like xylitol, which acts as a decoy substrate; it is transported and phosphorylated by the PTS but cannot be further metabolized by the dehydrogenase, resulting in the toxic accumulation of xylitol-5-phosphate and the inhibition of bacterial growth (PubMed 1695368). Targeting these proteins offers a strategy to modulate the oral and gut microbiome by selectively inhibiting bacteria that rely on these pathways for competitive survival.

Other names

D-sorbitol-6-phosphate dehydrogenaseSrlDGutBSorbitol-specific EII componentGlucitol-specific phosphotransferase systemSorbitol-6-phosphate 2-dehydrogenase

Competitive inhibition of sorbitol uptake and induction of a futile metabolic cycle through the accumulation of non-metabolizable sugar phosphates, leading to ATP depletion and growth inhibition.