Glycerol-3-phosphate transporter (GlpT) (GlpT)

Glycerol-3-phosphate transporter (GlpT) is a bacterial membrane protein belonging to the Major Facilitator Superfamily (MFS) that mediates the exchange of external glycerol-3-phosphate for internal inorganic phosphate. It is primarily found in Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, where it plays a crucial role in nutrient acquisition by allowing the cell to utilize glycerol-3-phosphate as a carbon and phosphorus source. In clinical pharmacology, GlpT is highly significant as the primary portal for the entry of the antibiotic fosfomycin into the bacterial cell. Fosfomycin mimics the chemical structure of glycerol-3-phosphate, exploiting the GlpT transport system to reach its intracellular target, the enzyme MurA. Consequently, mutations that lead to the loss or downregulation of GlpT are a major cause of clinical resistance to fosfomycin. Structurally, GlpT is a prototypical MFS transporter with 12 transmembrane helices, and its characterization has provided fundamental insights into the alternating-access mechanism of membrane transport.

Other names

Glycerol-3-phosphate permeasesn-glycerol 3-phosphate:phosphate antiporterG3P transporterGlycerol-3-phosphate:phosphate antiporter

Fosfomycin acts as a structural analog of glycerol-3-phosphate and is actively transported into the bacterial cytoplasm via GlpT, where it subsequently inhibits the enzyme MurA to block cell wall synthesis.