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UhpT is a bacterial hexose-6-phosphate:phosphate antiporter belonging to the Major Facilitator Superfamily (MFS). It functions as a membrane-bound transporter that facilitates the uptake of hexose phosphates, such as glucose-6-phosphate, from the extracellular environment or host cytoplasm into the bacterial cell in exchange for internal inorganic phosphate. This transport system is vital for the metabolic adaptation and virulence of pathogens like Staphylococcus aureus and Escherichia coli, enabling them to exploit host-derived nutrients during infection. UhpT is clinically significant as the primary portal for the entry of the antibiotic fosfomycin, which acts as a structural mimic of glucose-6-phosphate. Once inside the cell, fosfomycin inhibits the enzyme MurA, disrupting cell wall synthesis and leading to bacterial death. Resistance to fosfomycin frequently arises through mutations or deletions in the uhpT gene or its regulatory components (UhpABC), which reduce drug accumulation within the bacterium. Consequently, UhpT is a key focus in understanding antibiotic susceptibility and developing strategies to overcome drug resistance in bacterial pathogens.
Transporter-mediated antibiotic uptake
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