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Bacterial nucleoside transporters are specialized membrane proteins that facilitate the uptake of nucleosides and nucleobases from the extracellular environment into the bacterial cytoplasm (Patching et al., 2005). These transporters, which include the NupC and NupG families in Escherichia coli and other Gram-negative bacteria, are essential for the nucleotide salvage pathway, allowing the cell to recycle preformed genetic precursors instead of relying on de novo synthesis (Young et al., 2013). By scavenging host-derived nucleosides, these systems support bacterial metabolism and replication during infection. In the context of pharmacology, these transporters are exploited as entry points for nucleoside-based antimetabolites and "Trojan horse" antibiotics, which mimic natural substrates to gain access to the cell and inhibit DNA or RNA polymerase (Mulligan et al., 2014). For example, analogs like 5-fluorouridine utilize these pathways to exert bactericidal effects. A major challenge in targeting these proteins is the structural conservation between bacterial transporters and human Equilibrative (ENT) or Concentrative (CNT) nucleoside transporters, which can lead to off-target effects and host toxicity (Paproski et al., 2013).
Facilitated transport or active symport of nucleoside analogs into the bacterial cell to disrupt nucleic acid synthesis or metabolic pathways.
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