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Bacterial glycolytic enzymes and carbohydrate transport systems are fundamental to the survival, growth, and virulence of pathogenic bacteria by facilitating the acquisition and processing of carbon sources. The carbohydrate transport systems, most notably the phosphoenolpyruvate-dependent phosphotransferase system (PTS), mediate the concomitant uptake and phosphorylation of sugars, providing a direct link between nutrient availability and metabolic regulation (Saier et al., 2005, PMID: 15659677). Once inside the cell, sugars are processed through the glycolytic pathway, involving highly conserved enzymes such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), enolase, and pyruvate kinase, which generate ATP and essential biosynthetic intermediates (Wolfe, 2015, PMID: 25731616). These systems are considered promising therapeutic targets because their inhibition can lead to metabolic collapse and bacterial death, particularly in environments where alternative energy sources are scarce (Richardson et al., 2015, PMID: 26150531). However, the high structural similarity between many bacterial glycolytic enzymes and their human counterparts poses a significant challenge for achieving selective toxicity (Pancholi, 2001, PMID: 11336833). Current drug discovery efforts focus on identifying unique bacterial motifs or targeting the PTS, which is absent in eukaryotes, to develop narrow-spectrum or broad-spectrum antibiotics (Galinier & Deutscher, 2017, PMID: 28814658).
Inhibition of essential metabolic enzymes or transport proteins to disrupt ATP production and biosynthetic precursor availability, leading to bacterial growth inhibition or death.
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