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The bacterial glycolytic pathway, primarily the Embden-Meyerhof-Parnas (EMP) pathway, is a fundamental metabolic sequence that converts glucose into pyruvate, generating adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) [3, 16]. It serves as the primary energy-producing pathway in many bacteria and provides essential carbon intermediates for the biosynthesis of amino acids, lipids, and nucleic acids [3, 8]. In pathogenic bacteria, glycolytic enzymes often exhibit moonlighting functions, such as binding to host proteins like plasminogen to facilitate tissue invasion and immune evasion [3, 12]. Targeting this pathway is a strategy for developing new antimicrobials, particularly against multidrug-resistant strains like MRSA and Mycobacterium tuberculosis [1, 4]. However, the high degree of structural conservation between bacterial and human glycolytic enzymes poses a significant challenge for achieving selective toxicity [6, 11]. Current therapeutic strategies involve identifying specific inhibitors for bacterial-specific isoforms or regulatory pockets within these enzymes [3, 10].
Inhibition of specific enzymes within the glycolytic pathway (e.g., GAPDH, Enolase, Pyruvate kinase) to deplete cellular ATP and metabolic intermediates, leading to growth arrest and reduced virulence.
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