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Klebsiella pneumoniae carbapenemase (KPC) is a potent Class A serine beta-lactamase that provides bacteria with extensive resistance to a wide range of beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems (Papp-Wallace et al., 2011). First identified in Klebsiella pneumoniae, this enzyme has rapidly spread to other Gram-negative pathogens via mobile genetic elements like plasmids, making it a primary driver of carbapenem-resistant Enterobacteriaceae (CRE) infections (CDC, 2023). KPC acts by catalyzing the hydrolysis of the beta-lactam ring, effectively neutralizing the antibiotic's ability to inhibit bacterial cell wall synthesis (UniProt, 2024). Clinically, KPC-producing organisms are associated with severe, difficult-to-treat infections such as sepsis, pneumonia, and complicated urinary tract infections, often resulting in high mortality. To combat this resistance, modern medicine utilizes specific beta-lactamase inhibitors like avibactam, vaborbactam, and relebactam, which bind to and deactivate the KPC enzyme, thereby restoring the efficacy of co-administered antibiotics (StatPearls, 2023). Despite these advancements, the ongoing evolution of KPC variants that can evade these inhibitors presents a continuous threat to global public health.
Inhibition of the enzyme's catalytic activity through covalent or non-covalent binding to the active site serine residue, preventing the hydrolysis of beta-lactam antibiotics.
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