Exploring the TEM β-Lactamase in

Background: Urinary tract infections (UTIs) caused by Purpose: In this study, we analyzed a single Methods: The Results: Molecular docking analysis revealed that first-generation cephalosporins, such as cefazolin and cephalothin, exhibited strong binding affinities to TEM-1 β-lactamase (ΔG ≈ -8 kcal/mol) yet were resistant in vitro testing, indicating susceptibility to enzymatic hydrolysis. In contrast, second to fourth-generation cephalosporins (eg, cefuroxime, cefotaxime, cefepime) maintained similar binding energies but demonstrated sensitivity, suggesting enhanced structural resistance to β-lactamase. Aminoglycosides and fluoroquinolones showed varying binding affinities but retained in vitro activity, likely due to their distinct mechanisms targeting ribosomes or DNA gyrase, unaffected by TEM-1. Carbapenems, with lower binding energies, remained effective, consistent with their known β-lactamase resistance. These findings highlight the complexity of resistance, where binding energy alone does not determine antibiotic efficacy. Conclusion: Molecular docking and dynamics simulations revealed that later-generation cephalosporins, carbapenems and aminoglycosides exhibit stable binding and structural resilience against TEM-1 β-lactamase. Despite strong docking and stable interactions observed for first-generation cephalosporins, their clinical inefficacy is due to enzymatic hydrolysis. These findings emphasize that integrating computational binding and stability data with structural and clinical insights is crucial for predicting effective antibiotics against TEM-1-mediated resistance.