Volume 8 Number 1 2025
Structural Insights into TEM-1 β-Lactamase-Mediated Ceftriaxone Resistance in Escherichia coli: A Molecular Docking and Toxicity Analysis
Most Farhana Akter1*, Amena Khatun Manica2, Md Abu Bakar Siddique3, Tufael4, Md. Robiul Islam1, Sabiha Nusrat5
Microbial Bioactives 8 (1) 1-11 https://doi.org/10.25163/microbbioacts.8110447
Submitted: 07 May 2025 Revised: 17 July 2025 Accepted: 24 July 2025 Published: 24 July 2025
Abstract
Background: The escalating resistance of Escherichia coli to Ceftriaxone has become a pressing global concern, undermining the clinical utility of this critical β-lactam antibiotic. Among the underlying mechanisms, the TEM-1 β-lactamase enzyme plays a pivotal role in hydrolyzing β-lactam rings, leading to reduced antibiotic efficacy.
Objective: This study investigated the molecular basis of Ceftriaxone resistance and evaluated structural interactions between TEM-1 and selected β-lactam compounds to guide future therapeutic designs.
Methods: Antibiotic resistance trends (2010–2023) were retrieved from the CDC AR Data Hub and NARMS databases, revealing a steady rise in Ceftriaxone resistance in E. coli. Molecular docking analyses were performed using PyRx with Ceftriaxone, Cefepime, and Avibactam as ligands, and the resulting interactions were visualized through PyMOL and Discovery Studio. Toxicity predictions were conducted using ProTox-II.
Results: Ceftriaxone demonstrated the strongest binding affinity to TEM-1 (-7.8 kcal/mol), forming stable hydrogen bonds with GLU240, GLU104, and SER130. Cefepime exhibited slightly weaker binding (-7.3 kcal/mol) with reduced interaction stability, while Avibactam showed promising π-π and electrostatic interactions, suggesting potential β-lactamase inhibitory effects. Toxicity profiling indicated higher nephrotoxicity and respiratory toxicity risks for Cefepime, highlighting its safety limitations.
Conclusion: Collectively, these findings provide structural and mechanistic insights into TEM-1–mediated resistance and emphasize the need for next-generation β-lactamase inhibitors to sustain the efficacy of β-lactam antibiotics against evolving antimicrobial resistance.
Keywords: Antimicrobial Resistance (AMR), Ceftriaxone Resistance, TEM-1 β-lactamase, Molecular Docking, β-lactam Antibiotics
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