Compare and contrast mode of action of penicillin and vancomycin: Why penicillin is still an effective antibiotic today

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2020-05-05

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Abstract

Penicillin is a group of antibiotics that contains β-lactam, which prevents peptidoglycan crosslinking and indirectly bursts bacterial cell walls. It is widely used today against many infections caused by staphylococci and streptococci bacteria. Although antibiotics were effective at treating disease in the early development of these treatments, the late 20th century has seen an increase in antibiotic resistance. However, penicillin-derived antibiotics are still used today through generations and we see fewer cases of resistance to this antibiotic. Understanding the interactions between penicillin and bacterial proteins would be useful for studies on counteracting antibiotic resistance. Other antibiotic called Vancomycin was compared with penicillin because vancomycin resistance is arising in late 20th century like Vancomycin-resistant Enterococcus. Computational methods were used to propose interactions between 6I1E and comparable ligands to understand what the mode of action of penicillin is. It was found that SER294 likely interacts with the carboxylic acid functional group. Additionally, assessment of vancomycin resistance provided a case study for understanding how resistance happens. Comparison of interactions between ligands and residue suggested that GLN67 and ALA88 were the key residues and mutations from Δ110 to 115 showed the significant loss of activity against substrate. This paper highlighted that each antibiotic reacts with hydrogen bond interaction between ligand and residues. In penicillin, amoxicillin and carbenicillin interacted through hydrogen bond. In vancomycin, it likely interacts through hydrogen bonding in D-Ala-D-Ala. Further steps would be choosing antibiotics that work through the same function as penicillin and comparing the structural differences and ligand interactions.

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Molecular Docking, Penicillin-binding protein 3, vancomycin

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