Question

How do \(\beta\) -lactam antibiotics such as penicillin kill bacterial cells, and what explains bacterial resistance to the antibiotic methicillin?

Short answer

Answer: β-lactam antibiotics kill bacterial cells by inhibiting the action of penicillin-binding proteins (PBPs), which play a crucial role in peptidoglycan synthesis, leading to cell wall weakening and eventual bacterial cell death. Bacterial resistance to methicillin primarily occurs due to the presence of the mecA gene, which encodes an altered PBP that has a low affinity for methicillin and other β-lactam antibiotics.

Step-by-step solution

Introduction to β-lactam antibiotics

β-lactam antibiotics, like penicillin, are a group of antibiotics that have a common chemical structure, specifically a β-lactam ring. They are derived from fungi and are widely used for treating bacterial infections. These antibiotics mainly target and inhibit bacterial cell wall synthesis.

Understanding bacterial cell wall synthesis

In bacterial cells, the cell wall provides support, protection, and shape. It is made of peptidoglycan, a polymer composed of sugar molecules (N-acetylglucosamine and N-acetylmuramic acid) and short amino acid chains. This structure ensures the cell wall's rigidity and strength. The synthesis of peptidoglycan is a crucial step in bacterial reproduction, as a new cell wall must be formed for both daughter cells.

The action of β-lactam antibiotics on bacterial cell wall synthesis

β-lactam antibiotics act by inhibiting the action of enzymes called penicillin-binding proteins (PBPs), which are essential for the transpeptidation process (crosslinking of amino acid chains) in peptidoglycan synthesis. When the β-lactam ring binds to the active site of the PBP, it forms a stable acyl-enzyme complex, preventing the proper synthesis of peptidoglycan. As a result, the bacterial cell wall becomes weak and unstable, eventually leading to cell lysis and the death of the bacterial cell.

Methicillin — a specific β-lactam antibiotic

Methicillin is a type of β-lactam antibiotic belonging to the penicillin group. It has been widely used to treat bacterial infections caused by Staphylococcus aureus and other gram-positive bacteria. However, over time, some bacteria have developed resistance to methicillin, rendering it ineffective for some infections.

Bacterial resistance to methicillin

Bacterial resistance to methicillin primarily occurs due to the presence of a gene called mecA, which encodes an altered PBP called PBP2a. PBP2a has a low affinity for binding with β-lactam antibiotics, including methicillin. This means that the antibiotics are unable to efficiently inhibit peptidoglycan synthesis as they do with other PBPs. Bacteria carrying the mecA gene, such as methicillin-resistant Staphylococcus aureus (MRSA), can continue to synthesize their cell walls and survive in the presence of methicillin. In conclusion, β-lactam antibiotics, like penicillin, kill bacterial cells by inhibiting peptidoglycan synthesis, leading to cell wall weakening and eventual bacterial cell death. Bacterial resistance to methicillin can be explained by the presence of the mecA gene, which encodes a modified PBP with a low affinity for methicillin and other β-lactam antibiotics.