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Understanding antibiotic resistance
Understanding antibiotic resistance

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2.4 Inhibitors of metabolic reactions

Antibiotics that disrupt essential bacterial metabolic pathways are acting as antimetabolites. These chemicals are structurally similar to natural metabolites but just different enough to interfere with normal cell function.

For example, trimethoprim inhibits the synthesis of folic acid, a vitamin which bacteria, unlike humans, must make themselves. Trimethoprim is a structural analogue of dihydrofolic acid, an intermediate compound in the folic acid pathway. Trimethoprim out-competes dihydrofolic acid to react with a specific bacterial enzyme in the pathway, thereby interrupting folic acid synthesis and inhibiting bacterial growth (Figure 7).

An image of the folic acid pathway.
Figure 7a The folic acid pathway. Trimethoprim prevents the enzyme dihydrofolate reductase reacting with the intermediate compound dihydrofolic acid, thereby blocking the pathway at the point shown.
An image of the underlying competitive mechanism.
Figure 7b The underlying competitive mechanism.

The action of trimethoprim illustrated in Figure 7b exemplifies the specific interaction between antibiotic and bacterial target at a molecular level which disrupts a particular cellular process. You will return to this topic in Week 3 in relation to the development of antibiotic resistance.

In the next section, you will look in detail at the mechanism of ß-lactam antibiotics.