Understanding antibiotic resistance
Understanding antibiotic resistance

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Understanding antibiotic resistance

1.2 Genetic mutations and protein structure

As you saw in Week 3, changes in the structure of bacterial proteins can result in antibiotic resistance.

  • Can you think of a specific example of how changing protein structure could lead to antibiotic resistance?

  • Structural changes to an antibiotic target protein could prevent the antibiotic from binding. This would make the target insensitive to the antibiotic and bacteria containing this protein would be resistant to the effects of the antibiotic. For example, linezolid exerts its antibiotic effects by binding to ribosomes and preventing the initiation of protein synthesis. Structural changes to the ribosome can prevent the binding of linezolid. Consequently, protein synthesis initiation is no longer blocked in the presence of linezolid and resistant bacteria can grow.

Recall from Section 1.1 that the amino acid sequence, and therefore the structure of a protein, is encoded in the DNA sequence of a gene. Small changes, or mutations, in the DNA sequence within a gene can alter the amino acid sequence of the protein it encodes (Figure 2).

Described image
Figure 2 Genetic mutations can alter the amino acid sequence of a protein.

It only requires a very small change in the bacteria’s DNA sequence to alter the amino acid sequence and, therefore, the structure of proteins that are targeted by antibiotics. As you have seen, these changes in the structure of proteins targeted by antibiotics can have important consequences for their function.

Recall from Week 3 how changing the structure of the ribosome to prevent linezolid binding results in resistance to this antibiotic. These structural changes are caused by several genetic mutations that alter the amino acid sequence, and therefore the structure, of the ribosome.

In the case study later this week, you will look at how genetic mutations can cause resistance to cephalosporin antibiotics.

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