3.1.2 Genetic mutations and protein structure

As you already know, 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 that antibiotic from binding. This would make the target insensitive to the antibiotic and bacteria containing this protein would be resistant to the effects of that 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 these resistant bacteria can grow.

Remember 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 20).

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Figure 20 Genetic mutations can alter the amino acid sequence of a protein.
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Part (a) shows the normal sequence of DNA within a gene. This sequence codes for a sequence of amino acids within a protein. Each amino acid is represented as a blue block on a chain. Part (b) shows a mutation in the DNA sequence from part (a). This change is highlighted in orange. The amino acid sequence coded by this DNA sequence is shown. Amino acids are shown as blue blocks on a chain. The amino acid altered by the mutation is shown in brown.

Figure 20 Genetic mutations can alter the amino acid sequence of a protein.

Some changes in the bacterium’s DNA sequence have no effect on the amino acid sequence. Sometimes, however, even though the change in DNA is very small – perhaps a single point mutation – there can be a major effect on 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.

3.1.1 From genetic information to protein function

3.1.3 Transmission of mutations by vertical gene transfer