2.1.1 Modifying the antibiotic target

As you already know, antibiotics are selectively toxic because they target structural features or cellular processes in the bacterial pathogen that are different or lacking in the host’s cells. Recall how penicillin and other related β-lactam antibiotics work by binding to penicillin-binding proteins (PBPs), preventing them from binding to their normal target, peptidoglycan. Or how trimethoprim prevents dihydrofolate reductase reacting with dihydrofolic acid.

Changes to the structure of the target that prevent efficient antibiotic binding but still enable the target to carry out its normal function will confer antibiotic resistance (Figure 16).

Figure 16 Schematic diagram showing how structural changes in a target enzyme can lead to antibiotic resistance. The substrate is the chemical on which the target enzyme acts. It binds to the enzyme and is converted into a product or products through the action of the enzyme.

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This schematic diagram shows an antibiotic-sensitive target protein molecule (in red). It has an antibiotic-binding site which is close to its substrate-binding site, so that when the antibiotic (in green) is bound, the substrate (in blue) is excluded. A mutation that alters the structure of the target protein such that it no longer has an antibiotic-binding site makes the target antibiotic-resistant as it can now bind its substrate in the presence of the antibiotic.

Figure 16 Schematic diagram showing how structural changes in a target enzyme can lead to antibiotic resistance. The substrate is the ...

This resistance strategy is widespread among bacteria. Altering the structure of the PBP, for example, is one way that bacteria develop resistance to penicillin.