1.2 Destroying or modifying the antibiotic molecule

As you may recall from Week 2, β-lactamases deactivate the β-lactam ring of β-lactam antibiotics, preventing them from binding to their target (Figure 3).

Figure 3 Inactivation of a β-lactam antibiotic by β-lactamase.

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The β-lactamases can deactivate almost all of the β-lactam antibiotics currently in therapeutic use. As you will see in the case study at the end of this week, this includes cephalosporins. Consequently, their presence significantly reduces the available treatment options for infections caused by bacteria expressing β-lactamase. One successful strategy for treating these infections is to combine antibiotic treatment with a β-lactamase inhibitor.

Other antibiotic-modifying enzymes do not destroy or target the core chemical structure that confers antibacterial activity. Instead they modify the antibiotic’s structure by adding chemical groups to prevent it from binding to its target. One group of antibiotics that are particularly susceptible to modification are the aminoglycoside antibiotics which include streptomycin (Figure 4).

Figure 4 Structure of streptomycin. An exposed hydroxyl (-OH) group that can be modified by aminoglycoside-modifying enzymes is highlighted in green (in the figure the hydroxyl group is shown as -HO – this is the same as -OH).

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Aminoglycoside-modifying enzymes add bulky chemical groups to the exposed hydroxyl (-OH) and amino (-NH₂) groups of the antibiotic, which prevent it from binding to its target.