Mechanism of Action of Antimicrobial Agents

Abstract

Antibacterial and antifungal agents aim to kill pathogens, or at the very least incapacitate them. To achieve this aim these agents must have a reasonable degree of toxicity at the cellular level. If this toxicity was equally manifest against all cell types then the drugs would be unusable in patients as the side effect profile would be unacceptably severe. Selective toxicity, whereby the agents are orders of magnitude more toxic to bacteria or fungi than human cells, allows for the safe and effective administration of these agents to patients. There are a number of different mechanisms by which an antimicrobial agent can yield selective toxicity: ● Target a cellular structure that exists only in bacteria/fungi—e.g. the cell wall; ● Target a cellular structure that has a significantly different structure in bacteria/ fungi— e.g. the ribosome; the fungal cell membrane; ● Target cellular enzymes that are significantly different in bacteria/fungi e.g. topoisomerase; ● Target a synthetic pathway that exists only in bacteria e.g. folate synthesis. Broadly, antibacterial drugs can be divided into the following categories: ● Agents that target the cell wall; ● Agents that target the cell membrane; ● Agents that inhibit protein synthesis; ● Agents that inhibit DNA replication/ transcription of RNA; ● Agents that target folate synthesis; ● Agents that directly damage intracellular structures. The cell wall is unique to bacteria, and therefore an ideal target. Disrupting the complex cross-linking process required to produce the cell wall leads to loss of bacterial cell integrity and therefore to cell death. The following classes of antibiotics target the cell wall: The first class to be discovered, and still in many cases the most effective, incorporates the four-membered beta-lactam ring—its homology to d-alanyl-d-alanine allows beta-lactam-containing compounds to bind to cell wall peptidoglycans and act as chain terminators. The beta-lactam ring is fused to a five-membered sulphur-containing ring. Variations in side chains account for the differing pharmacokinetics and spectra of action of the different compounds—for example, the addition of an amino group to benzylpenicillin produces ampicillin.