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Schematic of a bacterium, showing DNA, mRNA, a ribosome, and the cell wall, and disruption by inhibition of nucleic acid synthesis, RNA polymerase, protein synthesis or cell wall synthesis, or disruption of cell wall
Antibiotic actions, illustration by Laura Olivares Boldú

How do antibiotics work?

You have bacterial infection and are prescribed an antibiotic by a doctor. Within a few days you begin to feel better.

But how do antibiotics work? In broad terms antibiotic work either by killing the bacteria or by preventing it growing. Antibiotics that kill a bacteria are called ‘bactericidal’ and antibiotics that prevent bacterial growth are called ‘bacteriostatic’.

In general terms, antibiotics work by damaging essential parts of the bacterial cell structure, or by preventing essential cellular functions taking place.

Broadly antibiotics target:

  1. The bacterial cell wall and membrane
  2. DNA synthesis
  3. Protein production

Although these broad groups are useful for classification purposes, different antibiotics work in different ways to affect these processes and structures.

Antibiotics targeting the bacterial cell wall and membrane

Penicillin was the first broad spectrum antibiotic to be discovered. Penicillin is part of the family of antibiotics known as β-lactams (beta-lactam). β-lactam antibiotics are so called because they all share common chemical structure known as a β-lactam ring. β-lactam family includes the penicillins, cephalosporins and carbapenems - which are some of the clinically most important antibiotics.

β-lactam antibiotics kill bacteria by binding to a bacterial enzymes called penicillin-binding proteins (PBPs). These PBPs crosslink (join together) parts of the peptidoglycan layer of bacterial cell walls. By binding the PBPs β-lactams stop the PBPs working to build or repair the bacterial cell wall meaning the bacterial cells break open and die.

Another family of antibiotics known as the glycopeptides antibiotics which includes vancomycin (an important antibiotic used for treating infections resistant to β-lactams) also prevent the cell wall forming by inhibiting peptidoglycan synthesis.

By contrast, daptomycin, a lipopeptide antibiotic, damages the cell membrane by inserting itself into the cell membrane and inducing membrane depolarization. Likewise, colistin, a polymyxcin antibiotic used in the treatment of multi-drug resistant bacteria, binds to the outer membrane causing damage to the cell membrane.

DNA synthesis

Three families of antibiotics prevent DNA synthesis though different mechanisms. Trimethoprim and Sulfamethoxazole (a sulfonamide - the first real antibiotics) both block the activity of enzymes that are involved the synthesis of folic acid. Without folic acid the bacteria are unable to synthesise the DNA bases (A, T, C, G).

The third family of antibiotics is known as the fluoroquinolones (related to quinine which has been used for the treatment of malaria for 400 years). Fluoroquinolones work by binding to an enzyme known as a topoisomerase. Topoisomerase enzymes are involved in the coiling of DNA to form the double helix shape. By binding to the topoisomerase enzyme, fluoroquinolones cause the replication of DNA to stall, meaning that the bacterial cell is unable to replicate.

Protein production

Rifampicin (an important antibiotic for the treatment of tuberculosis) works by binding to RNA polymerase, an enzyme which copies DNA into RNA. RNA is then used as the template to synthesise proteins in the ribosome. By blocking the RNA polymerase, rifampicin stops the bacteria producing proteins which are essential for life.

Many families of antibiotics including the aminoglycosides, tetracyclines, macrolides, phenicols, and lincosamides work by binding to parts of the bacterial ribosome blocking its activity. The ribosome is the machinery that reads the RNA template and synthesises proteins (known as translation) by linking together different amino acids.
Other antibiotics such as mupirocin and fusidic acid work by interfering with other bacterial enzymes that work with the ribosome during translation.

Why do you think antibiotics target such essential processes?

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This article is from the free online course:

Bacterial Genomes: Antimicrobial Resistance in Bacterial Pathogens

Wellcome Genome Campus Advanced Courses and Scientific Conferences