Mechanisms of Antibiotic Action

By Dillon Lim - Medicine Student @ Brasenose College, Oxford

 

Antimicrobials are drugs that stop the proliferation of or kill microbes – bacteria, fungi or viruses. Of course, antibacterials are antimicrobials that work against bacteria. There isn’t often a very clear distinction between the term antibacterials and antibiotics, but certainly antibiotic does have a more medicinal connotation (whereas you could use antibacterial to talk about a wet wipe, for instance).


Antibiotics themselves can be split into the bactericidal (i.e. they kill bacteria) or bacteriostatic (i.e. they prevent further growth). You might think that in all cases, we’d want to go for a bactericidal agent over a bacteriostatic agent, but often preventing further bacterial proliferation and spread of the infection is enough for our immune system to get a good enough handle and take care of it itself.


As a general principle, antibiotics have to specifically target aspects of bacterial metabolism, so that they don’t end up also damaging human cells. Thankfully, given that bacteria are prokaryotes and we are eukaryotes, there are several options available to us. We’ll talk about a few of the common classes of antibiotics here. The β-lactams are a class of antibiotics that work by inhibiting the formation of cross-links between layers of peptidoglycan in the bacterial cell wall. A failure to cross-link the cell wall usually results in a bacterium triggering a kind of ‘self-destruct’ mechanism and lysis of the cell. The most famous of the β-lactams is of course penicillin, the first antibiotic serendipitously discovered by Fleming and later developed by Florey and Chain. These days, we have many different β-lactams outside the penicillin family: the cephalosporins and carbapenems.


Other drugs target bacterial protein synthesis. Bacteria have different ribosomes: two subunits, 50S and 30S, combining to form the 70S subunit. Antibiotics such as the tetracyclines bind to the P site of a ribosome to prevent the formation of a peptide bond between the growing polypeptide and an incoming amino acid. Antibiotics from the aminoglycoside family, including gentamicin, sit on the A site instead to prevent the entry of charged tRNAs.


DNA production is also another important target. One of the important stages in DNA replication is the unwinding of the double helix by topoisomerase enzymes. Quinolones, such as ciprofloxacin, are able to inhibit bacterial topoisomerases, and thus replication. Tetrahydrofolate (THF) – or more commonly known as folic acid – is a nutrient that we obtain from our diets, and is necessary for the production of the individual nucleobases, such as adenine and thymine, that make up DNA. Bacteria on the other hand need to produce these from other molecular precursors, including p-aminobenzoic acid (pABA). Sulphonamides have structural elements very similar to pABA, and thus exert a competitive inhibition on an early stage of THF synthesis. They are also used in combination with trimethoprim, a drug that inhibits the final stage of THF synthesis through a similar mechanism.


Finally, some drugs are able to simply break through bacterial membranes by acting as weak detergents. Polymyxin E is one example. Drugs in this class are a lot rarer – simply because bacterial phospholipid membranes aren’t that much different from human phospholipid membranes, and so finding drugs with the right specificity is difficult!


Further reading:

  1. Overview of Antibiotics. https://www.msdmanuals.com/en-gb/home/infections/antibiotics/overview-of-antibiotics

  2. Overview of Antibacterial Drugs. https://www.msdmanuals.com/en-gb/professional/infectious-diseases/bacteria-and-antibacterial-drugs/overview-of-antibacterial-drugs?query=Overview%20of%20Antibiotics

  3. A Brief Overview of Classes of Antibiotics. https://www.compoundchem.com/2014/09/08/antibiotics/

  4. Classification of Anti‐Bacterial Agents and Their Functions. https://www.intechopen.com/chapters/55303