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The Unspoken Hero of World War II

Contrary to popular belief, each antibiotic has significant pharmacokinetic and pharmacodynamic properties that affect its efficacy, in dependence with the dosage and type of infection. Pharmacokinetics refers to the movement of the drug from consumption until it is removed from the body. It determines concentration of the drug. Pharmacodynamics refers to the time taken by the drug to work its effect when it reaches the site of infection and hence, determines the duration of drug therapy1


Since Alexander Fleming’s discovery of Penicillium notatum, posters and magazine covers of the 1930s and 40s were filled with statements synonymous with, “Thanks to penicillin, he will come home” or “Penicillin saves lives”. Almost a century later, these miracle drugs, collectively called ‘antibiotics’ are still actively in use for quick recovery from infections2.  Antibiotics are defined as chemicals produced by microbes that can destroy or inhibit the growth of a bacteria. They are either bacteriostatic (prevent bacterial growth) or bactericidal (kill bacteria)3

Mode of action of antibiotics. Antibiotics can inhibit the growth of... |  Download Scientific Diagram
Mechanisms of Antibiotics

Antibiotics can be classified into five classes of bactericidal and bacteriostatic drugs, based on their mechanism of action4. Using scientific thinking-based research, the modes of action were identified to target molecular processes that are unique to bacteria. This way, the treatments are specific and potent only to the infectious agent, while the human (host) cells are preserved from its effects. Each class is capable of inhibiting a crucial stage of the central dogma of molecular biology such as DNA replication, protein transcription and translation or aim to disrupt metabolic pathways or cellular components of the bacterium. This part of the series on Antibiotics details you on the mechanism of action of each class of antibiotic.  

  1. DNA synthesis inhibitors

The synthesis of bacterial DNA requires the assistance of enzymes such as DNA polymerases, ligases and topoisomerases. Among the many major steps of eukaryotic and prokaryotic DNA replication that are similar, this class of antibiotics target the enzymes significant to prokaryotes. For example, DNA gyrase which is required for the catalysis of ATP-dependent supercoiling of circular DNA is not present within eukaryotes5. Hence, fluoroquinolones, a group of antibiotics belonging to this class, aim to inhibit the function of DNA gyrase by interacting with its B subunit. Thereby, this class is useful for the treatment of many diseases including skin, bone and urinary tract infections6

  1. Transcription inhibitors

The synthesis of RNA using a DNA template refers to transcription. Here, RNA polymerase required for the initiation stage of transcription differs between prokaryotes and eukaryotes. Transcription inhibitors such as Rifamycin are capable of inhibiting the enzyme by binding to it. The binding affinity to eukaryotic RNA polymerases is 102 to 104 folds lower, making them specific in targeting a broad spectrum of bacteria that cause diseases such as leprosy, tuberculosis and AIDS-associated mycobacterial infections, without affecting the host7.

  1. Protein synthesis inhibitors

This class of antibiotics are considered ‘broad-spectrum drugs’ due to their ability to treat a varied list of infections such as acne, community-acquired respiratory diseases and sexually transmitted diseases. Tetracycline, a drug of this class inhibits protein synthesis in bacteria by binding to a single high affinity site of the 30s ribosome, so that the binding of aminoacyl-tRNA in the 30s ribosome to the mRNA is obstructed. Since eukaryotes contain 40s and 60s ribosomes in place of the 30s ribosome, they are harmless to the host and are only active in bacterial cells8

  1. Metabolic pathway inhibitors

Folate is an important component required for the synthesis of nucleic acids and some amino acids such as methionine. Since prokaryotes uptake folate through the de novo synthesis pathway as opposed to eukaryotes that uptake folate using active transport, they are effective targets for antibiotics. Sulfonamides are such antibiotics that are able to competitively inhibit the enzyme dihydropteroate synthase folate because of its resemblance to the enzyme’s substrate, Para-aminobenzoic acid. Therefore, they are bacteriostatic in nature and are often used in treating urinary tract infections and parasitic diseases9

  1. Cell envelope synthesis inhibitors and disruptors

The cell envelope, which functions as a structural component and a protective layer for the bacteria against internal pressures, consists of a cell wall and a cell membrane. The structure differs between gram positive and gram negative bacteria: the gram negative bacteria have a thin layer of peptidoglycan and a lipopolysaccharide layer, while the gram positive bacteria are absent of the lipopolysaccharide layer but have a thick layer of peptidoglycan10. Hence, antibiotics such as Glycopeptide that inhibit the synthesis of peptidoglycan are effective against gram positive bacteria and antibiotics such as polymyxins that alter the cell membrane structure are effective against gram negative bacteria.

The classifications of antibiotics vary from study to study. Nevertheless, each class has decreased in its effectiveness against infections due to the emergence of antibiotic-resistant bacteria, known as superbugs. One among the many reasons for the development of antibiotic resistance is the misuse of drugs. Therefore, it is important for us to be aware of the classes of antibiotics and the correct combinations that can be used for the treatment of a disease. Currently, scientists world-wide are attempting to develop novel classes of antibiotics that are potent against superbugs. We will learn more about the concept of antibiotic resistance and strategies to combat it in the upcoming segments of the series. 

Written by: Esther Swamidason


  1. Calhoun, C., Wermuth, H. R., & Hall, G. A. (2021, June 8). Antibiotics. Retrieved February 22, 2022, from Nih.gov website: https://www.ncbi.nlm.nih.gov/books/NBK535443/
  2. ‌Quinn, R. (2013). Rethinking Antibiotic Research and Development: World War II and the Penicillin Collaborative. American Journal of Public Health, 103(3), 426–434. https://doi.org/10.2105/ajph.2012.300693
  3. Abushaheen, M. A., Muzaheed, Fatani, A. J., Alosaimi, M., Mansy, W., George, M., … Jhugroo, P. (2020). Antimicrobial resistance, mechanisms and its clinical significance. Disease-a-Month, 66(6), 100971. https://doi.org/10.1016/j.disamonth.2020.100971
  4. Peach, K. C., Bray, W. M., Winslow, D., Linington, P. F., & Linington, R. G. (2013). Mechanism of action-based classification of antibiotics using high-content bacterial image analysis. Molecular BioSystems, 9(7), 1837. https://doi.org/10.1039/c3mb70027e
  5. Windgassen, T. A., Wessel, S. R., Bhattacharyya, B., & Keck, J. L. (2017). Mechanisms of bacterial DNA replication restart. Nucleic Acids Research, 46(2), 504–519. https://doi.org/10.1093/nar/gkx1203
  6. Fluoroquinolones. (2020, March 10). Retrieved February 23, 2022, from Nih.gov website: https://www.ncbi.nlm.nih.gov/books/NBK547840/#:~:text=The%20fluoroquinolones%20are%20indicated%20for,fever%2C%20anthrax%2C%20bacterial%20gastroenteritis%2C
  7. Rifamycin Mode of Action, Resistance, and Biosynthesis. (2022). Retrieved February 23, 2022, from ACS Publications website: https://pubmed.ncbi.nlm.nih.gov/15700959/
  8. Shutter, M. C., & Hossein Akhondi. (2021, July 8). Tetracycline. Retrieved February 22, 2022, from Nih.gov website: https://www.ncbi.nlm.nih.gov/books/NBK549905/
  9. Sanseverino, I., Navarro, A., Loos, R., & Lettieri, T. (2018, December). State of the Art on the Contribution of Water to Antimicrobial Resistance. Retrieved February 26, 2022, from ResearchGate website: https://www.researchgate.net/publication/331703622_State_of_the_Art_on_the_Contribution_of_Water_to_Antimicrobial_Resistance
  10. Silhavy, T. J., Kahne, D., & Walker, S. (2010). The Bacterial Cell Envelope. Cold Spring Harbor Perspectives in Biology, 2(5), a000414–a000414. https://doi.org/10.1101/cshperspect.a000414


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