A Cellular Perspective on Antibiotic Action

This student blog post is written by Ozan D. and is about the antibiotic penicillin: what is it, and how does it work to kill bacteria? Want to learn all about this critical antibiotic to human health (past and present)? Keep reading below! Take it away, Ozan!

Antibiotics are among the most used medications worldwide, yet their widespread use is often misunderstood. In Canada alone, a total of 23,406,640 antibiotic prescriptions were dispensed in 2019, corresponding to a rate of 627.3 prescriptions per 1,000 people (Public Health Agency of Canada, 2020). This striking number suggests that more than half of the population received at least one antibiotic prescription within a single year. However, despite their importance, antibiotics are frequently used improperly or unnecessarily, which contributes to the growing problem of antibiotic resistance (University of Hawaiʻi, n.d.).

Ever since I started taking the cell biology course, understanding how drugs work at the cellular level has become quite fascinating to me. Especially, while conducting research on cancer drugs earlier, learning how these drugs affect specific structures within cells has been a major source of motivation for me. Throughout this process, I realized that understanding a scientific topic and connecting it to real-world problems gives me a great sense of fulfillment. I also thought that explaining the mechanisms of action of antibiotics in a simple and understandable way might help people better understand why they need to use these medications with caution. Therefore, my writing assignment 2 will address the mechanism of action of penicillin on bacteria and its effects.

Antibiotics are medications used to treat bacterial infections and the diseases that result from them by fighting these infections (Memorial Saglik Grubu, n.d.). Antibiotics are classified into different groups based on their mechanisms of action. While some target the bacterial cell wall (such as penicillin), others inhibit protein synthesis or block DNA replication (such as cipro). These different mechanisms disrupt the bacteria’s vital processes, thereby preventing their survival. Antibiotics are used to treat many infection-related illnesses, particularly sore throats and urinary tract (Medline, n.d.). Antibiotics must always be used under a doctor’s supervision, and the appropriate type of medication may vary from person to person. Different dosages or types of antibiotics may be prescribed for children, adults, and individuals with weakened immune systems. Additionally, unnecessary or improper use can lead to bacteria developing resistance to antibiotics. Therefore, the proper and responsible use of antibiotics is of great importance for both individual and public health.

The discovery of antibiotics marked a major turning point in modern medicine (Özdoğan, n.d.). Penicillin, the first antibiotic, was discovered by Alexander Fleming (Özdoğan, n.d.). Alexander Fleming (1881–1955) spent his entire career at St Mary’s Hospital, London, joining in 1906 and discovering penicillin in 1928 (Gerberi, 2024). When Alexander Fleming returned from vacation, he noticed that mold had formed in a petri dish (a small glass container used to culture bacteria in a laboratory) containing bacteria. Seeing that the bacteria were not growing around the mold, he realized that the mold was secreting a substance that killed the bacteria (Ozdogan, n.d.). He later identified the mold as belonging to the Penicillium genus and named the substance “penicillin” (Gerberi, 2024). In the 1940s, Howard Florey, Ernst Boris Chain, and Norman Heatley succeeded in developing penicillin into a usable medication. During World War II, production of this drug began in earnest, and it was used to treat many serious infections. Although Fleming’s discovery demonstrated penicillin’s effect on bacteria, the exact mechanism of this effect was initially unknown. Subsequent scientific studies have shown that penicillin targets the cell wall, which is essential for bacterial survival (Vollmer et al., 2008). To understand how penicillin works, it is first necessary to comprehend how the cell wall functions in bacteria and why it is so crucial.

In bacteria, the cell wall is a rigid outer structure that surrounds and protects the cell (University of Hawaiʻi, n.d.). This structure maintains the bacterium’s shape and prevents it from being damaged by physical forces from the external environment. The most important component of the cell wall is a strong molecule called “peptidoglycan.” Peptidoglycan consists of long sugar chains linked together and short protein bridges that connect these chains. This structure acts like a mesh (or cage), giving the bacterium both strength and flexibility.

As the bacterium grows and divides, this cell wall must be constantly renewed. During this process, specialized enzymes link the peptidoglycan chains to form new bonds and strengthen the wall (Vollmer et al., 2008). However, the cell wall’s primary importance lies in its ability to withstand the high internal pressure. Since the interior of the bacterium is more concentrated than the external environment, water constantly tries to enter the cell. If the cell wall is not strong enough, this pressure causes the cell to swell and eventually burst. Therefore, the cell wall is an indispensable structure for the bacterium’s survival, and this is precisely why penicillin works by targeting the cell walls of bacteria.

With this background, it becomes easier to understand how penicillin targets the bacterial cell wall and why this effect is lethal. In general, penicillin causes bacterial cell walls to rupture. The bacterial cell wall is a strong, mesh-like structure composed of molecules called peptidoglycan as it is mentioned. This structure both gives the bacterium its shape and protects it from the external environment. It also helps the bacterium resist internal pressure. As bacteria grow and multiply, they must constantly renew their cell walls. During this process, the building blocks of peptidoglycan link together to form a sturdy wall. This linking process occurs thanks to special proteins called “penicillin-binding proteins” (PBPs) which help connect these building blocks and strengthen the wall (Wise & Park, 1965). These proteins work like “master builders” to strengthen the cell wall. Penicillin comes into play precisely at this point. The molecules of this drug bind to PBPs, inhibiting their function. As a result, new peptidoglycan bonds cannot form, and the cell wall gradually weakens (Wise & Park, 1965). In other words, the bacterium becomes unable to repair itself. The weakened cell wall cannot withstand the pressure inside the cell. Water moves from the external environment into the cell, and the bacterium begins to swell. Eventually, the weakened wall gives way under this pressure, and the bacterium bursts and dies (University of Hawaiʻi, n.d.). This process is called “lysis,” which refers to the disintegration of a cell by rupture of the cell wall or membrane.

Figure: Mechanism of action of penicillin. The diagram illustrates how penicillin binds to penicillin-binding proteins (PBPs) in the bacterial cell wall, preventing the cross-linking of peptidoglycan chains. This inhibition weakens the cell wall structure, making it unable to withstand internal osmotic pressure, which ultimately results in cell lysis. Image from osmosis.org, reprinted in Science Notes (n.d.)

This mechanism is particularly important because human cells lack a cell wall. Therefore, while penicillin targets bacteria, it causes minimal harm to human cells. However, this does not mean that penicillin is completely without side effects.

One of the most common issues is allergic reactions (Memorial Saglik Grubu, n.d.). These reactions can range from mild skin rashes to serious conditions such as anaphylaxis (severe, life-threatening allergic reaction), which, though rare, can be life-threatening (Memorial Saglik Grubu, n.d.). Additionally, antibiotics can affect not only harmful bacteria but also the beneficial bacteria in our bodies (Memorial Saglik Grubu, n.d.). For example, the bacteria living in our intestines that aid in digestion (the gut microbiota) may be affected by this. This can lead to problems such as digestive issues.

The over-use of antibiotics also has led to a serious global problem known as “antibiotic resistance” (Public Health Agency of Canada, 2020). Over time, bacteria can evolve and develop resistance to antibiotics (Medline, n.d.). For example, while some bacteria produce enzymes that break down penicillin, others alter their target proteins to prevent the drug from binding (Ozdogan, n.d.). This makes treating infections more difficult and necessitates the use of stronger or alternative medications. While rising antibiotic resistance poses a serious threat to modern medicine, it has also made the development of new and more effective antibiotics imperative.

Penicillin is not only an effective antibiotic but also a powerful example of how understanding biological processes at the cellular level can lead to life-saving treatments. Penicillin demonstrates how a single molecular interaction can determine an organism’s survival by disrupting peptidoglycan synthesis. However, the widespread and often improper use of antibiotics has contributed to the rise of antibiotic resistance, which has become a significant global threat today. This situation clearly highlights the importance of using antibiotics responsibly and under medical supervision. Ultimately, establishing the connection between cellular mechanisms and real-world outcomes helps us better understand both the power and the limitations of modern medicine.

Works Cited:

Gerberi, D. (2024). Alexander Fleming: A second look. Journal of the Medical Library Association, 112(1), 55–59. https://pmc.ncbi.nlm.nih.gov/articles/PMC11189133/

Memorial Sağlık Grubu. (n.d.). Antibiyotik nedir? https://www.memorial.com.tr/saglik-rehberi/antibiyotik-nedir

Medline. (n.d.). Tıpta devrim: Penisilin. https://www.medline.com.tr/tipta-devrim-penisilin

Public Health Agency of Canada. (2020). Antibiotic use in Canada. https://pmc.ncbi.nlm.nih.gov/articles/PMC8946648/

Science Notes. (n.d.). Penicillin: History, structure, classification and mechanism antimicrobial activity. https://thesciencenotes.com/penicillin-history-structure-classification-mechanism-antimicrobial-activity/

Özdoğan, D. (n.d.). Penisilin: 1928’de bakteriyel hastalıklarla savaşta devrim. https://www.drozdogan.com/penisilin-1928-bakteriyel-hastaliklarla-savasta-devrim/

University of Hawaiʻi. (n.d.). Weird science: Penicillin and the cell wall. https://manoa.hawaii.edu/exploringourfluidearth/biological/aquatic-plants-and-algae/structure-and-function/weird-science-penicillin-and-cell-wall

Vollmer, W., Blanot, D., & de Pedro, M. A. (2008). Peptidoglycan structure and architecture. FEMS Microbiology Reviews, 32(2), 149–167. https://doi.org/10.1111/j.1574-6976.2007.00094.x

Wise, E. M., & Park, J. T. (1965). Penicillin: Its basic site of action as an inhibitor of a peptide cross-linking reaction in cell wall mucopeptide synthesis. Proceedings of the National Academy of Sciences, 54(1), 75–81. https://doi.org/10.1073/pnas.54.1.75