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In this lesson, you will learn about an accidental discovery that changed human history: the discovery of the antibiotic penicillin.

You will also learn how it works and why it’s most effective against Gram-positive bacteria.

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Discovery of Penicillin

Sometimes in life, you make an amazing discovery while trying to do something completely different. In 1928, the Scottish bacteriologist, Alexander Fleming, was going through some old bacterial plates, to clean up his lab a bit, when he discovered this moldy plate. He was about to toss it into the trash can when he noticed something unusual. Around the colony of mold, the bacteria, Staphylococcus aureus, weren’t growing as well.

That’s funny; how could that happen?It turns out that the mold was conducting chemical warfare! It was releasing a compound that could kill bacteria in an attempt to have more space to grow and more nutrients to itself. When a microorganism produces a substance that can kill other microorganisms, it is called antibiosis. You can compare this word to ‘symbiosis,’ which is when organisms live together in a way that is often mutually beneficial. The word ‘antibiotic’ comes from this ‘antibiosis.’The antibiotic-producing mold was identified as a member of the genus Penicillium, and its antibacterial compound was eventually isolated and named penicillin. In the early 1940s, Howard Florey and Ernst Chain carried out the first clinical trials of penicillin, just in time for the drug to be used on wounded soldiers in the final stages of World War II. From that time forward, antibiotics have made a huge impact on human history and drastically reduced the infectious disease burden in the world.

Mechanism of Penicillin

By now, you’re probably super curious about how penicillin actually works. It turns out that penicillin interferes with the synthesis of peptidoglycan in bacterial cell walls. Remember that peptidoglycan is a complex molecule made of sugars and polypeptides that forms a tough, strong lattice that surrounds bacterial cells.

Peptidoglycan is a major component of most bacterial cell walls. The rigid peptidoglycan layer helps bacteria stay intact in the face of osmotic pressure, which is when water tends to flow into or out of a cell to balance out the concentration of solutes on either side of a membrane.Penicillin prevents peptidoglycan from cross-linking properly in the last stages of bacterial cell wall synthesis. This greatly weakens the cell wall and causes the bacterium to lyse, or burst open, because of osmotic pressure. Penicillin is bactericidal because it directly kills bacteria.

And, since peptidoglycan is not found in human cells, penicillin is selectively toxic and does not harm us when we take it. Sounds like a great antibiotic, right?

Penicillin’s Spectrum of Activity

It’s important to remember that penicillin is a narrow-spectrum antibiotic, meaning that it is effective against a relatively narrow range of bacteria. The reason lies in the different types of cell walls that bacteria can have.

Remember that bacteria can be divided into two major groups based on the Gram staining procedure, which stains Gram-positive and Gram-negative bacteria differently because of their different cell walls.Gram-positive bacteria have a single plasma membrane and a thick layer of peptidoglycan that surrounds it. In contrast, Gram-negative bacteria have two membranes with a thin layer of peptidoglycan in between. Penicillin has different effects on these two types of bacteria. In Gram-positive bacteria, penicillin can access the thick peptidoglycan layer very easily. As the bacterium starts to replicate, it first elongates to about twice the normal size. While this is happening, more peptidoglycan is being made to compensate for the extra surface area.

But, when penicillin is present, the peptidoglycan can’t cross-link properly, so the cell wall is very weak in places.Eventually, enough osmotic pressure builds up that the bacterium bursts and dies. Gram-negative bacteria don’t have to worry so much about penicillin, though. Their outer membrane prevents penicillin from penetrating into the periplasm, where the thin layer of peptidoglycan is. However, there are other antibiotics, such as carbenicillin, that are related to penicillin but can penetrate Gram-negative outer membranes better. Gram-negative bacteria are more susceptible to these antibiotics.

Lesson Summary

In this lesson, we learned about Alexander Fleming’s accidental discovery of antibiotics when he found a moldy bacterial plate in his lab.

We learned that antibiosis is when a microorganism produces a substance that can kill other microorganisms, which is kind of like chemical warfare!Next, we learned how penicillin works. It interferes with the synthesis of peptidoglycan. This weakens the cell walls of dividing bacteria, so they burst and die because of osmotic pressure.Finally, we learned that penicillin is a narrow-spectrum antibiotic and is more effective against Gram-positive bacteria. Gram-negative bacteria are protected against penicillin’s effects because they have a protective outer membrane that prevents penicillin from accessing their peptidoglycan layer.

Learning Outcomes

After you’ve finished with this lesson, you’ll be able to:

  • Describe how Alexander Fleming discovered penicillin
  • Define antibiosis
  • Explain how penicillin works against Gram-positive bacteria and why it is not effective against Gram-negative bacteria
  • Identify an antibiotic that is effective against Gram-negative bacteria

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