Antifungal Drugs: Major Types & Functions

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  • 0:03 Fungal Infections
  • 1:17 Target: Plasma Membrane
  • 3:35 Target: Cell Wall
  • 4:10 Target: Nucleic Acid Synthesis
  • 4:54 Target: Microtubules
  • 5:27 Lesson Summary
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Lesson Transcript
Instructor: Katy Metzler

Katy teaches biology at the college level and did her Ph.D. work on infectious diseases and immunology.

Even though the word fungus brings up nasty images in our minds, many fungi are totally harmless. Still, some fungi can cause dangerous infections. In this lesson, learn about antifungal drugs and how they can specifically kill fungi, even though our own cells are similar to fungal cells in many ways.

Fungal Infections

Fungus. Even the word sounds gross. However, from mushrooms to molds to yeasts, fungi are actually pretty cool organisms! And, without them, we wouldn't be able to eat Portobello mushroom burgers, or drink beer or wine! But, they're not so cool when they cause infections, like athlete's foot, yeast infections, thrush and toenail fungus. In addition to these relatively mild fungal infections, more severe, systemic fungal infections are becoming more common in immunocompromised patients, such as those suffering from AIDS. These patients can get opportunistic infections caused by fungi that are around us all the time, but are normally harmless. So, it's definitely very important to have good antifungal drugs.

The problem is that fungi, being eukaryotes, are very similar to our own cells, so it's hard to find drugs that are selectively toxic. Unfortunately, there aren't that many antifungal drugs available today, and the ones that we have can cause major side effects, so they're often only used for infections that are really life-threatening. In this lesson, we'll look at the major types of modern antifungal drugs, and see how they attempt to selectively target fungi without harming our own cells too much.

Target: Plasma Membrane

Remember that one of the major targets for magic bullets, or selectively toxic drugs, was the microbial plasma membrane. But, wait a minute, all cells have plasma membranes, and eukaryotic cell membranes must be pretty similar to each other, right? So, how could a drug only target fungal plasma membranes, and not our own?

The answer is that fungi and animal cell membranes have different sterols, which are special lipids that can regulate membrane fluidity. You've probably heard of cholesterol, which is the major sterol in animal cell membranes. Fungal membranes have ergosterol instead. So, many antifungal drugs target ergosterol as a way to disrupt the fungal plasma membrane. These drugs make fungal membranes very permeable, meaning that cellular contents can leak out and molecules from the outside can get in. This causes the fungus to die, so these agents are usually fungicidal.

Polyenes, such as Amphotericin B, are important drugs for treating systemic fungal infections. They attack ergosterol, injuring fungal membranes. Amphotericin B is an ingredient in topical preparations to treat thrush, which is a yeast infection in the mouth. Remember that when a drug is used topically it means that it is only used on a small region of the body. In contrast, giving a drug systemically means that the drug is distributed throughout the whole body. Amphotericin B is pretty harmless when used just in the mouth, but when given systemically as an IV, this drug is very toxic, especially to the kidneys and liver. It's so toxic that it is sometimes nicknamed 'Amphoterrible'. This drug is given as an IV only in extreme cases, for example systemic fungal infections.

The next group of antifungal drugs is the azoles. These drugs inhibit the synthesis of ergosterol, which means they block the synthesis of the fungal plasma membrane. A couple of these drugs, like clotrimazole and miconazole are mainly used topically, for example, in creams to treat athlete's foot and yeast infections. Another related drug, ketoconazole can be used systemically and is often used as an alternative to the more toxic Amphotericin B. Finally, fluconazole is even less toxic and even more water-soluble. That means it is easier and more effective for systemic fungal infections.

Target: Cell Wall

Another option for selectively killing fungi is to target their cell walls. Remember that animal cells don't even have cell walls. And, fungal cell walls contain certain unique molecules that are not found in any other organisms. The echinocandins are a relatively new class of antifungal drugs that prevent fungi from making beta-glucan, an important component of their cell walls. When a fungus is treated with an echinocandin, it makes an incomplete, weak cell wall, which causes the fungus to lyse, or burst. This is similar to how penicillin kills bacteria.

Target: Nucleic Acid Synthesis

Flucytosine is another commonly-used antifungal drug. It is fungistatic because it blocks DNA and RNA synthesis and, thus, prevents the fungus from making the new DNA and proteins that it needs to reproduce. How does this drug not affect our own nucleic acid synthesis? It's actually pretty cool: flucytosine is a pro-drug, meaning it's not toxic at first. Inside fungal cells, an enzyme converts flucytosine into 5-fluorouracil, which is the active drug. Our cells don't have this enzyme, so we aren't affected. Unfortunately, fungi can rapidly develop resistance against flucytosine, so it is usually given in combination with another drug, like Amphotericin B, to make drug resistance more difficult to achieve.

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