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Inhibitors of Cell Wall Synthesis: Bacitracin, Vancomycin & Mycobacteria-specific Drugs

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  • 0:07 Bacterial Cell Walls
  • 1:56 Inhibition of…
  • 5:24 Mycobacteria-specific drugs
  • 6:26 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.

Cell walls make good targets for antibiotics because bacteria need them for survival and our cells don't even have them! In this lesson, learn how different types of antibiotics kill bacteria by preventing them from making their cell walls.

Bacterial Cell Walls

The discovery of penicillin and how it could selectively kill bacteria without harming patients was an amazing breakthrough in the 1940s, and it led to a drastic decrease in the number of people who died from bacterial infections. Eventually, scientists learned that penicillin kills bacteria by inhibiting their cell wall synthesis. In other words, it stops bacteria from making a strong, correctly-formed outer wall. Nowadays, there are many other antibiotics besides penicillin that also target the bacterial cell wall. In this lesson, we'll learn about a few of these antibiotics and how they work.

Let's quickly review what the bacterial cell wall is, and why it's important. Bacterial cell walls are tough, rigid structures that form a protective outer layer around the bacterial cell and help them resist the effects of osmosis. Remember that osmosis is the tendency of water to flow across a membrane to balance out the number of solute molecules on either side. Without an intact cell wall, bacteria would burst and die because of osmotic stress.

Different bacteria have different cell wall structures, just like the outsides of buildings can have many different designs, but still fulfill the same purposes, namely keeping the outside separate from the inside and protecting the inhabitants from an environment that's sometimes hostile. Let's briefly look at three major types of bacterial cell walls.

The Gram-positive cell wall has a thick layer of peptidoglycan, which is a molecule made of sugars and polypeptides that forms a mesh-like structure. The Gram-negative cell wall also has peptidoglycan, but a much thinner layer of it that is sandwiched in between not one, but two plasma membranes. Finally, the mycobacterial cell wall has a single plasma membrane, a thin layer of peptidoglycan and a layer of mycolic acids, which are special lipids unique to mycobacteria.

Inhibition of Peptidoglycan Synthesis

So, we know what cell walls are and we know that they're important for bacterial survival. It's also important to know that our own cells don't have cell walls. So they make a very good, specific target for an antibiotic. What do all bacterial cell walls have in common? You guessed it, a peptidoglycan layer. Many different antibiotics work by preventing bacteria from making peptidoglycan. This is especially important when the bacteria are dividing, because they need new cell wall material for the new cell that is forming.

As the bacterium starts to replicate, it first elongates to about twice its normal size. While this is happening, more peptidoglycan is being made to compensate for the extra surface area. But when these antibiotics are 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. That means that all of these antibiotics that inhibit peptidoglycan synthesis are bactericidal because they directly kill bacteria.

Let's look at some specific antibiotics and how they target peptidoglycan. First up, the cephalosporins; these are natural antibiotics produced by a mold called cephalosporium, just like penicillin is produced by penicillium molds. Like penicillin, they inhibit cross-linking of peptidoglycan. These drugs have a fairly similar structure to penicillin, with a beta-lactam ring that is necessary for their activity. However, they have a different neighboring ring. This means that the cephalosporins are not destroyed by the beta-lactamases that penicillin-resistant bacteria secrete.

However, cephalosporins are not immune to antibiotic resistance; there are other beta-lactamases that specifically target the cephalosporins. Sneaky little bugs. Finally, like penicillins, cephalosporins work better against Gram-positive bacteria because there is no outer membrane that they have to cross. However, cephalosporins are effective against more Gram-negative bacteria than the natural penicillins are.

Bacitracin is very different than penicillins and cephalosporins, but it still inhibits peptidoglycan synthesis. It is a polypeptide antibiotic derived from a Bacillus bacterium found in a wound on a girl named Tracy. That's how it got its name. Bacitracin inhibits peptidoglycan synthesis at an earlier step than the penicillins and cephalosporins. It inhibits the synthesis of the linear strands of NAG and NAM, two sugars that make up the major part of the peptidoglycan matrix.

Bacitracin also works best against Gram-positive organisms. It is only used topically on small regions of the body. For example, in creams you use at home to sterilize small wounds. That's because it has toxicity problems if it is taken systemically, that is, if the drug is distributed through the whole body.

The next drug, vancomycin, is a glycopeptide antibiotic produced by Streptomyces bacteria. It prevents NAG and NAM from being incorporated into the peptidoglycan matrix. Like other cell wall synthesis inhibitors, vancomycin has a narrow range of activity because it can't penetrate well into Gram-negative bacteria. However, it has been very important in combating drug-resistant pathogens, such as MRSA, or methicillin-resistant Staphylococcus aureus, which you can learn about in another lesson. Now, bacteria are even becoming resistant to this important drug, so doctors can't depend on it as a last resort anymore.

Mycobacteria-Specific Drugs

Remember that mycobacteria have a different cell wall than most other bacteria because their cell wall contains mycolic acids. Let's take a look at two antibiotics that specifically inhibit mycobacteria, like those that cause tuberculosis and leprosy, by targeting mycolic acids.

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