How can antibiotics kill bacteria but not harm our own cells? In this lesson, learn about the selective toxicity of antibiotics and antimicrobial drugs and some basic mechanisms for their activity.
Paul Ehrlich and the ‘Magic Bullet’
In the late 1800s and early 1900s, when Paul Ehrlich was studying microorganisms and how to stain them for microscopy, he imagined the idea of a ‘magic bullet’ – a chemical that could specifically kill microbes but not harm the host’s own cells.How could such a ‘magic bullet’ work? Aren’t all cells vulnerable to toxic chemicals? What kinds of chemicals could be selectively toxic only for microorganisms like bacteria, fungi and parasites and not damage our own cells?To find antimicrobial drugs, you’d have to exploit the differences between our cells and microorganisms. It’s true that a lot of the most important proteins involved in basic cellular functions have been conserved throughout evolution, which means there are many similarities among all types of cells in the world. However, our cells are still very different from microorganisms in many ways, and these differences provide drug targets that we can make use of.Antimicrobial drugs are chemicals that are intended to have selective toxicity against microbes, meaning that they kill microbial cells but not the host’s cells. Antimicrobial drugs include antibiotics, which were originally defined as substances produced by microorganisms that inhibit other microorganisms.
The name ‘antibiotics’ comes from the word ‘antibiosis’. Unlike symbiosis, where two organisms live together in a way that is often mutually beneficial, antibiosis is when one microorganism tries to kill another one.Nowadays, the definition of antibiotics has changed a bit. When people say ‘antibiotics,’ they usually mean substances that inhibit bacteria.
And instead of always being derived from microorganisms, many antibiotics nowadays are made synthetically or semi-synthetically. This means that all or part of the drug molecule is made by chemists in the lab.Antimicrobial drugs also include antifungal drugs, antiviral drugs and antiparasitic drugs. These are chemicals that inhibit fungi, inhibit viruses and inhibit parasites.In this lesson, we will learn about the problem of selective toxicity and some different ways that antimicrobial drugs achieve it.
Imagine that you are a scientist trying to design a ‘magic bullet’ that will target a microbe but not cause any damage to the host’s own cells. In other words, you are trying to design a drug that is selectively toxic.
Remember that selective toxicity is the specific inhibition of some types of cells but not others. In the case of antimicrobial drugs, we want the drug to be selectively toxic for whatever microorganism is infecting us and not kill our own cells.How would you go about designing this drug? First, you would think about the differences between microbes and human cells. As you might imagine, selective toxicity is easier to achieve for bacteria than for eukaryotic pathogens. That’s because bacteria, being prokaryotes, are very different from our own cells.Since eukaryotic pathogens, such as fungi and parasites, are much more similar to animal cells, you would have a harder time designing drugs against these microbes.
If you did find some, they would usually cause some degree of toxicity to the patient as well, which means there might be unwanted side effects when using these drugs.
General Classes of Antimicrobial Drugs
Nowadays, we know a lot more about microbes than people did in Paul Ehrlich’s day, so I think you’re going to have no problem designing a selectively toxic antimicrobial drug.What’s a good target to start with? Hmmm… How about the cell wall? Bacteria need intact cell walls in order to survive, and animal cells don’t even have cell walls. Sounds perfect! This strategy really works. Many successful antibiotics that are used today inhibit cell wall synthesis. When bacterial cell walls are weakened, the bacteria lyse, meaning they break open and die.Okay, what could we try next? What other important cellular properties are different in microbes and in animal cells? How about the plasma membrane? If you damage a cell’s plasma membrane, important contents can leak out and the cell can die.
But wait a minute… all cells have plasma membranes, right? That’s true, but there are some major differences that you could exploit for your ‘magic bullet.’ For one thing, bacteria tend to have a different surface charge than animal cells, because many bacterial surfaces are covered with negatively charged molecules, like lipopolysaccharide or teichoic acid. For this reason, plasma membrane-disrupting antibiotics that are positively charged bind more easily to bacterial surfaces than to animal cell surfaces. And fungal and animal cell plasma membranes share many similarities because they are both eukaryotes, but they are composed of a few different lipids. Many modern antimicrobial drugs target microbial plasma membranes using these different characteristics.
All right, we’ve made good use of the outsides of microbes to selectively target them for destruction. So what about intracellular contents? Can you think of any important intracellular functions that we could specifically target?How about protein synthesis? All cells need to make proteins in order to survive and replicate. You might ask how an inhibitor of protein synthesis could be selectively toxic.
Microorganisms and higher eukaryotes all use ribosomes to synthesize proteins. However, the structure of the ribosome is different in bacteria than it is in eukaryotes. In fact, many antibiotics interfere specifically with bacterial ribosomes.
Even so, these drugs can cause some toxicity to the patient because our mitochondria have ribosomes that are very similar to bacterial ribosomes. Why is that? Scientists now believe that, during the evolution of eukaryotic cells, mitochondria were originally derived from bacteria.All right, we’re doing pretty well here but there are still a couple other targets we could use to make our ‘magic bullets.’ Hmmm; Well, if targeting protein synthesis worked pretty well, what about targeting nucleic acid synthesis? All cells need to make DNA and RNA to survive and replicate, but eukaryotes and prokaryotes use slightly different enzymes to do so. There are many antimicrobial drugs that specifically inhibit microbial nucleic acid synthesis.
Let’s think of one last strategy for designing a selectively toxic antimicrobial drug. What about microbial metabolism? Can we prevent microbes from making essential metabolites? Indeed we can. There are some nutrients that we obtain from our food that microbes have to make on their own. Some important modern antibiotics work by preventing microbes from making these metabolites. These drugs don’t cause toxicity to us because we don’t have to produce these nutrients on our own; we just eat them.
In this lesson, we’ve learned that the term antimicrobial drugs refers to a whole class of chemicals that attempt to specifically target microbes. They include antibiotics, which inhibit bacteria and are often derived from microorganisms. Other antimicrobial drugs include antifungal drugs, which inhibit fungi; antiviral drugs, which inhibit viruses; and antiparasitic drugs, which inhibit parasites.We’ve learned that it’s very important for antimicrobial drugs to have selective toxicity, which is specific inhibition of some types of cells but not others.
While thinking of ways to achieve selective toxicity, we discovered some major classes of antimicrobial drugs. These classes are defined by their specific targets in microbes, which are:
- The cell wall
- The plasma membrane
- Protein synthesis
- Nucleic acid synthesis
Many of the antimicrobial drugs we use today exploit differences in all of these targets between microbial and animal cells.
After finishing this lesson, you should be better able to:
- Define antimicrobial drugs and name some specific types
- Explain why it is easier to develop selectively toxic drugs to target prokaryotic pathogens rather than eukaryotic pathogens
- Understand how antimicrobial drugs are classified
- List some of the differences in pathogenic cells that can be exploited in order to develop selectively toxic antimicrobial drugs