Viva La Resistance


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Hash browns, tater tots, baked potato, french fries. Which one would you get rid of and why?

I think I would get rid of baked potatoes. All the other potato products are delicious on their own, but nothing tastes worst than a plain baked potato. If I have free access to cheese, butter, sour cream, and bacon bits, then the potato can stay.

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In September 1928, Sir Alexander Fleming made a discovery that would change the world.

While working with a culture of bacteria, Fleming noticed some mold starting to grow on the petri dish alongside the bacteria. However, he saw that where the mold was growing, the bacteria were not. Intrigued, Fleming grew the mold alongside the bacteria and again noticed that the mold killed the bacteria. He would later figure out that it was not the mold itself killing the bacteria, but some sort of “juice” the mold was producing (mold juice…yum). And thus, the first antibiotic was born: penicillin, so called because the mold producing this bacteria-killing juice belongs to a group of fungi called Penicillium (so creative, Fleming).

But now we’re here, almost one hundred years since Fleming accidentally made a life-changing discovery. What’s happened since then and what does the future look like? Join us, won’t you, while we learn exactly what it means when we talk about antibiotics and resistance (Karina Longworth fans? Anyone?).

The Mighty Antibiotic

So what are antibiotics really? Surely, you’ve taken them at some point in your life for some infection or another, but do you actually know what that little pill or that bubble gum flavored syrup is? Antibiotics are broadly defined as compounds that either stop the growth of, or kill, bacteria. That last word is pretty critical – bacteria. Contrary to what many people think, antibiotics won’t actually cure viral infections like the common cold or the flu (peep Blaide’s article on the basics of HIV for a crash course on viruses).

Organisms such as fungi and bacteria in soil produce antibiotics for a variety of biological uses. Photo credit: Remi Muller

Organisms such as fungi and bacteria in soil produce antibiotics for a variety of biological uses. Photo credit: Remi Muller

Most antibiotics that we know and love today are made by fungi or bacteria that live in the soil. Bacteria and fungi can use them to fend each other off or to communicate with one another. We’ve since been able to synthetically create new antibiotics, as well as modify existing ones (these are called chemical derivatives).

Antibiotics can be broken down into different classes. Each class has its own mechanism of action, or way that it kills the bacteria. Take, for example, Fleming’s penicillin. Penicillin and its derivatives, like amoxicillin, belong to a class of antibiotics called beta lactams (β-lactams). These antibiotics function by binding to proteins made by the bacteria, called Penicillin Binding Proteins (truly, so creative) that are necessary for the bacteria to build their cell walls. When penicillin binds the penicillin binding proteins the bacteria can’t make any more cell wall, causing them to lyse, or pop like little balloons. For a dramatic video of penicillin in action, click here, and make sure your sound is on.

Antibiotics target all different parts of and processes in the bacterial cell. *Note: ribosomes are proteins that are important for making other proteins (are Inception jokes still cool? Cause that’s Protein-ception). Image credit: Lumen Microbiology

Antibiotics target all different parts of and processes in the bacterial cell. *Note: ribosomes are proteins that are important for making other proteins (are Inception jokes still cool? Cause that’s Protein-ception). Image credit: Lumen Microbiology

Other classes of antibiotics, like polymyxins (commonly in triple antibiotic ointment like Neosporin®) can target the bacterial cell membrane, also causing the bacteria to lyse. There are antibiotics that target essential processes in the cell, like DNA, RNA, or protein synthesis. If these processes are disrupted, the bacterial cell will die, although how exactly this death occurs remains hotly debated. Check out the diagram to the right of the different classes of antibiotics and what part of the bacteria they target.

After Fleming discovered penicillin in 1928, the world saw an explosion of antibiotic discovery. Almost every year for the next fifty years, a new class of antibiotics was discovered. However, since 1987 – over thirty years ago – no new class has been discovered. Any “new” antibiotic since the 1987 development of lipopeptides is actually just a chemical derivative of a previously discovered one. Couple that with alarming rates of antibiotic resistance, and it seems we’ve reached an impasse.

While many researchers are still searching for new antibiotics, federal funding for discovery is limited and pharmaceutical company interest in clinical trials for new antibiotics is low. So how did we get to this Post-Antibiotic Era, and what does it mean for global health?

The Post-Antibiotic Era

Almost as quickly as antibiotics were discovered, bacteria were developing resistance to them. Although antibiotic resistance occurs naturally, overuse and misuse by humans and in animals is making the problem much worse. Things like having “leftover antibiotics” (certainly you all always finish the prescribed course…right?), using antibiotics for infections that aren’t caused by bacteria (looking at you again, Common Cold), using antibiotics when you don’t even really have an infection, or using antibiotics in livestock feed as growth promoters, all contribute to the development of resistance.

Antibiotics used in livestock feed may be doing more harm than good. Photo credit: Annie Spratt

Antibiotics used in livestock feed may be doing more harm than good. Photo credit: Annie Spratt

An interesting fact: most industrial livestock feeds incorporate some form of antibiotics to help the animals fight off infection. The thing is, the amount of antibiotic incorporated into this feed is so low, or “subinhibitory,” that it’s not strong enough to truly fight off a bacterial infection. Instead it just breeds antibiotic resistance within the livestock. Additionally, these antibiotics often get washed into nearby streams or rivers, either in the form of feed or animal excrement, and further contribute to antibiotic resistance in the local environment. This is a huge problem.

This infographic shows when antibiotics were commercially introduced versus when resistance was identified. Note that while penicillin was discovered in 1928, it wasn’t in widespread use until 1943, although cases of penicillin resistance were documented as early as 1940).

This infographic shows when antibiotics were commercially introduced versus when resistance was identified. Note that while penicillin was discovered in 1928, it wasn’t in widespread use until 1943, although cases of penicillin resistance were documented as early as 1940).

Looking inside the bacterial cell, resistance can develop when mutations, or changes, spontaneously pop up in the bacterial DNA. These mutations can make the bacteria more “fit,” or better able to survive in the presence of the antibiotic. While the antibiotic will kill any of the bacteria without the mutation, the bacteria with the mutation are able to grow and divide despite antibiotic treatment, resulting in a whole population of resistant bacteria. These resistant bacteria can then be spread from person-to-person, in animals, and in the environment.

Bacteria can also develop resistance to antibiotics by receiving DNA from other bacteria in the environment, a process called horizontal gene transfer (HGT). Similar to spontaneous mutations, HGT can result in bacteria with genes that help them survive in the presence of an antibiotic. You can see in the timeline on the left that resistance has popped up to all currently available antibiotics - sometimes within the same year it was released commercially (hey levofloxacin)! 

Now that we kind of know how we got here, let’s take a second to talk about what this Post-Antibiotic Era might mean for global human health. The Center for Disease Control reports that more than 2 MILLION people just in the United States are diagnosed with an antibiotic-resistant infection every year. Of those 2 million people, about 1% of them will die. That may not seem like a lot, but that 1% is more than 20 THOUSAND people – more than the number of seats in Madison Square Garden in Manhattan.

Remember that these infections would’ve been completely treatable a few decades ago when these antibiotics were first introduced. Not to go full Doomsday on you, but recently a report by the World Health Organization found that some regions of the world were documenting cases of resistance to carbapenems, often referred to as our “antibiotic of last resort.” Yikes.

Now I know, I sound like I’m predicting the onset of Armageddon or something. And while this is a global crisis and should be taken seriously, rest assured that there are steps YOU can take to help combat the problem. There are also a lot of labs looking into alternative treatments for bacterial infections, such as bacteriophage therapy. Don’t hesitate to educate yourself on how to get involved.

So, is this a problem? Yes. Is it kind of scary? For sure. But can we figure out the solution? Definitely. For now, stay tuned and stay healthy…and please don’t take antibiotics when you have a cold.

-Jenna

Understanding and dealing with the problem of antibiotic resistance will require us to stop overperscribing antibiotics, and look to other avenues for treatment of bacterial infections. Photo credit: Haley Lawrence

Understanding and dealing with the problem of antibiotic resistance will require us to stop overperscribing antibiotics, and look to other avenues for treatment of bacterial infections. Photo credit: Haley Lawrence


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