How Humanity’s Use of Antibiotics Is Engineering the Perfect Superbug

It’s time to take steps to avoid the antibiotic apocalypse

Photo: zhangshuang/Getty Images

Five years ago, researchers at Harvard Medical School released a video of an experiment, revealing how easy it is for bacteria to become resistant to antibiotics.

The team constructed a large petri dish for growing bacteria and separated it into distinct bands. Across the dish, the bands contained progressively higher concentrations of antibiotic, from 0 to 1,000 times the concentration that bacteria can normally tolerate. Then they grew bacteria, starting in the band with no antibiotics.

Photo: Kishony Lab/Harvard Medical School and Technion

Over time, the bacteria grew and spread across the different bands. At the border of each new band, growth paused until antibiotic-resistant mutants emerged and continued spreading across the plate. After only 10 days, the bacteria had become completely resistant to antibiotics at 1,000x concentration due to successive mutations that allowed the bacteria to develop antibiotic resistance.

Photo: Kishony Lab/Harvard Medical School and Technion

This experiment demonstrated the frightening ability for bacteria to accumulate successive mutations and “evolve resistance to extremely high concentrations of antibiotics in a short period of time”.

In the future, routine medical procedures such as surgery and chemotherapy may become too dangerous to perform if our antibiotics are no longer effective. If a highly infectious bacterium evolves into a superbug, we may have another pandemic on our hands.

Scientists, have been warning the public for years about this problem. In 2016, before she became the director of the U.S. Centers for Disease Control and Prevention, Rochelle Walensky, MD cautioned that “if we use antibiotics when not needed, we may not have them when they are most needed.”

You thought Covid-19 was bad? A superbug pandemic could be far worse.

Pathogenic bacteria are found almost everywhere. Usually, the immune system is capable of defending against invading bacteria, but in cases of particularly bad infections, antibiotics are used to help fend off the attack by killing bacteria or slowing their growth.

Antibiotics have revolutionized medicine, but now they are being misused at an ever increasing rate, both in humans and in animals. A paper published in 2018 found that the consumption of antibiotics rose by 65% between 2000 and 2015. According to a 2009 report from the Food and Drug Administration, nearly 13 million kilograms of antibiotics are used for livestock in a single year.

Using enormous volumes of antibiotics greatly increases the exposure of bacteria to these drugs, providing them the opportunity to develop resistance and evolve into the perfect “superbugs”: bacteria that are resistant to every form of treatment.

Photo: CDC/Wikimedia Commons

How do antibiotics work?

Bacteria cause disease by releasing toxins into the body, damaging cells and disrupting normal function. Particularly dangerous infections occur when the bacteria reproduce rapidly and overwhelm immune defenses. Antibiotics are used to slow down the infection and buy time for the immune system to fully activate.

Antibiotics affect bacteria in two main ways: impairing DNA replication and puncturing the cell wall. For bacteria to reproduce, they must first replicate their DNA. Some antibiotics introduce irreparable damage into the bacteria’s DNA and hinder its ability to replicate. This causes the bacteria to enter a state of stasis, greatly minimizing its potential effect on the body.

Further, bacterial cell walls are enclosed in a polymer called peptidoglycan. This polymer isn’t present in human cells, making it a prime target for antibiotics. Antibiotics inhibit the production of this polymer and break down its bonds, puncturing the cell wall and leading to the death of the bacteria.

Photo: Gabriel Vergani/Getty Images

How are bacteria evolving into superbugs?

Every time a bacterium replicates, its DNA mutates. While most mutations don’t have an effect on the organism, some are beneficial and confer some sort of survival advantage, such as immunity to antibiotics. Some bacteria can replicate in 30 minutes under ideal conditions, allowing a single cell to grow into a colony of millions in just 24 hours. A lot of random genetic mutations can occur during this period.

According to Darwin’s law of natural selection, beneficial mutations are selected for and propagate throughout a population over time. Bacteria naturally have genetic variation because random mutations occur when they divide. A change in the environment — like the use of antibiotics — places a selective pressure on the population. This means that those with mutations for antibiotic resistance will be more likely to survive and reproduce, and in time, they will become the dominant strain. Eventually, the whole colony will adapt to the antibiotics and become resistant.

Increasing the potential for resistance, bacteria can also share genes via plasmids — small circular pieces of DNA. Much how we can visit a program’s website and download the latest security update, bacteria talk to each other via a process called conjugation and share plasmids that contain antibiotic resistance genes with each other.

These phenomena are exactly what the scientists at Harvard Medical School saw. Bacterial growth would pause at each new band, where the level of antibiotic was too toxic, until one strain developed immunity. Then, as the mutations were passed around, the floodgates opened as the rest of the bacterial population quickly gained immunity and crossed the threshold.

What needs to be done?

Unfortunately, antibiotic resistance is already occurring and is plaguing hospitals around the world. Resistant infections are the third-leading cause of death, according to a paper published in the journal Nature Medicine this year. For example, one bacterial strain known as MRSA (short for methicillin-resistant Staphylococcus aureus) can cause severe respiratory infections, resulting in 120,000 infections in the United States each year.

But we can still work together to fix this problem and avoid the antibiotic apocalypse. Here’s how:

Control use of antibiotics. Antibiotics need to be used sparingly. The CDC estimates that one in three antibiotic prescriptions are unnecessary, with some doctors prescribing them for viral infections when they know that antibiotics have no effect on viruses.

Incentivize research and development for new antibiotics. Since the 1980s, the discovery of new antibiotics has slowed to a standstill. Pharmaceutical companies have lost interest in looking for developing novel antibiotics as they are almost always only able to be used for a narrow range of bacteria, reducing profits. Further, antibiotic prescriptions are temporary, meaning that they do not have a consistent source of revenue. For these reasons, pharmaceutical companies have invested more time and money into looking for drugs that are taken over a long period of time, such as blood pressure medication and antidepressants. Incentivizing research into developing new antibiotics is critical if we want to develop better treatments.

You. It is important to only use antibiotics when prescribed, and not to use any leftover dosages. Additionally, when prescribed antibiotics, it is imperative to finish the full course — while you might be feeling better, you are not necessarily better. There may be some latent bacteria left over that could develop resistance if you do not complete the full course and finish them off.

Photo: fpm/Getty Images

Scientists are well aware of the antibiotic crisis and are working hard to fight against resistant bacteria. Bacteriophages, one promising tool, are bacteria’s natural predator, capable of physically puncturing bacteria cell walls and inducing cell death. These phages only attack one type of bacteria at a time, meaning they can be used as a highly precise medical tool to fight against specific antibiotic-resistant strains. While this therapy hasn’t been popularized yet — antibiotics are still easier and cheaper to prepare — it is nonetheless reassuring to know that researchers are developing methods to fight against antibiotic resistance.

Aspiring physician-scientist. Currently studying B.E. Biomedical Engineering (Honours) and B.S. Computer Science.

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