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Alternatives to antibiotics

Published: 25 February 2021

As bacteria become increasingly resistant to the antibiotics we have relied on for decades, how are scientists developing new treatments to fight the infections of today?

What will replace our failing antibiotics?

Antibiotics are medicines used to treat infections caused by bacteria. Some types of bacteria have evolved the ability to survive—or be resistant to—antibiotics. Scientists across the world are on an urgent hunt for new treatments to help fight infections before the antibiotics we use today become obsolete.

Researchers have found potential replacements for antibiotics in nature. The big challenge is getting these exciting discoveries out of the lab and into hospitals.

Recent improvements in biotechnology, genetic engineering and synthetic chemistry have opened new avenues of research for innovative therapies to solve our growing problem.

Where will we find new antibiotics?

Microbes such as mould, viruses, and bacteria are often stuck living next to each other, competing for resources. One of the best defences microbes have evolved is to secrete chemicals that can kill or inhibit nearby competitors. Scientists have been taking advantage of this microbe chemical warfare for the past 80 years to develop antibiotics that attack bacteria that cause disease.

Teams of scientists are on the hunt for new colonies of microbes to extract and isolate these chemicals as potential new antibiotics. Their test sites range from the bizarre to the very ordinary.

Researchers in Ireland discovered a previously unknown strain of bacteria in the soil of a graveyard which can kill MRSA—a ‘superbug’ that is resistant to several types of antibiotics. This discovery hints that there may have been some truth in the ancient myth surrounding the graveyard's mysterious healing powers.

Researchers at Liverpool School of Tropical Medicine discovered that 25% of bacteria taken from swabs of beards showed antibiotic activity. This discovery inspired them to send out swab kits, inviting people to submit samples to be tested for antimicrobial properties. Swabs from trampolines, keyboards, bank notes, the floor of a London Underground train and the inside of a public toilet have been sent back for analysis.

Scientists are also on the hunt for new microbes with antibiotic potential in much more extreme environments including thermal vents, deep fjords and secluded Icelandic marshes.

A research team in Iceland explores microenvironments in order to collect samples of sediment, sponges and seaweed

What are bacteriophages?

Model of bacteriophage T4 virus made at the Laboratory of Molecular Biology, Cambridge
Science Museum Group More information about Model of bacteriophage T4 virus made at the Laboratory of Molecular Biology, Cambridge

Bacteriophages are viruses that attack bacterial cells. They attach themselves to a susceptible bacterium and inject it with genetic material. The genetic material hijacks the bacterium and forces it to produce new bacteriophages until it explodes.

Bacteriophage cycle
Bacteriophage cycle

In many ways bacteriophages are an excellent replacement for antibiotics. They can be inhaled, injected, drank or applied directly to the skin, whatever’s best for the patient. They only interact with the disease-causing bacteria they are targeting, so don’t harm a patient’s own cells, or their ‘good’ bacteria, like in the gut.

The major downside is that each type of bacteriophage can only attack one species of bacteria. You need to know exactly what bacteria they are infected with to find the right bacteriophage. This is a time-consuming process and can mean a patient’s condition can worsen while the tests are carried out.

For the moment bacteriophage therapy is only used in one-off emergency cases. Scientists hunt for bacteriophage across the world in many environments—including sewage treatment works, kitchen sponges and even patients’ own bodies.

Phage typing machine used to determine bacteria strains present in multiple samples. London, England, 1959.
Science Museum Group Collection More information about Phage typing machine used to determine bacteria strains present in multiple samples. London, England, 1959.

Patient story: Tom Patterson

In 2015, Tom Patterson and his wife were on holiday in Egypt when Tom fell ill. He experienced abdominal pains, high fever, high heart rate and vomiting. Doctors discovered he was suffering from pancreatitis, an inflammation of the pancreas, but standard medicines had no effect.

His condition worsened and he was flown to Frankfurt for specialist treatment. There, doctors discovered Tom was infected with Acinetobacter baumannii, a deadly bacterium that is resistant to multiple antibiotics. Three antibiotics in combination showed beneficial effects but after just nine days the bacteria had become fully resistant.

Tom’s condition rapidly deteriorated and he lapsed into a coma. His wife sought emergency authorisation from the medical regulators and his doctors began an untested treatment. A cocktail of four bacteriophages were pumped through catheters into the area around his pancreas and his bloodstream.

His improvement was rapid, and he emerged from his coma within three days.

Tom and Steffanie, with illustrations of Acinetobacter and a bacteria-eating phage
Tom and Steffanie, with illustrations of Acinetobacter and a bacteria-eating phage

What is lysin?

Bacteriophages produce lysins—a protein or enzyme—to punch holes in a bacteria’s cell walls. Bacteria cells are like high-pressure balloons, so once popped their insides simply leak out, killing them.

Lysins are highly potent; microgram quantities can destroy millions of bacteria within seconds.

Instead of using whole bacteriophages, scientists are looking into a more direct approach by just using lysins to kill bacteria. A lysin produced by a group at the Rockefeller University in New York has shown encouraging results in clinical trials. It’s the first antibiotic alternative to get close to being approved for use as a licensed drug.

Naturally occurring lysins look like a promising treatment, but scientists are also working on genetically engineering lysins so they can kill more than one type of bacteria.

A transmission electron microscopy image of a Streptococcus pyogenes bacteria cell breaking open after exposure to the a lysin
A Streptococcus pyogenes bacteria cell breaks open after exposure to the lysin. Credit: Daniel Nelson, UMD

Smart antibiotics

What is Crispr-Cas9?

CRISPR-Cas9 is a defence mechanism used by bacteria to protect themselves from viruses. The bacteria capture tiny bits of DNA from attacking viruses and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to "remember" the virus and use the Cas9 mechanism to disable other viruses by cutting up the virus’s DNA.

The CRISPR-Cas9 process is now used by scientists to effectively copy and paste DNA far more accurately than they were able to before. It has sparked a revolution in genetic engineering.

How scientists use CRISPR in the lab

Scientists are in the very early stages of working on how to turn bacteria’s defence mechanism, CRISPR-Cas9, against itself as the basis for future antibiotics. These ‘smart antibiotics’ might be genetically engineered viruses programmed to attack only disease-causing bacteria.

In the far future we could even have our gut bacteria modified so they’d attack disease-causing bacteria before they get the change to make us ill.