Fighting antibiotic resistance

The war against antibiotic resistance requires a conceptual revision, namely design and creation of new types of degradable antibiotics with novel intracellular interactions, says Nobel Prize in Chemistry (2009) laureate Ada Yonath.

Antibiotic resistance is one of the greatest threats to human health, according to no less than the World Health Organisation (WHO).

Last year, the WHO estimated that drug-resistance diseases already kill more than 700,000 people annually, and this could rise to 10 million people by 2050.

The World Bank has also projected that inaction on the issue could cost the world’s economy up to 3.8 percent of its gross domestic product by that year.

To prevent this dismal future, governments and organisations need to invest in the research and the production of antibiotics that are radically different from those on the market, says Nobel laureate Ada Yonath.

Professor Yonath won the 2009 Nobel Prize in Chemistry for her work in determining the structure and function of the bacterial ribosome, which is a major target for antibiotics.

The next generation of antibiotics must be species-specific, target new sites and interactions within bacteria, and be degradable, she said in an interview ahead of the Global Young Scientists Summit 2020, where she will be a speaker.

The annual event, to be held in Singapore from Jan 14 to 17, is organised by the National Research Foundation to connect young researchers and eminent scientists to spark new ideas and conversations.

The future of antibiotics

Currently, the most widely-used antibiotics are known as “broad-spectrum” antibiotcs, namely those that tackle multiple diseases. The frequent use of such antibiotics, however, is one of the leading causes of antibiotic resistance.

Future antibiotics need to be tailored to specific species of bacteria. This will reduce the use of each antibiotic and limit the rise of antibiotic resistance, said Prof Yonath.

These new antibiotics should also work by disrupting sites and interactions within bacteria that are not the focus of existing antibiotics, as this will improve their effectiveness and delay the bacteria becoming resistant to them, she added.

Prof Yonath, who is the Martin S. and Helen Kimmel Professor of Structural Biology at the Weizmann Institute of Science in Israel, is working on identifying such new points of attack.

She has studied the structures of ribosomes – tiny factories in cells that translate the genetic code into proteins – in all cells, including both harmful and harmless bacteria.

By comparing the structures, she has singled out 25 unique sites in a model bacterium, that could be targets for new antibiotics.

Her research group is still not working with a pharmaceutical company, although such collaboration could lead to the development of a selective treatment against antibiotic-resistant strains of the Staphylococcus aureus bacteria, which is one of the most common causes of infection, especially in hospitals.

Preferably, the new antibiotics should be degradable, she said.

She explained: “Most antibiotics that are currently used are made up of small, toxic, organic molecules that cannot be digested and are therefore expelled into the environment.

“They are so small that most purification facilities cannot catch them, so they penetrate sewerage systems and eventually come back to us.”

In 2019, scientists found that many rivers worldwide are polluted with antibiotics that exceed recommended environmental safety thresholds by up to 300 times.

One or more common antibiotics were found in two-thirds of the 711 samples taken from rivers in 72 countries, where they could contribute to bacteria becoming resistant to them.

Making antibiotics degradable could help to curtail this problem.

Beyond antibiotics

Blunting the impact of antibiotic resistance, however, will require more than just new types of antibiotics.

“To make species-specific antibiotics viable, doctors must be able to quickly and correctly identify the bacteria causing the disease so that they can prescribe the right antibiotic,” said Prof Yonath.

This means that they need more sophisticated diagnostic tools and techniques. In fact, speeding up of the procedures for the identification of the actual clinical pathogen is currently undergoing by a few pharma companies.

Furthermore, the best way to restrict the emergence of antibiotic resistance is to use fewer antibiotics in the first place. “Healthier lives means lesser use of antibiotics,” she said.

The WHO recommends taking actions such as regularly washing hands, preparing food hygienically, practicing safer sex and having up-to-date vaccinations, to prevent infections.

In Singapore, the Health Promotion Board (HPB) has also run campaigns to promote awareness of the right use of antibiotics.

For example, antibiotics only work for bacterial infections, and are ineffective against common coughs, colds and sore throats, which are usually caused by viruses. Patients also should not ask for antibiotics if their doctors do not prescribe it, the HPB has said.

“We’re unlikely to completely eradicate antibiotic resistance, because bacteria want to live, and they are cleverer than us,” said Prof Yonath. “But there is much more that we can do to contain it and reduce its impact on human health.”


About Ada Yonath
Nobel Prize in Chemistry 2009

All cells in living organisms contain tiny factories called ribosomes. These translate the genetic code into proteins, which are essential to life. They act in the same fashion in all living cells, whether in bacteria or in elephants. In humans, ribosomes produce proteins that transport oxygen, capture viruses, create energy and carry out many other tasks.

In the late 1970s, Professor Ada Yonath turned her attention to these minuscule wonders and, against all odds, eventually succeeded in determining the structure of the bacterial ribosome, a breakthrough that shed light on how all ribosomes function.

Since the ribosome is a major bacterial target for antibiotics, her discoveries have also led to the design of new innovative, eco-friendly and pathogen-specific antibiotics, and to a better understanding of antibiotic resistance, which the World Health Organisation calls one of the biggest threats to global health.

For her seminal work, Professor Yonath was awarded the 2009 Nobel Prize in Chemistry alongside two other scientists. The Nobel Prize committee noted that when Professor Yonath began her research, the ribosome was considered impossible to crystallise - a key step to determining its structure - because of its size, lack of internal symmetry and instability.

Despite steep odds and widespread derision, she persevered. She overcame the instability problem by using ribosomes from tough bacterial strains found in the Dead Sea, hot springs and nuclear facilities’ waste, and after 25,000 searches for the right crystallization conditions, succeeded in obtaining ribosomal crystals.

The crystals, however, decayed almost instantly at ambient temperature in X-rays used for data collection. Professor Yonath thought the cause was motion within the sensitive crystals, and invented a way to minimise their internal energy and reduce the motion by deep cooling.

To avoid ice formation within and around the crystals, she dipped them in a high viscosity hydrocarbon polymer before snap-freezing them to cryogenic temperatures. This technique is now called cryo-bio-crystallography and is routinely used in structural biology.

Due to her innovations, others tried to determine the ribosome’s structure. In 2000, she and her fellow Nobel Laureates were the first with almost simultaneously published papers.

Professor Yonath is the Martin S. and Helen Kimmel Professor of Structural Biology at the Weizmann Institute of Science in Israel, where she is working on the translation of the genetic code, antibiotics that hamper it, antibiotic resistance issues, and the origin of life.



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