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 Organization (WHO).
Last year, the WHO estimated that drug-resistance diseases already killed 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 organizations 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 organized 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” antibiotics, 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.
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 mean 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.”