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New molecule kills drug-resistant bacteria

The Straits Times

An international research team has developed a synthetic molecule that can kill five deadly types of multidrug-resistant bacteria with limited side effects, if any.

The hope is that the new material could be developed into a drug to treat patients with antibiotic-resistant infections.

The team was led by the Institute of Bioengineering and Nanotechnology (IBN) of the Agency for Science, Technology and Research (A*Star) and IBM Research.

Their findings were reported in the scientific journal Nature Communications.

Superbugs that are resistant to antibiotics are a serious health threat, said the institute in a statement.

According to the UK Review on Antimicrobial Resistance, superbugs kill around 700,000 people worldwide each year.

By 2050, 10 million people could die each year if existing antibiotics continue to lose their effectiveness.

"There is an urgent global need for new antimicrobials that are effective against superbugs," said Professor Jackie Ying, IBN's executive director.

"The situation has become more acute because bacteria are starting to develop resistance to the last-line antibiotics."

The research community is trying to develop alternatives to antibiotics using synthetic polymers.

However, the antimicrobial polymers developed so far are either too toxic for clinical use, are not biodegradable or can target only one type of bacteria, said the institute.

To address this problem, Dr Yang Yi Yan, group leader at IBN, brought together a multidisciplinary research team from the United States, China and Singapore to develop a new class of antimicrobial polymers called "guanidinium-functionalised polycarbonates" with a unique killing mechanism that can target a broad range of multidrug-resistant bacteria.

They are biodegradable and non-toxic to human cells.

The polymer kills bacteria by binding specifically to the bacterial cell, where it causes cell death.

The team tested the polymers on mice infected with five hard-to-treat multidrug-resistant bacteria: Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

These superbugs are commonly acquired by patients in hospitals and can cause infections that lead to septic shock and multiple organ failure, said IBN. The results showed that the bacteria were removed effectively from the mice and no toxicity was observed.

The researchers also tested the effectiveness of the polymers on mice with two types of infections caused by superbugs: peritonitis (an infection of the stomach's inner lining) and lung infections from Pseudomonas aeruginosa.

The polymers eliminated the bacterial infections in both groups of mice with negligible toxicity.

  • 700,000

    Number of people killed worldwide by superbugs yearly.

    10m

    Number of people who could die by 2050, if existing antibiotics continue to lose their effectiveness.

Said Dr Yang: "Once the polymer finishes its job of killing the bacteria, it will be naturally degraded after three days and will not remain in the body. This antimicrobial agent shows great promise for the treatment and prevention of multidrug-resistant systemic infections."

Said Dr James Hedrick, distinguished research staff member of IBM Research - Almaden in California: "This study illustrates the potential for this new research field we denote as 'macromolecular therapeutics' to create entirely new classes of treatments for multiple diseases.

"In 2016, we demonstrated the efficacy of synthetic polymers to combat deadly viral diseases.

"The current research for treating bacterial infections rounds out our ability to someday treat a spectrum of infectious diseases with a single, new type of mechanism without the onset of resistance."

To determine whether the bacteria would develop any resistance to the polymer, the team collaborated with Dr Paola Florez de Sessions at A*Star's Genome Institute of Singapore and the Cell Engineering group of Dr Simone Bianco at IBM Research - Almaden to perform genomic analysis.

They found that the bacteria did not show any resistance development even after multiple treatments with the polymer.

This study was also done in collaboration with the University of North Dakota's School of Medicine and Health Sciences, and the First Affiliated Hospital of Zhejiang University's College of Medicine. IBN and IBM are now hoping to work with pharmaceutical companies to develop the polymers into an antimicrobial treatment for patients.