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A diagram of the four-step killing mechanism of the polymer against drug-resistant superbugs (Step 1) Binding of the positively charged polymer to the bacteria cell surface, (Step 2) Neutralising the positive charges of the polymer to enter the bacterial cell membrane, (Step 3) Penetrating into the bacterial cyotoplasm, a fluid that fills the cell, and (Step 4) Precipitating the cytoplasmic substances to kill the bacterium/ Credit: A*STAR

A diagram of the four-step killing mechanism of the polymer against drug-resistant superbugs (Step 1) Binding of the positively charged polymer to the bacteria cell surface, (Step 2) Neutralising the positive charges of the polymer to enter the bacterial cell membrane, (Step 3) Penetrating into the bacterial cyotoplasm, a fluid that fills the cell, and (Step 4) Precipitating the cytoplasmic substances to kill the bacterium/ Credit: A*STAR

International research team develops polymer that can kill 5 types of drug-resistant bacteria

According a press release from the Agency for Science, Technology and Research (A*STAR), an international research team led by A*STAR’s Institute of Bioengineering and Nanotechnology (IBN) and IBM Research has developed a synthetic molecule that can kill five deadly types of multidrug-resistant bacteria with limited, if any, side effects. 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. 

The new material could be developed into an antimicrobial drug to treat patients with antibiotic-resistant infections. This finding was reported in the scientific journal Nature Communications.

Bacteria resistance to antibiotics presents a serious global health threat. Bacteria are beginning to develop resistance to the last-line antibiotics, which are given only to patients infected with bacteria resistant to available antibiotics.

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.

The alternatives to antibiotics being explored by the research includes synthetic polymers. However, the antimicrobial polymers developed so far are either too toxic for clinical use, not biodegradable or can only target one type of bacteria. 

To address this problem, Dr Yi Yan Yang from IBN brought together a multidisciplinary research team from the US, China and Singapore to develop a new class of antimicrobial polymers called guanidinium-functionalized polycarbonates.

They feature a unique killing mechanism that can target a broad range of multidrug-resistant bacteria. It is biodegradable and non-toxic to human cells. 

The polymer binds specifically to the bacterial cell and is then transported across the bacterial cell membrane into the cytoplasm, where it causes precipitation of the cell contents (proteins and genes), resulting in cell death. 

The team tested the polymers on mice infected with five hard-to-treat multidrug-resistant bacteria: Acinetobacter baumanniiEscherichia coliKlebsiella pneumoniaemethicillin-resistant Staphylococcus aureu and Pseudomonas aeruginosa. These superbugs commonly infect patients in the hospitals and can cause systemic infections that lead to septic shock and multiple organ failure. The results demonstrated that the bacteria were effectively removed from the mice and no toxicity was observed. 

The researchers further tested the effectiveness of the polymers on mice with two types of systemic 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.  

To determine whether the bacteria will 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.   

Dr Yi Yan Yang, Group Leader at IBN said, “We have demonstrated the first example of a biodegradable synthetic macromolecule with broad-spectrum antimicrobial activity in mice, unique killing mechanism and no toxicity. 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.” 

“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,” said Dr James Hedrick, Distinguished Research Staff Member, IBM Research – Almaden, San Jose, California. “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,” he added.

IBN and IBM are now seeking collaborations with pharmaceutical companies to develop the polymers into an antimicrobial treatment for patients.

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