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A new synthetic material can kill five multi-drug resistant superbugs

Photo Credit: a-star.edu.sg
Superbugs resistant to antibiotics kill around 70,000 worldwide
by TR Pakistan

An international research team has developed a synthetic molecule that can kill five deadly types of multidrug-resistant bacteria with limited, if any, side effects, says a statement issued by Singapore-based Agency for Science, Technology, and Research (A*STAR).

The new material can be developed into an antimicrobial drug to treat patients with antibiotic-resistant infections.

“Superbugs that are resistant to antibiotics are a serious health threat. 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 statement says.

“The research community has been trying to develop alternatives to antibiotics using 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.”

Read more: Pakistani researchers get patents for nano-antibiotics

To address this problem, Dr Yi Yan Yang from A*STAR’s Institute of Bioengineering and Nanotechnology (IBN) and his multidisciplinary team of researchers from the US, China, and Singapore have developed a new class of antimicrobial polymers called guanidinium-functionalized polycarbonates with a unique killing mechanism that can target a broad range of multidrug-resistant bacteria. The material is biodegradable and non-toxic to human cells.

“The polymer kills bacteria in the following way. First, the polymer binds specifically to the bacterial cell. Then, it is transported across the bacterial cell membrane into the cytoplasm, where it causes precipitation of the cell contents (proteins and genes), resulting in cell death,” Dr Yang says.

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) Neutralizing 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. Photo Credit: a-star.edu.sg

The team has tested the polymers on mice infected with five hard-to-treat multidrug-resistant bacteria: Acinetobacterbaumannii, Escherichia coli, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureu, and Pseudomonas aeruginosa. “These superbugs are commonly acquired by patients in hospitals and can cause systemic infections that lead to septic shock and multiple organ failure. The results showed 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.

“Once the polymer finishes its job of killing the bacteria, it naturally degrades after three days and does not remain in the body. This antimicrobial agent shows great promise for the treatment and prevention of multidrug-resistant systemic infections,” Dr Yang further further says.

“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,” says Dr James Hedrick, a distinguished research staff member at IBM Research, a partner in the research.

“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 adds.

To determine whether the bacteria may develop resistance to the polymer, genomic analysis was carried out jointly by Dr Paola Florez de Sessions of A*STAR’s Genome Institute of Singapore and Dr Simone Bianco of IBM’s Cell Engineering group. They found that the bacteria did not show any resistance development even after multiple treatments with the polymer.

Professor Jackie Y. Ying, the IBN executive director, has been quoted as saying that there is an urgent global need for new antimicrobials that are effective against superbugs. “The situation has become more acute because bacteria are starting to develop resistance to the last-line antibiotics, which are given only to patients infected with bacteria resistant to available antibiotics.” he notes.

The research team is now seeking collaborations with pharmaceutical companies to develop the polymers into an antimicrobial treatment for patients.

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