A synthetic molecule that can kill five deadly types of multidrug-resistant bacteria with limited, if any, side effects, has been developed. The material engineered by researchers from the Institute of Bioengineering and Nanotechnology (IBN) of the Agency for Science, Technology and Research (A*STAR) and IBM Research could be developed into an antimicrobial drug to treat patients with antibiotic-resistant infections.

Such antibiotic-resistant superbugs kill around 700,000 people annually worldwide, according to the UK Normal cells of the Acinetobacter baumannii bacteria before (left) and after (right) treatment with the polymers. Source: Agency for Science, Technology and Research (A*STAR), Singapore Normal cells of the Acinetobacter baumannii bacteria before (left) and after (right) treatment with the polymers. Source: Agency for Science, Technology and Research (A*STAR), Singapore Review on Antimicrobial Resistance. By 2050, 10 million people could die each year if existing antibiotics continue to lose their effectiveness.

The biomedical research community is trying to develop alternatives to antibiotics using synthetic polymers, but antimicrobial polymers developed to date are either too toxic for clinical use, not biodegradable or can only target one type of bacteria.

The newly developed class of antimicrobial polymers -- called guanidinium-functionalized polycarbonates – is armed with a unique killing mechanism that can target a broad range of multidrug-resistant bacteria. It is also biodegradable and non-toxic to human cells.

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

Tests were conducted on mice infected with five hard-to-treat multidrug-resistant bacteria: Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureu and Pseudomonas aeruginosa. These superbugs are commonly acquired by patients in the 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.

Additional trials were performed on mice with two types of systemic infections caused by superbugs: peritonitis and lung infections from Pseudomonas aeruginosa. The polymers eliminated the bacterial infections in both groups of mice with negligible toxicity.

Genomic analyses demonstrated that the bacteria did not show any resistance development even after multiple treatments with the polymer.

The research is published in the journal Nature Communications.

To contact the author of this article, email shimmelstein@globalspec.com