Polymers that can be fine-tuned for optimal effect could help fight multidrug-resistant infections

Jul 02, 2014
Polymers that can be fine-tuned for optimal effect could help fight multidrug-resistant infections
Scanning electron microscopy images of Escherichia coli before (top) and after (bottom) two-hour treatment with a polymer. The treated E. coli cells show distorted and corrugated surfaces compared to the intact control cells. Credit: American Chemical Society

The rise of drug-resistant microbes is a major challenge facing medicine. The World Health Organization's 2014 report on global surveillance of antimicrobial resistance warns of the very real possibility of the twenty-first century becoming "a post-antibiotic era—in which common infections and minor injuries can kill". In the face of this threat, researchers worldwide are exploring approaches to find new compounds that combine selective antimicrobial efficacy with low toxicity toward mammalian cells.

Yi Yan Yang at the A*STAR Institute of Bioengineering and Nanotechnology in Singapore and co-workers have now created a range of large polycarbonate molecules that are potent antimicrobials and are tolerated well by rat , suggesting that they could prove similarly effective in humans. Crucially, by subtly varying the composition of the polycarbonate molecules, the researchers could fine-tune the selectivity and activity of these candidate drugs.

Antimicrobial polycarbonates are long-chain polymers made by linking small monomer molecules. Each monomer contains two components: one that is hydrophobic and physically inserts into the cell membrane of bacteria and fungi; and one that carries a positively charged group that is attracted to the negative charge on the surface of .

By carefully tinkering with the hydrophobic and hydrophilic balance between the components of these new monomers, the researchers were able to create polymers that adhere to microbial cells and disrupt their cell membranes, thereby killing the cells (see image).

The polycarbonates developed by the researchers have proven highly effective against a variety of clinically isolated multidrug-resistant bacteria and fungi. A further benefit is that the molecules are biodegradable, which means that, when used in clinical situations, they should take effect and then degrade naturally. This attribute provides a crucial advantage over other synthetic alternatives that persist and cause undesirable side effects.

Using scanning electron microscopy, the researchers showed that the molecules work by breaking open the microbial —a mode of action they believe reduces the likelihood of microbes becoming resistant to the polycarbonates.

The ability to explore different compositions within the monomers may allow further enhancements, according to the researchers. "By carefully controlling the structure and the ratio of the two components, we can enhance dramatically the selectivity of the polymers toward a broad range of pathogenic microbes," says Yang. The researchers will now study the in vivo efficacy of the optimal polymer using intravenous injection into mice infected with methicillin-resistant Staphylococcus aureus (MRSA) bacteria that have developed resistance to a broad class of antibiotics.

Explore further: Cationic small molecules hold great potential for preventing and treating fungal infections

More information: Chin, W., Yang, C, Ng, V. W. L., Huang, Y., Cheng, J. et al. "Biodegradable broad-spectrum antimicrobial polycarbonates: Investigating the role of chemical structure on activity and selectivity." Macromolecules 46, 8797–8807 (2013). dx.doi.org/10.1021/ma4019685

add to favorites email to friend print save as pdf

Related Stories

Pushing back against drug-resistant bugs

Jan 22, 2014

Some pathogens can adapt to the presence of drugs that would normally be lethal, and such antibiotic-resistant microbes are now the scourge of hospitals worldwide. Discovering new antibiotics is a laborious ...

Recommended for you

Oat breakfast cereals may contain a common mold-related toxin

Feb 25, 2015

Oats are often touted for boosting heart health, but scientists warn that the grain and its products might need closer monitoring for potential mold contamination. They report in ACS' Journal of Agricultural and Food Chemistry that s ...

NETL invents improved oxygen carriers

Feb 24, 2015

One of the keys to the successful deployment of chemical looping technologies is the development of affordable, high performance oxygen carriers. One potential solution is the naturally-occurring iron oxide, ...

Research could make blue jeans green

Feb 23, 2015

Who doesn't like blue jeans? They're practically wrinkle-proof. The indigo dye that provides their distinctive color holds up to detergents, but ages into that soft, worn look. No wonder the average American ...

Novel electrode boosts green hydrogen research

Feb 20, 2015

Scientists from the National Physical Laboratory (NPL) have developed a novel reference electrode, and are working with hydrogen energy system manufacturer ITM Power to aid the development of hydrogen production ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.