Short-chain synthetic polymers with potent efficacy against multidrug-resistant microbes

Nov 21, 2012
Antibiotics: The plastic approach
A microbial membrane (bottom) ruptured by multiple oligomer chains. The image above is a schematic representation of the cell wall (grayish surfaces and an aqua core) breach by the oligomer chains (bolded blue, yellow, gray, orange, green and red). Credit: 2012 Institute of Bioengineering and Nanotechnology (top); Credit: 2012 Elsevier (bottom)

As pathogenic bacteria overcome our current arsenal of antibiotic drugs, new antimicrobial therapies with fresh modes of action are needed. A set of antimicrobials based on synthetic polymers is a promising approach. These experimental therapeutics are highly effective at killing multi-drug-resistant pathogenic bacterial cells, but they have a low selectivity for their target over host tissues and are toxic to red blood cells. Now, an alternative approach to polymer design that overcomes this toxicity, while retaining the high efficacy against pathogens, has been developed by a team led by Yugen Zhang at the A*STAR Institute of Bioengineering and Nanotechnology.

-based antibiotic drugs were originally inspired by produced by certain species in nature. Importantly, bacteria have proven very slow to develop resistance against these peptides, possibly owing to their particular mode of action: the peptides physically insert into an invading pathogen's cell membrane, disrupt its structure and kill the cell.

Although based on these natural peptides would be expensive to produce, polymer-based mimics should be low-cost, says Zhang. These synthetic structures copy the 'amphiphilic' structure of the natural peptides: they consist of alternating polar and non-polar subunits. The charged, polar units not only help the polymer to penetrate the pathogen's cell membrane, they can also disrupt host cells.

In a bid to tune the toxicity of the polymer drugs to avoid killing non-, Zhang and his co-workers abandoned the long-chain polymer design. They reasoned that they could improve selectivity by shortening the synthetic chain length, while retaining its highly efficient amphiphilic structure. The short-chain drugs that the researchers produced are known as oligomers.

In tests against a range of drug-resistant pathogenic bacteria and , the researchers confirmed that the amphiphilic oligomers retained their broad-spectrum killing action. Electron microscope images showed that, within a few hours of treatment, multiple oligomer strands had penetrated the pathogens' cell walls, causing them to rupture (see image). Crucially, however, even at high concentrations, these oligomers had minimal effect on .

Having demonstrated in principle that oligomers can improve target selectivity of antimicrobials based on synthetic polymers, Zhang and co-workers plan to refine the idea by further modifying the oligomers' structures. They believe this will further improve their antimicrobial properties. Other applications besides medical uses are also possible, according to Zhang. "We intend to investigate various applications of these compounds, including their potential as a preservative for cosmetics."

Explore further: Treating pain by blocking the 'chili-pepper receptor'

More information: Liu, L., Huang, Y., Riduan S. N., Gao, S., Yang, Y. et al. Main-chain imidazolium oligomer material as a selective biomimetic antimicrobial agent. Biomaterials 33, 8625–8631 (2012). dx.doi.org/10.1016/j.biomaterials.2012.08.006

add to favorites email to friend print save as pdf

Related Stories

Scientists use frogs to battle superbugs

Mar 19, 2012

(PhysOrg.com) -- Nuclear scientists using frogs in a battle against superbugs might sound like some kind of 1980s computer game – but it’s actually scientific research underway right now.

An alternative to antibiotics

Jun 08, 2011

Antibiotics are among the greatest achievements of medical science. But lately the former multi-purpose weapon fails in the battle against infectious diseases. Bacteria are increasingly developing resistance ...

Stinky frogs are a treasure trove of antibiotic substances

Nov 30, 2011

Some of the nastiest smelling creatures on Earth have skin that produces the greatest known variety of anti-bacterial substances that hold promise for becoming new weapons in the battle against antibiotic-resistant ...

Recommended for you

Treating pain by blocking the 'chili-pepper receptor'

8 hours ago

Biting into a chili pepper causes a burning spiciness that is irresistible to some, but intolerable to others. Scientists exploring the chili pepper's effect are using their findings to develop a new drug ...

Moving single cells around—accurately and cheaply

Aug 19, 2014

Scientists at the Houston Methodist Research Institute have figured out how to pick up and transfer single cells using a pipette—a common laboratory tool that's been tweaked slightly. They describe this ...

The difficult question of Clostridium difficile

Aug 19, 2014

The bacterium Clostridium difficile causes antibiotic-related diarrhoea and is a growing problem in the hospital environment and elsewhere in the community. Understanding how the microbe colonises the hu ...

User comments : 0