Random Scrambled Polymers Kill Drug-Resistant Bacteria

Via newscientist.com -

Scrambled-up" polymers can kill bacteria, and may offer hope in beating problems of antibiotic drug resistance, suggests a new study.

Researchers at the University of Wisconsin, in Madison, US, had been working on making molecules that mimic the short proteins known as "host-defence peptides".

They are produced as part of the innate immune response by all kinds of organisms – from plants to humans – to kill bacteria, and work, most researchers believe, by sticking onto bacteria's membranes and opening holes in them.

To mimic these natural defences, the researchers, led by Samuel Gellman and Shannon Stahl were building polymers by stringing together certain sub-units, called beta-lactams, in a particular order.

As a control for their experiments, they also assembled scrambled polymers with the sub-units in random order.

Control killer
But to their surprise, the random polymers were better at killing bacteria, Gellman says. And compared with both the ordered polymers and the natural host-defence peptides, the random polymers killed many fewer red blood cells – a crude measure of their potential toxicity to humans.

Relatively low doses of the random polymers were able to kill drug-resistant bacteria, such as Staphylococcus aureus, which is resistant to the powerful antibiotic vancomycin.

The random polymers were effective against more bacteria, and less toxic to red blood cells, than three widely tested natural host-defence peptides, the study showed. "Our study is the first to show you can get polymers that match the selectivity of natural host-defence peptides," Gellman says.

The polymers seem to be attracted to bacteria's negatively charged membranes, where the polymers reshape themselves and punch holes in the membrane. Animal cells, on the other hand, are generally neutrally charged, so the polymers are much less attracted to them. "I'm really excited about this work," Gellman says, because it could provide a cheap way of producing a new class of antibiotics.

And the polymers should likewise remain effective for a long time, Gellman argues, since bacteria have a hard time evolving resistance to natural host-defence peptides. This is because the peptides attack a fundamental part of the cell, the membrane, using a basic physical interaction rather than targeting a specific part of the cellular machinery inside, as man-made antibiotics typically do.

"It seems when they add randomness, they get away from the toxicity," says Robert Hancock of the University of British Columbia in Vancouver, Canada.

But he cautions that it may be difficult to get regulatory approval from the US Food and Drug Administration for the polymers, since they are mixtures of different molecules, which may each have different effects, and would therefore each need separate safety tests.

Michael Zasloff of Georgetown University in Washington, DC, US, says he is surprised at how well the random polymers work. "I would have expected that they were indiscriminately destructive, rather than exhibiting the specificity they do." If they pan out in animal studies, it "will most certainly lead to human studies," Zasloff says.

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This is exactly why I love science. The random control ended up being more valuable than the orderly "host-defence peptide" mimicking polymer - at least in this study. This result could lead to another study, focusing on the ability of the random polymers to kill so effectively.

Scientific method at its best....