Bugs vs. bugs


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<!--intro-->A sap-sucking insect may hold the key to a whole new class of antibacterial drugs, say scientists who have been looking at how these creatures combat infection.

Instead of antibodies, insects use small peptide molecules to fight off bacteria. Most of these work by punching a hole in the wall of bacterial cells, but this means they are often toxic to mammalian cells as well, so they wouldn't be suitable for use as drugs in humans.<!--/intro-->

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Now Laszlo Otvos from the Wistar Institute in Philadelphia and his colleagues have isolated a group of insect peptides which target specific molecules inside bacterial cells.

The peptide, present in the European sap-sucking insect Pyrrhocoris apterus, is called pyrrhocoricin. The researchers identified the protein it targets by attaching the peptide to a "hook" molecule called biotin. They mixed the biotin-peptide with bacterial cells, then used beads coated with an antibody against biotin to pull it back out of the cells again, this time bound to its mystery target.

The research will appear in the next issue of Biochemistry. "It's a very elegant piece of biochemistry," says Ian Chopra, head of the Antimicrobial Research Centre at Leeds University.

The target turned out to be a "heat shock protein" called DnaK, which re-folds malformed proteins back into shape. DnaK is an essential protein in the cell, and when it is inactivated by the peptide, the bacterium dies. All species have their own version of DnaK, but the researchers showed that the human equivalent, called Hsp70, is different enough not to be affected by the peptides--so insect DnaKs could be safe to use as drugs.

The team infected mice with different species of bacteria, and found that pyrrhocoricin protected the animals from bacteria such as Escherichia coli and Salmonella. Because DnaK has a slightly different structure in every bacterial species, each peptide is only active against a narrow range of pathogens. So by tailoring artificial peptides to match different DnaK structures, the researchers hope they will be able to modify the peptide to create a range of drugs "to order" against any type of bacterium.

Otvos says targeted drugs will help prevent the spread of antibiotic resistance because each drug will challenge fewer bacteria. Drugs specific to dangerous pathogens could be saved for use when conventional treatments fail.

"That is the ideal objective in the long term," agrees Chopra. But he says that in practice, doctors don't like using "narrow-spectrum" antibiotics because they can't always be certain which bacterium is causing an infection. "Specific antibiotics would help in the fight against resistance, but the approach would need to go hand in hand with much more rapid and improved diagnostic methods," he says.

Otvos says the technique needn't stop at antibacterial drugs. All species, from bacteria to mammals, have a version of DnaK in their cells. "These peptides are very powerful," he says. "In the long run, you could use them to combat anything, even insects or rodents."

Joanna Marchant

From New Scientist magazine, 04 November 2000.