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鈥檛
be suitable for use as drugs in humans.
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.
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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 鈥渉ook鈥� 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. 鈥淚t鈥檚 a
very elegant piece of biochemistry,鈥� says Ian Chopra, head of the Antimicrobial
Research Centre at Leeds University.
The target turned out to be a 鈥渉eat shock protein鈥� 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鈥攕o 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 鈥渢o order鈥� 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.
鈥淭hat is the ideal objective in the long term,鈥� agrees Chopra. But he says
that in practice, doctors don鈥檛 like using 鈥渘arrow-spectrum鈥� antibiotics because
they can鈥檛 always be certain which bacterium is causing an infection. 鈥淪pecific
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,鈥�
he says.
Otvos says the technique needn鈥檛 stop at antibacterial drugs. All species,
from bacteria to mammals, have a version of DnaK in their cells. 鈥淭hese peptides
are very powerful,鈥� he says. 鈥淚n the long run, you could use them to combat
anything, even insects or rodents.鈥�