A bee delivers both sting and a dose of melittin, the active component in its venom.

Poking holes for good and bad

The active ingredient in bee venom is melittin, a peptide that does its damage by increasing the permeability of cell membranes to ions. In other words, it pokes holes in cells, allowing their contents to leak out.

In small doses, the pore-inducing effects of melittin are temporary. The holes close up. But recent research out of Rice University suggests that at higher concentrations, the pores stabilize and stay open. And at even greater exposures, melittin can cause cell membranes to dissolve altogether.

So add melittin to the list of candidates for a new class of drugs intended to attack and kill bacteria, cancer cells and other targets by lethal puncture. Such drugs don’t exist yet, but their attractiveness is undeniable.

“This strategy of opening holes in the cell membrane is employed by a great number of host-defense antimicrobial peptides, many of which have been discovered over the past 30 years,” says Huey Huang, lead investigator of the Rice study.

“People are interested in using these peptides to fight cancer and other diseases, in part because organisms cannot change the makeup of their membrane, so it would be very difficult for them to develop resistance to such drugs.”

One major hurdle has been figuring out exactly how melittin and similar peptides work. The Rice researchers provide some clues. They created synthetic membrane-enclosed structures similar in size to living cells (dubbed giant unilamellar vesicles or GUVs), filled them with dye, immersed them in solution containing melittin and then filmed the action with time-lapse video.

The peptide, which was labeled with a green fluorescent protein, almost immediately began sticking to GUVs. Within two minutes, so much melittin bound to the outer membrane of the GUVs that their surfaces began to change to accommodate the load. Openings formed and dye began to leak out.

The Rice research advances similar work on-going in lots of places. For example, researchers at Washington University in St. Louis reported earlier this year using nanoparticles filled with bee venom to kill human HIV cells without harming surrounding cells.

Naturally, there’s a flip side to all of this therapeutic experimentation. Toxins like melittin pose an inherent health risk as well. Think MRSA, E. coli and snake venom. They all cause harm by poking holes in cell membranes.

So there’s also a need for a way to sop up these toxins before much damage is done.

Researchers at the UC San Diego Jacobs School of Engineering have created nanosponges capable of removing toxins from the bloodstream. Unlike other anti-toxin platforms that must be custom synthesized to individual toxin types, these sponges absorb a broad class of toxins. You can read more here.

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This movie shows the top view of a melittin (venom from honey bees) tetramer embedded in a POPE lipid bilayer. 

Researchers at the Washington university of medicine have found that the hiv virus cell can be destroyed by nanoparticles laced with metillin, a bee venom. Metillin destroys the double membrane protective later of the hiv virus but since human cells are not double membraned (or so i gather from the article) metillin fits not kill living cells.

I’m amazed by how simple the solution sounds. I’m also amazed that bee venom is what it might take to kill HIV. How lateral is that!

Oh, by the way, it’s a research funded by the Bill and Melinda Gates Foundation.

Found the story on reddit’s frontpage.

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Showcase: the antimicrobial peptide, melittin (from honey bee toxin) interacting with PC phosphlipids.

Khalid & Berglund (unpublished)

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