Tuesday, 6 March 2012

Nairobi bugs: WMD or Cancer cure?!

15 times more toxic than cobra venom, you really shouldn't eat a Nairobi beetle!
Nairobi bugs (also known around East Africa as Nairobi Eye, Nairobi Fly, Nairobi beetles, Blister Beetles and a whole range of other names) are not the best loved creatures out here. This year they've come out in greater number than the last few years, presumably thanks to some relatively good rains, and whilst they're not loved, they're certainly fascinating wee beasties. But before we go into the details, let's start with some identification preliminaries.

There are actually at least two species of beetle known as Nairobi bugs around here, but they're so similar that most people won't notice them. Similarly marked relatives of these two are pretty widely distributed across the world, mainly in the tropics, and for now I don't think we need to bother about the precise identification. They're all small (7mm-1cm ish) and well marked with typical warning (aposematic) colours of black and red. In fact, despite the variety of names these are beetles (Coleopterans) of the family Staphylinidae, the rove beetles. If you don't know the Nairobi beetle, you might well know the Devil's Coach-horse and similar species - much larger and all black, but of a similar basic structure. The beetles we're interested in are of the genus Paederus and are carnivorous beetles that live mostly in long grass and anywhere with rotting leaves. And the most interesting things about them, as anyone will tell you, is that whilst they neither bite nor sting, they're still seriously nasty.

All you have to do is brush against or slightly squash a Nairobi but, and you'll likely end up with chemical burns wherever you came in contact with the beast. It's a pretty remarkable defence (and fairly effective at dissuading the main predator - wolf spiders - from eating them too, though not other insects) and whilst looking things up for this post I was amazed to discover the the British, Canadian and US armed forces all take the beetles very seriously: I particularly like the US paper on "Entomological terrorism", suggesting that Paederus beetles could be used by an enemy in a direct attack. And the Indian Armed Forces investigated the use of the beetles in chemical warfare back in 2002! Indeed, there's even a suggestion that two of the 10 plagues that the Ancient Egyptian suffered we caused by mass emergence of these beetles that was brough on by the first two (Nile and frogs): Number four (flies), followed a few days later by number 6 (incurable boils).

Paederus crebinpunctatus or P. sabaeus? Anyone know? Arusha, March 2012
That actually leads nicely into what started me puzzling over these beasts in the first place: a beetle crawls on you, you damage it as you brush it away and nothing happens. Huh? Then a day or two later, your skin turns red and soon it starts to blister nastily, the sores lasting (I can say from personal experience!) for 10 days to two weeks. A pretty seriously long time for such a nasty experience. So I set out to research what makes these beetles quite so nasty. As ever, the more I learnt, the more fascinating it becomes. It turns out that the toxin involved is highly toxic - about 15 times more toxic than Cobra venom, (which means that the dose you have to give a group of 100 rats to kill 50 of them is about 1/15th that of cobra venom) so it's just as well they don't bite! And trust me, you really, really don't want to eat one of these beetles. But it's action is far from normal - this isn't an acid burn as some would have you think (in fact, the active ingredient is an amide, so probably slightly alkaline), but something far more interesting. It turns out that whilst we still don't know exactly how it does it, the active ingredient (called pedarin, as it comes from Paederus beetles) has the almost instant effect of stopping the cells making protein and DNA. That might not sound too bad, but over a day or two it's pretty serious (hence the interesting delay in the action) as cells that stop doing these things die (in fact, the cells kill themselves, in a process known as apoptosis).

Now, stopping protein and DNA synthesis (but, curiously, not RNA synthesis) is a pretty remarkable activity for a biological toxin, and like a lot of defence chemicals it's attracted a bit of attention from the pharmaceutical world. One property in particular is very interesting: it stops cell division (mitosis). Now, if you know anything about cancer, you'll know that a cancer is simply a bunch of cells that have forgotten to stop dividing. So a chemical that stops cell division, and can even induce cells to kill themselves is going to attract a lot of interest. And sure enough, pedarin has been shown to slow the growth of a cancerous tumour in mice. I've not found any research yet that takes this further into humans, but watch this space...

Interestingly too, it turns out that pedarin isn't actually produced by the beetles themselves. Only females can produce it themselves (though males can have some from the egg), and only some females at that. In fact, it's produced by symbiotic bacteria living within the insect, a species of bacteria that is fairly closely related to Pseudomonas aeruginosa, a fairly well-known disease causing bug. It turns out that females with the bacteria lay eggs that are also infected with the bacteria, allowing their offspring to be pre-infected with it (though males can't keep it and must make use of the tiny quantities of chemical in the egg). Females without the bacteria can't do this, but they can be infected with it if they eat the eggs or larvae of a female that is infected, and then they, too, can lay eggs pre-infected with the bacteria. Neat! And there's even a theory that squashing the beetle releases not only the beetle juices (technically called haemolymph), but also the bacteria too, which can keep living in the skin for a while, producing yet more nasty pedarin - and explaining quite why it might take so long to heal. As I say, they're really, really nasty bugs!

Main references:

ResearchBlogging.orgKellner, R. (2002). Molecular identification of an endosymbiotic bacterium associated with pederin biosynthesis in Paederus sabaeus (Coleoptera: Staphylinidae) Insect Biochemistry and Molecular Biology, 32 (4), 389-395 DOI: 10.1016/S0965-1748(01)00115-1 

Jewett, J., & Rawal, V. (2007). Total Synthesis of Pederin Angewandte Chemie, 119 (34), 6622-6624 DOI: 10.1002/ange.200701677

Brega, A. (1968). STUDIES ON THE MECHANISM OF ACTION OF PEDERINE The Journal of Cell Biology, 36 (3), 485-496 DOI: 10.1083/jcb.36.3.485

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