Saturday, 11 July 2009

Erm, does anyone have any new antibitoics?

The golden age of antibiotics is drawing gradually but definitively to an end.

Since Alexander Flemming revoloutionised the way we view diseases with his discovery of penicillin in 1928, we have stopped worryingabout ailments like whooping cough and tuberculosis. It's worth remembering though that pre-1920s these kind of bacterial infections were rife, and wiped out large numbers of people, regularly. Plague epidemics, for example, have occurred several times in the last ten thousand years, with notably widespread outbreaks in the mid 1300s, 1665 ('the great plague of London') and again just before the beginning of the 20th century. There were also localised bouts constantly happening all over the world up until Flemmings' breakthrough.

So we've seemed to have the upper hand on bacteria for the last 100 years or so - but bugs that we can't beat are coming back. For instance, MRSA [1] has been thwarting the efforts of hospital staff to disinfect-it-out-of-existence for a number of years now. Although they're not bactrial (but rather viral) in nature, the SARS [2] and swine flu epidemics are two other examples - rather more immediate and frightening ones - of why we need to sit up and start thinking about whether we are too comfortable with the ways we treat disease.

The problem is that bacteria are very quick to develop resistance to antibiotics. Drugs like penicillin, great 40 or so years ago, quickly became no good at treating a whole host of bacterial infections. So called wide-spectrum antibiotics have been a big problem; they act upon just about any bacteria they meet, so even if all the bacteria which are the source of the problem are destroyed, lots of others will inevitably remain which have had a chance to build up resistance. Up until now we've had reserve drugs, which we only use in emegencies, so bacteria don't have a chnace to develop resistence. Even these though, are beginning to become less effective. It may only be a matter of decades before we no longer have a last line of antibiotic defence. We need new drugs, and quickly.

In science, researchers often look to nature for inspiration, and for this reason it turns out that the majority of the antibiotics in clinical use today are what are called 'natural products'. These are complicated chemicals which float around in all living organisms. Especially interesting ones can be found in single-celled organisms. Typically scientists take one of these cells, (a type known as streptomyces is very popular) and extract some of its bodily fluids and try and identify the various compounds contained in them. This kind of process led to the identification of some of the most powerful antibiotics we know of, such as Vancomycin and Chloramphenicol.

Now its getting progressively more difficult to identify new, useful antibiotics. One way some scientists think we should move forward is to, again, take a quick look at nature and see what we can learn. But this time we need to look in new places.

Recently sceintists have begun to explore in depth a fact which we have known in essence for many years. That is that many species of insect actually use docile bacteria as a protection against the more vicious ones [3]. Storing the organisms in their skin or intestines, or even farming them in the open, insects appear to grow the good bacteria as a protection against the bad. The question is, what compounds are responsible for keeping the bad guys at bay?

Take for example the european Beewolf. Not a bee at all, but an insect which paralyses bees and transports them back, alive, to their sand-burrow nests. There, the imobilised bees are a welcome food source for little beewolf larvae.

The Beewolf - not a bee

The hot sandy burrows are warm and moist - perfect conditions for all types of life, including bacteria. So how is it that the beewolf larvae do so well, apparently immune to the presence of the microorganisms? Researchers have now found that the mature Beewolves smear a sticky white broth containing a previously unencountered type of Streptomyces bacteria all over the cocoons of the developing larvae [4]. The insects and the streptomyces live in a symbiant relationship - the bacteria keep the larvae safe by fighting off infections with their antibiotics, and in return they live off a diet of nice, juicy Bee. Scientists don't yet know what the active compounds the bacteria produce are, but they could prove to be potent antibacterials for human use, too.

Another symbiant partnership exists between leafcutter ants and the common fungus they feed on. The ants carefully farm the fungus, which they use as food. In many parts of the world a highly competitive fungus called Escovopsis out-competes it's fungal enemies. This never happens in ant-farmed funus patches though - why? Again, scientists have been on the trail and have found the ants have been growing bacteria alongside the fungus.

When these new-to-science bacteria were grown in a laboratory, scientists identified a new compound - dentigerumycin - and sure enough, when applied to some Escovopsis it was a potent fungicide.

There are lots more symbiotic insect-microorganism relationships out there which we haven't yet discovered. I'm not suggesting we start coating our young in sticky bacterial broths, but if we continue studying these relationships closely it is easy to imagine a whole host of potential new drugs waiting to be harvested. Then we can keep one step ahead of those pesky mutating bacteria.

Notes and references

[1] MRSA = Methicllin-resistant staphylococcus aureus
[2] SARS = Severe, acute respiratory syndrome
[3] H. B. Bode, Angew. Chem. Int. Ed., 2009, 48, 2 - 5.
[4] M. Kaltenpoth, W. Gttler, G. Herzner, E. Strohm, Curr. Biol. 2005, 15, 475 – 479

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