Monday, October 17, 2005

ADEPs: A possible new class of antibiotic

Many dangerous bacteria are showing up with resistance to current antibiotics, so new antibiotics are badly needed. Nature Medicine this month talks about an antibiotic substance that attacks bugs in a brand new way. The compounds, ADEPs, act by removing controls on an enzyme in the bacteria which is normally used to dispose of malfunctioning proteins. Without the control, this enzyme becomes hyperactive and attacks even normal proteins-- with the result that the bacteria essentially digest themselves. Since this class of compounds acts differently than current antibiotics, it is unlikely that cross-resistance will be a problem.

The original molecule of this series had been isolated as a naturally produced defense from a bacterial culture. It had been patented in 1985, and then essentially abandoned. The folks at Nature Medicine emphasize that the natural world is likely to continue to be a good source of compounds, and that many new compounds might already be sitting in the patent books.

As terrific as it is that new drugs might be on the way, antibiotics should not be the first line of public health defense. Bugs will inevitably develop resistance to any single compound, which implies a pharmaceutical treadmill in which new compounds are continually needed. Thus, hygiene still matters an awful lot. I have also been very interested in naturally occurring microbial ecosystems in which the various species keep each other in check via mutual inhibition. There is some still literature suggesting that pathogens might also respond to social controls. This approach is interesting to me because the pathogens are not killed, just socialized. What I don't know is how mutants which ignore these controls-- corresponding exactly to an antibiotic resistant clone or a cancer cell-- get dealt with in natural ecosystems.

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