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Foiled Antibiotics

Bacterial resistance to antibiotic medicines is commonplace, is spreading worldwide, and is a major threat to human health.

There are strains of bacteria resistant to every known drug. Don’t catch one of these beasties unless you’re sure your last will and testament is in good order.

The medicinal chemist’s reaction to drug resistance is to create new drugs (in fact, this is the medicinal chemist’s reaction to everything....). To be truly effective, a new drug would act on a new target and not merely be a structural variation on an existing medicine.

One exciting new target for antimicrobials has been fatty acid biosynthesis. Fatty acids are essential components of bacterial membranes, and thus of life. Best of all, the pathway to fatty acid creation is different in bacteria than in humans. Voila, a target that could lead to drugs that kill microbes but leave patients’ own biochemistry untouched.

Nature has even provided a lead compound: platensimycin. It comes from a soil fungus, is a potent inhibitor of fatty acid biosynthesis, and has been the model for development of a whole new class of desperately needed synthetic antibiotics.

Whoops. A new report from a collaborative Parisian group (Nature 458 [March 5, 2009], 83–86) reveals a flaw in the reasoning for this type of antibacterial agent. Sure, if you inhibit fatty acid formation it kills the bacterium. But if the bug has another source of fatty acids, it simply doesn’t care that its own synthetic mechanism is impeded.

Soil doesn’t have a ready source of fatty acids so platensimycin is very effective in that environment. But higher organisms have blood, which is well stocked with fatty acids, and thus such antibiotics just don’t work in real patients (who happen to be rats in this study).

Don’t be too nihilistic about drug development, though. There might be ways to avoid fatty acid uptake by nasty bacteria or to combine such inhibitors with other drugs in a more potent combination.

Never underestimate scientific ingenuity!

Posted In: Policy | Technology

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