Antibiotics still count as a miracle of modern science--but one that's fading fast. One by one, the drugs are falling by the wayside as microbes become resistant. In a paper in the 18 may issue of Nature, however, researchers at Merck report having discovered a potent new compound that could give the miracle a new lease on life.
Many antibiotics on the market today work in similar ways: They either paralyze the microbe's ability to build a protective cell wall or prevent the bugs from synthesizing proteins or DNA. These related modes of action mean that microbes that become resistant to one antibiotic often withstand many others as well. The new compound, discovered by a team led by Sheo Singh at Merck Research Laboratories in Rahway, New Jersey, aims for an unusual target: bacterial fatty acid synthesis. Because several enzymes involved in this pathway are highly conserved among pathogenic bacteria, antibiotics directed at them would have the added advantage of attacking a broad range of microbes.
The team's candidate is derived from a fungus called Streptomyces platensis that was recovered from a South African soil sample--one of 83,000 natural extracts screened for antibiotic activity. Dubbed platensimycin, the compound was found to be a potent inhibitor of a whole range of so-called Gram-positive bacteria, including several of the "superbugs" plaguing hospitals, such as Staphylococcus strains resistant to every known antibiotic except vancomycin (ScienceNOW, 14 March 2002). In a mouse model of S. aureus infection, platensimycin wiped out the bacteria efficiently and without apparent toxic side-effects. Structural studies revealed how the drug acts, by binding to FabF, a crucial enzyme in the fatty acid pathway.
Although platensimycin needs to undergo much more testing, including in humans, the discovery is "encouraging," writes microbial chemist Eric Brown of McMaster University in Hamilton, Canada, in an accompanying paper in Nature. That it's in a new league of its own is "particularly exciting," he adds. True, says Stephan Harbarth, an epidemiologist who studies antibiotic resistance at the University of Geneva in Switzerland. But the real problem with antibiotics is their often reckless overuse, which is the root cause of microbial resistance. As long as that problem isn't addressed, Harbarth sides with Dennis Maki of the University of Wisconsin, Madison, who once remarked that developing new antibiotics "is much like supplying your alcoholic patients with a finer brandy."