Bug Zapper: novel drug kills resistant bacteria.A newly recognized compound can wipe out some of the most troublesome antibiotic-resistant bacteria, laboratory tests show. The drug works by sabotaging a microbe's production of fatty acids.
Scientists at Merck Research Laboratories in Rahway, N.J., discovered the compound, which they call platensimycin.
The findings are preliminary but impressive, says Eric D. Brown, a microbiologist at McMaster University in Hamilton, Ontario. "This is a really promising story in a field that has had quite a bit of disappointment," he says.
Roughly 90,000 people in the United States acquire fatal infections in hospitals every year, according to data from the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. in Atlanta. Nearly three-fourths of those deaths can be traced to antibiotic-resistant microbes.
Most antibiotics were developed at least 50 years ago (SN: 5/28/05, p. 327). Those made more recently are almost all variants of the early drugs and work by attacking the bacterial cell wall or DNA- or protein-synthesis machinery.
Merck chemist Sheo B. Singh and his colleagues screened roughly 250,000 natural compounds in search of potent antibacterials. This approach makes sense, Brown says, because organisms in nature "are constantly in warfare with each other." He notes that natural compounds work well as drugs because they target specific weaknesses in rival organisms.
The search led to platensimycin, a small molecule made by the bacterium Streptomyces Streptomyces (strĕp'təmī`sēz), bacterial genus of the order Actinomycetales, members of which resemble fungi in their branching filamentous structure. Various species produce such antibiotics as streptomycin and various tetracyclines. platensis. That bug normally lives in soil in South Africa.
In the May 18 Nature, the researchers report that platensimycin promptly kills lab-dish colonies of staphylococcus staphylococcus (stăf'ələkŏk`əs), any of the pathogenic bacteria, parasitic to humans, that belong to the genus Staphylococcus. The spherical bacterial cells (cocci) typically occur in irregular clusters [Gr. and enterococcus enterococcus /en·tero·coc·cus/ (en?ter-o-kok´us) pl. enterococ´ci an organism belonging to the genus Enterococcus.
Enterococcus /En·tero·coc·cus/ ( bacteria that resist drugs such as vancomycin vancomycin (văn'kōmī`sĭn), antibiotic resembling penicillin in the way it acts. It is derived from the bacterium Streptomyces orientalis, which was isolated from soil of India and Indonesia. and methicillin methicillin /meth·i·cil·lin/ (meth?i-sil´in) a semisynthetic penicillin highly resistant to inactivation by penicillinase; used as the sodium salt.
n. . When the researchers continuously infused mice with the drug in a first test, it killed Staphylococcus aureus Staphylococcus au·re·us
A bacterium that causes furunculosis, pyemia, osteomyelitis, suppuration of wounds, and food poisoning.
Staphylococcus aureus Staphylococcus pyogenes that wasn't drug resistant.
Platensimycin is structurally different from other antibiotics. Unlike most of those drugs, it binds to and neutralizes an enzyme called FabF, which bacteria use to make fatty acids. Platensimycin "preexisted in nature to get this job done," Brown says. "This was pretty good detective work at Merck."
Fatty acids are essential for building and maintaining the membrane that lines the bacterial cell wall. FabF is different from the corresponding enzyme in mammals, suggesting that platensimycin won't inhibit fatty acid synthesis Fatty acids are formed by the action of Fatty acid synthases from acetyl-CoA and malonyl-CoA precursors. In humans fatty acids are predominantly formed in the liver and adipose tissue, and mammary glands during lactation. in people, says Charles O. Rock, a biochemist at St. Jude Children's Research Hospital St. Jude Children's Research Hospital, founded in 1962, is a leading pediatric treatment and research facility focused on children's catastrophic diseases. It is located in Memphis, Tennessee.
In 1996, Peter Doherty, Ph.D., of St. in Memphis, Tenn.
This is the fourth natural compound--and by far the most potent--found to target FabF, Rock notes. "Nature is telling us again and again that if you want to go after bacteria, go after this enzyme," he says.
"If we look long enough and hard enough, we'll find these [fatty acid] inhibitors," says Steven J. Projan, a microbiologist at Wyeth Pharmaceuticals in Cambridge, Mass. But he cautions that the Merck team found it necessary to continuously infuse the drug in the mouse tests. That suggests that platensimycin might be metabolized too quickly in people to make a good drug candidate. Still, the study shows that derailing fatty acid synthesis can kill bacteria, Projan says.
The new finding "just goes to show you how marvelously clever nature is at blocking enzyme activity Enzyme activity
A measure of the ability of an enzyme to catalyze a specific reaction.
Mentioned in: Glucose-6-Phosphate Dehydrogenase Deficiency ," says Brown.
Despite the heady results, the Merck scientists had no comment on whether the company would pursue further development of platensimycin.