NEW YORK (Reuters Health) - Diphosphomevalonate (DPM) binds to a site essential for the survival and virulence of Streptococcus pneumoniae, researchers report in the December 28th issue of Biochemistry.
“The target appears to be a streptococcal-specific adaptation, suggesting that pneumococcus can be inhibited without the risk of developing broad-spectrum antibiotic resistance,” senior investigator Dr. Thomas S. Leyh, of the Albert Einstein College of Medicine in New York, told Reuters Health.
In particular, DPM binds to mevalonate kinase and switches off the pathogen’s mevalonate pathway. However, the investigators established that human mevalonate kinase is not inhibited by DPM.
Thus, continued Dr. Leyh, “we hope to be able to prevent survival of the organism in its native habitat, the lung, without significantly influencing human metabolism.”
In the absence of a functioning mevalonate pathway, the researchers found that the organism “is unable to survive in mouse lung” and “virulence is severely attenuated.”
The DPM-binding site, he concludes, “is a promising target for the development of new antimicrobial agents.” The researchers are now testing five compounds based on the DPM template.
“We’ve discovered a molecular lock and key that can help release us from the confines of this organism,” Dr. Leyh concluded. “We’re currently working on fashioning better keys.”
Source: Biochemistry 2004. [ Google search on this article ]
MeSH Headings:Biological Phenomena: Biological Phenomena, Cell Phenomena, and Immunity: Biological Sciences: Biology: Drug Resistance, Microbial: Genetics: Genetics, Microbial: Microbiologic Phenomena: Pharmacogenetics: Drugs, Investigational: Biological SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
