Antibiotic target signals pneumonia end
causes pneumonia, providing a target for the development of a new
class of antibiotics that could eventually eradicate the disease.
The discovery is all the more important as decades of antibiotic use have produced drug-resistant strains of S. pneumoniae that are capable of evading even last-line-of-defense antibiotics, such as vancomycin.
In the United States alone, roughly 7 million annual cases of inner ear infections caused by this organism saddle the US heath care system with an estimated $5 billion (€3.7 billion) burden.
Scientists diacovered the virulence of S. pneumoniae required a properly functioning channel called the isoprenoid biosynthetic pathway. They discovered that an intermediate in the pathway, diphosphomevalonate, or DPM, can inhibit the first enzyme, effectively shutting down the whole process.
DPM binds to its own "pocket" on the enzyme, and therefore cannot be dislodged by the enzyme's natural substrates. Pharmaceutical companies consider such targets to be among the most important elements in deciding whether or not to pursue a problem.
Thomas Leyh, lead author of the paper said: "If you switch this pathway off, the organism is in big trouble. Without this channel, the normally pathogenic S. pneumoniae is unable to survive in mouse lungs and its virulence is severely attenuated."
"The human enzyme is not influenced by the inhibitor. This means that S. pneumoniae in human lungs or blood should be inhibited without any negative effect on human metabolism."
The researchers plan to use DPM as a template for developing novel antibiotics to cure pneumonia and other streptococcal diseases, such as meningitis. Leyh's lab is currently developing and testing five compounds based on the DPM template for their potential as new antibiotics.
The research is scheduled to appear in the Dec. 28 edition of Biochemistry.
