New Class of Antibiotics May Eradicate Pneumonia

A "molecular Achilles heel” in the organism that causes pneumonia provides a target for a new class of antibiotics that could eventually eradicate the disease. The finding is reported in the December 28, 2004, issue of Biochemistry.

The virulence of S pneumoniae requires a properly functioning channel called the isoprenoid biosynthetic pathway. Scientists at the Albert Einstein College of Medicine (New York, NY, USA; www.aecom.yu.edu) have discovered that an intermediate in the pathway called diphosphomevalonate (DPM) can inhibit the pathway enzyme, effectively shutting down the whole process.

"If you switch this pathway off, the organism is in big trouble,” explained lead author Thomas Leyh, Ph.D., a professor of biochemistry at Albert Einstein College of Medicine. Without this channel, the normally pathogenic S pneumoniae is unable to survive in mouse lungs and its virulence is severely weakened.

DPM binds to its own "pocket” on the enzyme, and therefore cannot be dislodged by the enzyme's natural substrates. "Remarkably, the human enzyme is not influenced by the inhibitor,” noted Dr. Leyh. "This means that S pneumoniae in human lungs or blood should be inhibited without any negative effect on human metabolism.”

"Worldwide, the organism takes the lives of some 3,700 people daily, the majority of whom are children below the age of five,” added Dr. Leyh.

The researchers plan to use DPM as a template for developing novel antibiotics to cure pneumonia and other streptococcal diseases, such as meningitis. Dr. Leyh's lab is currently developing and testing five compounds based on the DPM template for their potential as new antibiotics.




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