New antibiotic target could mean the end of pneumonia

Scientists have found a “molecular Achilles heel” in the organism that causes pneumonia, providing a target for the development of a new class of antibiotics that could eventually eradicate the disease. Their report is scheduled to appear in the Dec. 28 edition of Biochemistry, a peer-reviewed journal of the American Chemical Society, the world’s largest scientific society.


“Streptococcus pneumoniae places an enormous burden on the welfare of humanity,” says Thomas Leyh, Ph.D., a professor of biochemistry at the Albert Einstein College of Medicine in New York and lead author of the paper. “Worldwide, the organism takes the lives of some 3,700 people daily, the majority of whom are children below the age of five.”

Decades of antibiotic use have produced drug-resistant strains of S. pneumoniae that are capable of evading even our so-called “last-line-of-defense” antibiotics, such as vancomycin. In the United States alone, the roughly 7 million annual cases of inner ear infections caused by this organism saddle the U.S. heath care system with an estimated $5 billion burden, Leyh says.

The virulence of S. pneumoniae requires a properly functioning channel called the isoprenoid biosynthetic pathway. Leyh and his colleagues have discovered that an intermediate in the pathway — diphosphomevalonate, or DPM — can inhibit the first enzyme, effectively shutting down the whole process. “If you switch this pathway off, the organism is in big trouble,” Leyh says. Without this channel, the normally pathogenic S. pneumoniae is unable to survive in mouse lungs and its virulence is severely attenuated.

“Remarkably, the human enzyme is not influenced by the inhibitor,” Leyh says. This means that S. pneumoniae in human lungs or blood should be inhibited without any negative effect on human metabolism.

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, according to Leyh. “We recognize the need to work with a pharmaceutical partner to bring our basic research discovery to the bedside, and, hopefully, to cure this disease.”

The researchers plan to use DPM as a template for developing novel antibiotics to cure pneumonia and other streptococcal diseases, such as meningitis. “We consider DPM a very powerful lead compound,” Leyh continues. “It’s about as compelling as it can be at this stage.” Leyh’s lab is currently developing and testing five compounds based on the DPM template for their potential as new antibiotics.

The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 159,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio. — Jason Gorss

Media Contact

Michael Bernstein EurekAlert!

More Information:

http://www.acs.org

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Lighting up the future

New multidisciplinary research from the University of St Andrews could lead to more efficient televisions, computer screens and lighting. Researchers at the Organic Semiconductor Centre in the School of Physics and…

Researchers crack sugarcane’s complex genetic code

Sweet success: Scientists created a highly accurate reference genome for one of the most important modern crops and found a rare example of how genes confer disease resistance in plants….

Evolution of the most powerful ocean current on Earth

The Antarctic Circumpolar Current plays an important part in global overturning circulation, the exchange of heat and CO2 between the ocean and atmosphere, and the stability of Antarctica’s ice sheets….

Partners & Sponsors