Penicillin resistance of the bacterium that causes pneumonia, the pneumococcus, is a growing global health problem. Although S. pneumoniae was once considered to be routinely susceptible to penicillin, since the mid-1980s the incidence of resistance of this organism to penicillin and other antimicrobial agents has been increasing in the United States and throughout the world. Now, researchers at The Rockefeller University, reporting in the April 25 issue of the Proceedings of the National Academy of Sciences, show that resistance can be stopped by inactivating a pair of genes responsible for producing molecules called branched muropeptides, the availability of which appears to be essential for the bacterium to survive in the presence of penicillin. The finding suggests that the branched peptides may be a new drug target for fighting penicillin-resistant bacteria.

"We have known for some time about the connection between the branched muropeptides -- structural elements of the pneumococcal cell wall -- and penicillin resistance in pneumococcus," says senior author Alexander Tomasz, Ph.D., professor and head of the Laboratory of Microbiology at Rockefeller. "We have now identified two genes that are responsible for making these branched muropeptides, and we have shown for the first time that by inactivating these genes we can restore penicillin's potency. This opens the door to the development of new drugs that would act synergistically with penicillin by blocking the production of the branched peptides."

S. pneumoniae represents the most important microbial pathogen, causing a number of frequent community-acquired infections, some life threatening. In the United States alone, S. pneumoniae is estimated to cause at least 6,000 cases of meningitis, 50,000 cases of blood infections, a half million cases of pneumonia and several million cases of childhood ear infections annually. The global annual rate of mortality from pneumococcal disease is estimated at o
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Contact: Joseph Bonner
bonnerj@rockvax.rockefefeller.edu
212-327-7900
Rockefeller University
19-Apr-2000