(RxWiki News) How a 60-year-old drug used to treat an even older disease, tuberculosis (TB), works has never really been understood, until now. Pyrazinamide (PZA) appears to be a tie that binds TB progression.
Researchers at John Hopkins Bloomberg School of Public Health have discovered that PZA works by ultimately preventing the bacteria from properly ridding itself of waste products.
"Passing the test of time, PZA has been effective treating tuberculosis."
Ying Zhang, M.D., Ph.D., senior author of the study and professor in the Bloomberg School’s W. Harry Feinstone Department of Molecular Microbiology and Immunology reports that PZA is designed differently than most antibiotics that kill growing bacteria. PZA primarily kills non-growing bacteria that aren't treatable with common antibiotics.
Dr. Zhang continues to report that PZA is the stand alone drug that isn't replaceable with new therapies without compromising therapy efficacy. The identification of the target RpsA creates new avenues for improved TB treatments and drug developments.
In the body, PZA is turned into pyrazinoic acid (POA) by an amidase enzyme (PncA). After several experiments, Dr. Zhang and his colleagues were able to determine that POA binds to ribosomal protein S1 (RpsA). This protein inhibits a process called trans-translation that is used by the organism to remove waste products from the cell.
"The identification of the drug target RpsA not only offers a new resistance mechanism to PZA but also opens up a way for designing a new generation of antibiotics that target persister bacteria for improved treatment of chronic and persistent infections including TB,” said Dr. Zhang.
These findings are published in the August 2011 edition of Science Express.