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Why does an anti-anthrax drug kill plants too?

May 12, 2004

Scientists at the John Innes Centre (JIC), Norwich (1) have today reported that a very successful antibiotic, which is harmless to humans but lethal to most bacteria, also kills plants. They have found that an enzyme, which is an important target for several families of antibiotics and was thought to exist only in bacteria, is also present in plants. The discovery sheds further light on plant evolution and highlights a potential area for development of new herbicides, while it has no significance with regard to the medical use and efficacy of the antibiotic. The discovery is reported online and in the latest volume of the international scientific journal Proceedings of the National Academy of Sciences, USA.

"Our interest is in the structure of DNA and in particular in an enzyme called DNA gyrase(2), which is crucial for maintaining the structure of the DNA molecule in bacteria" says Professor Tony Maxwell (Head of Biological Chemistry at JIC). "The antibiotic ciprofloxacin (Cipro), made famous in 2001 during the anthrax attacks in the US, targets DNA gyrase which, until now, we thought was a bacterial 'Achilles heel' because it had only been found in bacteria. However, we have now discovered that plants are sensitive to Cipro and that is because DNA gyrase is also important in plants".

Working with the common weed Thale Cress (Arabidopsis thaliana) Dr. Melisa Wall, a member of Prof. Maxwell's team at JIC, found DNA gyrase in both the chloroplasts and mitochondria in plant cells. These tiny structures (called organelles) are responsible for carrying out photosynthesis and respiration respectively (3). Scientists think that organelles originated from bacteria that were able to live in plant cells and over evolutionary time they eventually became highly specialised to perform particular functions for the cells they were living in. The fact that the organelles still use DNA gyrase is an echo of their distant past as free-living bacteria.

Plants manage their DNA in a very different way from bacteria and have no use for DNA gyrase. Yet the relationship between the organelles and the plant cell has become so sophisticated and intimate that the genes encoding DNA gyrase are actually present in the DNA molecule of the plant nucleus, not in the organelles themselves. When the DNA gyrase enzyme is produced in the plant cell it is tagged with a fragment of protein that directs it to the appropriate organelle, where it carries out its function of DNA maintenance.

"The discovery that Cipro can kill plants raises the possibility of developing new herbicides based on the structure of Cipro and other drugs that target DNA gyrase" says Dr Wall. "Cipro kills bacteria very effectively but has low animal toxicity. We are now studying the DNA gyrases found in plants and bacteria to see if we can exploit differences between them to selectively kill plants while leaving other organisms, especially bacteria, unaffected".

John Innes Centre