Untangling the mysteries of DNAA unique natural process responsible for packaging DNA in bacteria could prove to be the "Achilles Heel" of harmful disease-causing bugs. Scientists at the John Innes Centre on Norwich Research Park are working on this process, which will hopefully pave the way for better antibiotics. DNA is a long string-like molecule, found in all living things. In fact, there are almost 2 metres of DNA in every cell in our bodies. So how does all this genetic information fit into cells that are less than a tenth of a millimetre across? It must be carefully packaged, by coiling the long DNA strands in a very controlled way. But although the DNA is tightly compacted, it must be accessible enough to allow the DNA code to be read and translated by the cell when needed. This packaging process is so important, that the cell dies if it goes wrong. DNA packaging happens spontaneously in humans. But in bacteria, a protein called DNA gyrase has the crucial job of coiling up the bacterial DNA. So if this DNA gyrase could be somehow inactivated, it could potentially provide a way of killing harmful bacteria. The fact that the protein is found only in bacteria and not humans makes it an ideal target for specific anti-bacterial drugs. At present there are two classes of drug that affect DNA gyrase. One class is the coumarins, which inhibit the action of the gyrase, but don't dissolve very well in water. This makes it difficult for them to be absorbed by the body. The other class is the quinolones. These work by binding to both the bacterial gyrase and to the DNA at the same time. Once bound, they prevent the DNA from being replicated. This ultimately causes the bacteria to die. They are particularly potent, as the binding of a single molecule of the drug to the DNA strand is enough, in principle, to stop the entire process. Quinolones are still effective against most bacterial infections, so are only used sparingly by doctors. This is to try and reduce the number of drug-resistant strains of bacteria which result from over-exposure to antibiotics. A natural consequence of using antibiotics is that bacteria become increasingly resistant. So there is a huge pressure to develop new anti-bacterial drugs. The JIC scientists are looking at the interaction between DNA gyrase and the quinolones more closely to try and learn more about how they bind to each other. Their approach has been to study small isolated regions of the gyrase protein. These regions have been studied using X-rays to determine their structure. The analyses have revealed a potential site where quinolones are predicted to bind to the protein. The next challenge is to work out the structure of the protein with the drug bound to it. This information will help to improve drug targetting to the gyrase, to ensure that it is as specific as possible by only binding to the crucial part of the enzyme. The researchers hope that their work will lead to the development
of novel drugs against bacteria that resist all existing antibiotics.
For example, there is little defence against the MRSA co-called
"super bug" which kills many people each year. The JIC
research offers hope for the control of this potentially deadly
bacterium as well as others that might also become resistant to
current drugs. © Dr Belinda Clarke 2001 This Article originally appeared as part of the "Science on your Doorstep" series, published in the Eastern Daily Press 3rd February 2001
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