Saturday, March 3, 2012

New antibiotics to reduce resistance and side effects

It is getting harder and harder to fight off bacterial infections, because of resistance to our antibiotics. Over the years, several bacterial species have become increasingly dangerous, because the drugs we have to fight them have no effect anymore. The call for new antibiotics is therefore getting louder and louder. A research group from St. Jude Children's Research Hospital have made a discovery that could very well lead to the development of new anti-bacterial drugs. This ought to reduce the number of bacterial strains that are hard to kill due to resistance. Moreover, it promises a decrease in side effects.

At St. Jude Children's Research Hospital, scientists investigated a molecule dubbed DHPS, which is important for many bacterial strains. It is an enzyme responsible for the production of folate: an important molecule for the construction of DNA, which is essential for the reproduction of bacteria. Specifically, what the experiments yielded is a clear view of the structure of DHPS, as well as how it works chemically. The researchers used bacterial strains responsible for anthrax and the plague, two nasty diseases which we'd rather be well protected against.
Yersinia pestis: killed many people in medieval times by inducing a disease commonly known as the plague.
In their study, the scientists showed how exactly DHPS propagates the production of folate. It is responsible for fusing two particular molecules, which in turn aid folate synthesis. Actually, the whole process and the associated chemistry is a bit more complex, but the essence of it, is that the active site which DHPS uses to bind to other molecules is now known to us.

Because we now have detailed information about how this particular enzyme works and what it looks like, we can use it to develop new drugs. DHPS inhibitors that target the active site can impede the production of folate, and thus halt the spread of bacteria. Scientists claim this ought to result in less side-effects than conventional antibiotics. Naturally, because we have so far only shown the mechanism, actually getting drugs to the market is going to take a long time. Nevertheless, we are running out of options when it comes to antibiotics, which make these new angles of vital importance for the future of our constant struggle with the microbial world.

It is not the first time DHPS has been targeted as potential antibiotic. So-called sulfa drugs that interact with how this enzyme works were already present 80 years ago. However, detailed molecular data was lacking at that time, which means we were not quite sure what they actually did. Because of resistance to conventional antibiotics, sulfa drugs have regained interest by scientists, and our newfound information can help us create more efficient drugs than those produced 80 years ago. At St. Jude Children's Hospital, they discovered exactly how these sulfa drugs function on a molecular level: this ought to help with improving them. 

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