Do without antibiotics?
Antivitamins can be a substitute for antibiotics
Sergey Vasiliev, Naked Science
For decades, antibiotics have remained a reliable way to fight bacterial infections. Such substances can disrupt the reading of information from their DNA, the synthesis of proteins or cell walls, leading to cell death. However, the ability of bacteria to develop antibiotic resistance mechanisms and then exchange them through horizontal gene transfer threatens to leave us without this beloved weapon.
Outbreaks of infections resistant to the action of various antibiotics are appearing more and more often and already today lead to the death of about 700 thousand people a year. It is not surprising that biologists and doctors around the world are looking for new ways to combat them. One of the promising areas of this work is anti–vitamins, substances that disrupt the body's ability to use vitamins. Antivitamins can destroy them directly or interfere with binding to proteins, preventing them from participating in metabolism.
Today, only three natural anti–vitamins are known - roseoflavin (RoF, anti-vitamin B2), gingkotoxin (GT, anti-vitamin B6) and 2-methioxy-thiamine (MTh, anti-vitamin B1). In a new article published in the journal Nature Chemical Biology (von Pappenheim et al., Structural basis for antibiotic action of the B1 antivitamin 2'-methoxy-thiamine), the mechanism of the latter's work is considered by the example of exposure to human proteins and E. coli.
Using X–ray crystallography, the authors of the work, Kai Tittmann and his colleagues from the University of Göttingen, studied the structures of enzymes involved in vitamin B1 metabolism and found that an additional functional group distinguishing MTh leads to their inactivation when anti–vitamin binds. At the same time, the effect of anti-vitamin B1 on the human enzyme was either completely absent or was not dangerous.
If MTh is able to disrupt the work of a bacterial cell, practically without affecting human cells, then "anti-vitamin" therapy can really become one of the most effective alternatives to antibiotics. "Today it is difficult to predict how and how bacteria could develop resistance to MTh," the scientists add.
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