Are Antivitamins the New Antibiotics?
Antibiotics are among the most important discoveries of modern medicine and have saved millions of lives since the discovery of penicillin almost 100 years ago. Many diseases caused by bacterial infections – such as pneumonia, meningitis or septicaemia – are successfully treated with antibiotics. However, bacteria can develop resistance to antibiotics which then leaves doctors struggling to find effective treatments.
First author Dr. Rabe von Pappenheim examines protein crystals of a bacterial enzyme that was “poisoned” with an antivitamin.
Credit: Lisa-Marie Funk
Antivitamins are substances that inhibit the biological function of a genuine vitamin. Some antivitamins have a similar chemical structure to those of the actual vitamin whose action they block or restrict. For this study, Professor Kai Tittmann’s team from the Göttingen Center for Molecular Biosciences at the University of Göttingen worked together with Professor Bert de Groot’s group from the Max Planck Institute for Biophysical Chemistry Göttingen and Professor Tadgh Begley from Texas A&M University (USA).
Together they investigated the mechanism of action at the atomic level of a naturally occurring antivitamin of vitamin B1. Some bacteria are able to produce a toxic form of this vital vitamin B1 to kill competing bacteria. This particular antivitamin has only a single atom in addition to the natural vitamin in a seemingly unimportant place and the exciting research question was why the action of the vitamin was still prevented or “poisoned”.
Tittmann’s team used high-resolution protein crystallography to investigate how the antivitamin inhibits an important protein from the central metabolism of bacteria. The researchers found that the “dance of the protons”, which can normally be observed in functioning proteins, almost completely ceases to function and the protein no longer works. “Just one extra atom in the antivitamin acts like a grain of sand in a complex gear system by blocking its finely tuned mechanics,” explains Tittmann. It is interesting to note that human proteins are able to cope relatively well with the antivitamin and continue working.
The research project was funded by the German Research Foundation (DFG).
Contacts and sources:
Professor Kai Tittmann
University of Göttingen
Molecular Enzymology Group
Professor Bert de Groot
Max Planck Institute for Biophysical Chemistry
Computational Biomolecular Dynamics Research Group
Publication: Structural basis for antibiotic action of the B1 antivitamin 2′-methoxy-thiamine. Fabian Rabe von Pappenheim, Matteo Aldeghi, Brateen Shome, Tadhg Begley, Bert L. de Groot, Kai Tittmann. Nature Chemical Biology, 2020; DOI: 10.1038/s41589-020-0628-4
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Whistler Blowers, Insiders
There are functional medicines against most bacteria causing infections. They were invented over 100 years a go, so no profits for corrupt medical establishment. This group of medicines is called sulfonamides, more commonly known as Sulfa medicines. They are so simple to manufacture, that most high school chemistry classes have necessary equipment. Terror strories of antibiotic resistant strains are just propaganda to feed the financial needs of Big Pharma. Your life does not matter, don’t lie to yourself.